Chemfiles Vol. 8, No. 1 - Chemical Ligation

Vol. 8, No. 1

Chemical Ligation

Chemical Ligation by Click Chemistry Native Chemical Ligation Staudinger Ligation Diphenylphosphinemethanethiol: efficacious reagent for traceless Staudinger ligation

Organic Azides and Azide Sources Functionalized Alkynes



Introduction

Vol. 8 No. 1

Introduction

More and more researchers face the task of selectively combining large molecules, attaching molecular probes, or covalently immobilizing substrates on surfaces. In particular when biopolymers and bioconjugates are involved there is an urgent need for mild and biocompatible reaction conditions. A toolbox of several powerful chemical ligation techniques already exists and is continually being expanded. In this issue of ChemFiles, we provide an overview of modern chemical ligation methods and introduce highly innovative and unique new tools for research at the interface between chemistry and biology. The most prominent chemical ligation techniques (click chemistry, native chemical ligation, and Staudinger ligation) will be discussed. A comprehensive listing of available organic azides and functionalized alkynes rounds off this issue of ChemFiles with valuable building blocks for click chemistry or Staudinger ligation. If you are unable to find the specific reagent you need, “Please Bother Us.” with your suggestions at [email protected], or contact your local Sigma-Aldrich® office (see back cover).

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About Our Cover The cover structure depicts diphenylphosphinemethanethiol, the most efficacious reagent known today to induce traceless Staudinger ligations (Raines ligation reagent). Diphenylphosphinemethanethiol can be obtained easily from the shelf-stable precursor 670359 by removing the acetyl and borane protective groups.

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Chemical Ligation by Click Chemistry—A “Click” Away from Discovery The traditional process of drug discovery based on natural secondary metabolites has often been slow, costly, and laborintensive. Even with the advent of combinatorial chemistry and high-throughput screening in the past two decades, the generation of leads is dependent on the reliability of the individual reactions to construct the new molecular framework.

Of the reactions comprising the click universe, the “perfect” example is the Huisgen 1,3-dipolar cycloaddition of alkynes to azides to form 1,4-disubsituted-1,2,3-triazoles (Scheme 1). The copper(I)-catalyzed reaction is mild and very efficient, requiring no protecting groups and no purification in many cases.2 The azide and alkyne functional groups are largely inert towards biological molecules and aqueous environments, which allows the use of the Huisgen 1,3-dipolar cycloaddition in target guided synthesis3 and activity-based protein profiling,4 or the ligation of biopolymers to probes or surfaces.5 For example, Carell and co-workers demonstrated the labelling of alkyne modified DNA oligomers with fluorescence probes by click chemistry.6 The triazole has similarities to the ubiquitous amide moiety found in nature. Thus triazole formation was used for the otherwise difficult macrocyclization of a cyclic tetrapeptide analog to a potent tyrosinase inhibitor.7 Additionally triazoles are nearly impossible to oxidize or reduce. This is a main reason why material science has discovered Huisgen cycloadditions as major ligation tools in diverse areas such as polymer science or nanoelectronics.8 Using Cu(II) salts with ascorbate has been the method of choice for the preparative synthesis of 1,2,3-triazoles, but it is problematic in bioconjugation applications. However, tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine, TBTA (Figure 1), has been shown to effectively enhance the copper-catalyzed cycloaddition without damaging biological scaffolds.9

N N N R1

R2

1 mol% CuSO4 5 mol% sodium ascorbate H2O/tBuOH 2:1 rt, 8 h

N

N

A new reagent developed by Carolyn R. Bertozzi and co-workers eliminates the toxicity to living cells that is usually associated with the copper catalyzed Huisgen 1,3-dipolar cycloaddition.11 By using a difluorinated cyclooctyne (Figure 3) instead of the usual terminal alkyne a rapid cycloaddition reaction takes place even without a catalyst. The ring strain and the electron-withdrawing difluoro group activate the alkyne for copper-free click chemistry. This method was used to attach fluorescent labels to cells with azidecontaining sialic acid in their surface glycans. Thus, it was possible to study the dynamics of glycan trafficking in living cells over the course of 24 hours with no indication that the reaction or the labels perturb the process. This is an impressive example of how copper-free click chemistry can be used as a biologically friendly method to label and track biomolecules in living cells. Sigma-Aldrich® proudly offers a choice of catalysts and ligands for the Huisgen cycloaddition reaction. Later sections in this issue present a comprehensive overview of available organic azides, azide sources, and alkynes that may be applied in click chemistry. If you want to learn about hot new product additions to the click chemistry universe and other innovative areas of chemical synthesis as soon as they become available, please check our regularly updated product highlights at sigma-aldrich.com/ chemicalsynthesis. References: (1) For recent reviews, see: (a) Kolb, H. C.; Sharpless, K. B. Drug Discovery Today 2003, 8, 1128. (b) Kolb, H. C. et al. Angew. Chem. Int. Ed. 2001, 40, 2004. (2)(a) Rostovtsev, V. V.; Green, L.G.; Fokin, V.V.; Sharpless, K.B. Angew. Chem. Int. Ed. 2002, 41, 2596. (b) Tornøe, C. W. et al. J. Org. Chem. 2002, 67, 3057. (3)(a) Manetsch, R. et al. J. Am. Chem. Soc. 2004, 126, 12809. (b) Lewis, W.G. et al. Angew. Chem. Int. Ed. 2002, 41, 1053. (4) Speers, A. E. J. Am. Chem. Soc. 2003, 125, 4686. (5) Wolfbeis, O.S. Angew. Chem. Int. Ed. 2007, 46, 2980. (6) Gierlich, J.; Burley, G.A.; Gramlich, P.M.E.; Hammond, D.M.; Carell, T. Org. Lett. 2006, 8, 3639. (7) Bock, V.D.; Perciaccente, R.; Jansen, T.P.; Hiemstra, H.; Maarseveen, J.H. Org. Lett. 2006, 8, 919. (8) Lutz, J.-F. Angew. Chem. Int. Ed. 2007, 46, 1018. (9) Chan, T.R. et al. Org. Lett 2004, 6, 2853. (10) Rodionov, V. O.; Presolski, S. I.; Gardinier, S.; Lim, Y.-H.; Finn, M. G. J. Am. Chem. Soc. 2007, 129, 12696. (11) Baskin, J.M.; Prescher, J.A.; Laughlin, S.T.; Agard, N.J.; Chang, P.V.; Miller, I.A.; Lo, A.; Codelli, J.A.; Bertozzi, C.R. PNAS 2007, 104, 16793.

2 N R

1

R

Scheme 1

N

R N

N R R = H or -(CH2)4CO2K

N N R

N N N N N N

N N

Figure 2

N R

N N N

O N H

F F

R = fluorescent dye or biotin

Figure 1

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Figure 3

Chemical Ligation by Click Chemistry

Click chemistry is a newer approach to the synthesis of druglike molecules that can accelerate the drug discovery process by utilizing a few practical and reliable reactions. Sharpless and co-workers have defined what makes a click reaction: one that is wide in scope and easy to perform, uses only readily available reagents, and is insensitive to oxygen and water. In fact, water is in several instances the ideal reaction solvent, providing the best yields and highest rates. Reaction work-up and purification uses benign solvents and avoids chromatography.1

In an extensive study Finn and co-workers only recently showed that tris(2-benzimidazolylmethyl)amines (general structure in Figure 2) are the most promising family of accelerating ligands for the Cu catalyzed azide-alkyne cycloaddition reaction from among more than 100 mono-, bi-, and polydentate candidates.10 Under both preparative (high concentration, low catalyst loading) and dilute (lower substrate concentration, higher catalyst loading) conditions, these tripodal benzimidazole derivatives give substantial improvements in rate and yields, with convenient workup to remove residual Cu and ligand.



Click Catalysts and Ligands

Chloro(penta­methyl­cyclo­penta­dienyl)(cyclo­octa­- diene)ruthe­nium(II)

Copper(II) acetate, 98% Cupric acetate C4H6CuO4 FW 181.63 [142‑71‑2]

C18H27ClRu FW 379.93

O H3C

O

CH3 H3C

CH3 CH3

H3C

Cu2+

Cl Ru

2

667234-250MG

326755-25G

25 g

326755-100G

100 g

Copper(I) bro­mide, 98%

Chemical Ligation by Click Chemistry

8

Cuprous bro­mide BrCu FW 143.45 [7787‑70‑4]

CuBr

212865-50G

50 g

212865-250G

250 g

212865-1KG

1 kg

Copper(I) iodide, 98%

250 mg

667234-1G

1 g

Penta­methyl­cyclo­penta­dienyl­bis(tri­phenyl­phos­phine)ruthe­nium(II) chloride Chloro(penta­methyl­cyclo­penta­dienyl)bis(tri­phenyl­phos- ­phine)ruthe­nium(II) C46H45ClP2Ru FW 796.32 [92361‑49‑4]

CH3 H3C

CH3

Ru CH3 Ph3P Cl PPh3

H3C

673293-250MG

250 mg

673293-1G

1 g

(+)-Sodium L-ascorbate, ≥98%

Cuprous iodide CuI FW 190.45 [7681‑65‑4]

CuI

L(+)-Ascorbic

acid sodium salt; Vitamin C sodium salt

C6H7NaO6 FW 198.11 [134‑03‑2]

HO O

ONa OH

O OH

205540-50G

50 g

A7631-25G

25 g

205540-250G

250 g

A7631-100G

100 g

1 kg

A7631-500G

500 g

205540-1KG

A7631-1KG

Copper(II) sulfate, ≥99% Cupric sulfate CuO4S FW 159.61 [7758‑98‑7]

CuSO4

Tenta­Gel™ TBTA Tris[(1-benzyl-1H-1,2,3- triazol-4-yl)methyl]amine, poly­mer bound

C1297-100G

100 g

C1297-500G

500 g

Copper(II) sulfate pentahydrate, ≥98.0% Cupric sulfate pentahydrate CuO4S · 5H2O FW 249.69 [7758‑99‑8] 98.0-102.0% (ACS specification) 209198-5G

1 kg 8 N N N N N N

H N

N N N N

O

696773-250MG CuSO4 • 5H2O

250 mg

Tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine, 97% TBTA C30H30N10 FW 530.63

N N N N N N N

5 g

209198-100G

100 g

209198-250G

250 g

209198-500G

500 g

209198-2.5KG

2.5 kg

N N N

678937-50MG

50 mg

678937-500MG

500 mg

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Native Chemical Ligation Introduction: Chemical Synthesis of Peptides and Proteins Despite competition by recombinant DNA techniques, the synthetic preparation of peptides and proteins offers approaches to protein engineering that are beyond the realm of biology and the limitations of the genetic code. Unlike nature, purely synthetic methods allow the design of peptides entirely from scratch and the furnishing of protein analogs with virtually any unnatural residue.

The development of chemoselective reactions to give a native peptide bond at the site of ligation allows the synthesis of proteins by joining smaller peptides synthesized previously by SPPS. The challenge of this approach is to form an amide bond chemoselectively in the presence of amino acid side chains presenting free amines (Lys) and carboxylates (Glu/Asp). Ideally, no protecting groups should be used and all chemical transformations should take place under mild conditions that are compatible with biological environments. The most powerful technique of this kind is Native Chemical Ligation (NCL) that was introduced by Kent and co-workers in 1994 (Scheme 1).12 Prior to this work, Wieland had observed the condensation of peptide thioesters in early, pioneering investigations.13 Meanwhile, Native Chemical Ligation has enabled the synthesis of many moderate-size proteins and glycoproteins, culminating in the assembly of a 203 amino acid HIV protease covalent dimer.14 Some innovative applications and improved procedures for NCL will be presented later in this chapter. Expressed Protein Ligation (EPL) finally combines the strengths of molecular biology and chemical synthesis by filling the gap between chemistry and biology. A protein expressed by recombinant DNA techniques can be extended with synthetic peptide fragments post-translationally. In recent examples, Cole and co-workers used EPL for the C-terminal attachment of a small phosphorylated synthetic peptide.15 Waldmann, Goody, and co-workers demonstrated the EPL synthesis of an azide-modified N-Ras protein and its site-specific immobilization onto a phosphinefunctionalized glass surface by means of the Staudinger ligation.16

References: (12) Dawson, P.E.; Muir, T.W.; Clark-Lewis, I.; Kent, S.B.H. Science, 1994, 266, 776. (13) Wieland, T.; Bokelmann, E.; Bauer, L.; Lang, H.U.; Lau, H. Justus Liebigs Ann. Chem. 1953, 583, 129. (14) Torbeev, V.Y.; Kent, S.B.H. Angew Chem. Int. Ed. 2007, 46, 1667. (15) Cole, P.A. J. Am. Chem. Soc. 2006, 128, 4192. (16) Watzke, A. et al. Angew. Chem. Int. Ed. 2006, 45, 1408. (17) Johnson, E.C.B.; Kent, S.B.H. J. Am. Chem. Soc. 2006, 128, 6640. (18) Yan, L.Z.; Dawson, P.E. J. Am. Chem. Soc. 2001, 123, 526. (19) Pentelute, B.L.; Kent, S.B.H. Org. Lett. 2007, 9, 687.

� Solution-phase peptide synthesis Only small peptides (chain length < 10 aa) � Solid-phase peptide synthesis Medium sized peptides (chain length < 50 aa) � Native chemical ligation Peptides and smaller proteins (chain length < 200 aa) � Expressed protein ligation Chemically modified proteins (chain length > 500 aa) � Staudinger ligation Modification, immobilization, or combination of peptides Figure 1 SH

O 1

peptide

SR

+

H2N

peptide1

S

peptide2 NH2

SH

O peptide1

N H

peptide2

Scheme 1

Native Chemical Ligation

Native Chemical Ligation allows the combination of two unprotected peptide segments by the reaction of a α-thioester with a cysteine-peptide (Scheme 1). The result of this reaction is a native amide bond at the ligation site, rendering this method highly attractive for the synthesis of large peptides. Usually, α-alkylthioesters are used because of their ease of preparation. Since they are rather unreactive, the ligation reaction is catalyzed by in situ transthioesterification with thiol additives. The most common thiol catalysts to date have been either a mixture of thiophenyl/benzyl mercaptan, or 2-mercaptoethanesulfonate (MESNa). In a recent study, it was shown that MESNa is a poor catalyst, requiring reaction times of typically 24–48 hours. It is outperformed by far by certain aryl thiols. Using 4-mercaptophenylacetic acid (MPAA), proteins can be synthesized much more rapidly (Figure 2). Chemical ligations are typically complete in less than an hour and with high yields.17

O

peptide2

HS

O ONa S O MESNa

OH O

HS

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MPAA

Figure 2

Native Chemical Ligation

Chemical peptide synthesis faces certain limitations though. Solution-phase synthesis methods are suitable for peptides with a chain length of up to ten amino acids (Figure 1). Solid-phase peptide synthesis (SPPS) broadens the range of accessible peptides by dramatically enhancing speed and efficiency of the synthesis. Still the maximum chain length of the peptides prepared by SPPS is limited to about 50 amino acid residues.

Native chemical ligation usually relies on the location of suitable Xaa–Cys ligation sites, spaced at intervals no greater than about 40 residues in the target amino acid sequence. However, Xaa–Cys sites in a protein’s polypeptide chain are often limiting: Cys residues are rare or even absent in many proteins, or only present in an unsuitable position. Yan and Dawson introduced an approach that allows Xaa–Ala ligation sites, with a Cys residue used in place of the native Ala residue. Subsequent desulfurization of the ligation product with freshly prepared Raney nickel produces the native target sequence.18 Recently, this methodology has been extended by Kent and co-workers to the synthesis of Cys-containing peptides by ligating fragments at Xaa–Ala junctions.19 Using acetamidomethyl (Acm) side chain protecting groups for Cys residues other than the ligation site, efficient and selective desulfurization of the ligation site is feasible.



4-Mer­capto­phenyl­acetic acid, 97%

Fmoc-Cys(Acm)-OH, ≥95.0% (HPLC, sum of enantiomers)

653152-1G

1 g

Nα-Fmoc-S-acet­amino­methyl-L-cys­teine C21H22N2O5S FW 414.47 [86060‑81‑3]

653152-5G

5 g

47603-5G

C8H8O2S FW 168.21 [39161‑84‑7]

OH O

HS

Native Chemical Ligation

O S ONa

HS

Nα-Fmoc-S-acet­amino­methyl-L-cys­teine 4-benzyl­oxy­benzyl ester poly­mer-bound

50 g

S-Acet­amido­methyl-L-cys­teine 2-chloro­trityl ester poly­mer-bound 94399-1G-F

TentaGel S PHB-Cys(Acm)Fmoc

O S

• HCl OH

CH3

Fmoc

H-Cys(Acm)-2-ClTrt resin

H-Cys(Acm).HCl C6H12N2O3S · HCl FW 228.70 [28798‑28‑9]

1 g

Nα-Fmoc-S-acet­amido­methyl-L-cys­teine 4-[poly(ethyl­enoxy)]benzyl ester poly­mer-bound

NH2

00320-1G

1 g

86383-5G

5 g

Boc-Cys(Acm)-PAM resin

Boc-Cys(Acm)-OH, ≥96.0% (T)

15376-5G

N H

1 g

S-Acet­amido­methyl-L-cys­teine hydrochloride, ≥99.0% (AT) O

Fmoc

O S

47613-1G-F 10 g

Boc-S-acet­amido­methyl-L-cys­teine C11H20N2O5S FW 292.35 [19746‑37‑3]

OH HN

O HN

63705-50G

N H

S

5 g

O

63705-10G

H3C

O N H

Fmoc-Cys(Acm)-Wang resin

Sodium 2-mer­capto­ethane­sulfo­nate, ≥98.0% (RT) Coenzyme M sodium salt; HS-CoM Na; 2-Mer­capto­ethane­sulfonic acid sodium salt; MESNA C2H5NaO3S2 FW 164.18 [19767‑45‑4]

O H3C

O H3C

Boc-S-(acet­amido­methyl)-L-cys­teine bound to PAM resin

O N H

S

OH HN

61254-1G-F

1 g

Boc

5 g

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Staudinger Ligation

The phosphine reagent can be synthesized from aminoterephthalic acid methyl ester by diazotization, followed by iodination and subsequent Pd-catalyzed phosphinylation (Scheme 4).

Introduction

Staudinger and Meyer first reported in 1919 that azides react smoothly with triaryl phosphines to form iminophosphoranes after elimination of nitrogen (Scheme 1).21 This imination reaction proceeds under mild conditions, almost quantitatively, and without noticeable formation of any side products. The resulting iminophosphorane with its highly nucleophilic nitrogen atom can also be regarded as an aza-ylide (Scheme 2). It may be intercepted with almost any kind of electrophilic reagent. Common pathways include aqueous hydrolysis forming a primary amine and a phosphine(V) oxide in the so-called Staudinger reduction. Quenching with aldehydes or ketones yields imines, which is known as the aza-Wittig reaction. Even carbonyl electrophiles with low reactivity, like amides or esters, react with iminophosphoranes, especially if the reaction can take place intramolecularly (Scheme 3).

The free acid moiety allows the easy attachment of a wide choice of molecular probes to the phosphine reagent by standard esterification or amidation procedures. Thus, a fluorescence label or different detection probe can be linked to any biomolecule that has been equipped with an azide function by the Staudinger ligation even in living cells (Scheme 5). The following paragraph shows how GlycoProfile™ azido sugars can be incorporated into glycan structures in vivo, and be used to attach a FLAG® phosphine probe chemically.

H3CO

O

1) NaNO2 HCl/H2O 2) KI, H2O

NH2

H3CO

O I

Pd(OAc)2 (1%) Ph2PH Et3N, MeOH

57 % O

OH

PPh2

OH

O

650064

H3CO

O

O

OH

Scheme 4

target PPh2

O

69 % O

393673

H3CO

O

target

HN

O PPh2

N N N

O

O

probe

O probe

Scheme 5

References: (20) Köhn, M.; Breinbauer, R. Angew. Chem. Int. Ed. 2004, 43, 3106. (21) Staudinger, H.; Meyer, J. Helv. Chim. Acta 1919, 2, 635. (22) Saxon, E.; Bertozzi, C.R. Science 2000, 287, 2007.

P

+

P

N N N

1-Methyl 2-iodo­tere­phthal­ate, 90%

+ N2

N

Scheme 1

C9H7IO4 FW 306.05

O OCH3 HO

I O

N R'

R3P

R3P

N R'

Scheme 2

650064-1G

1 g

650064-10G

10 g

1-Methyl-2-amino­tere­phthal­ate, 98% H N R1 H

2

R

O H 2O

R2

N R1

C9H9NO4 FW 195.17 [60728‑41‑8]

R3

R3

O OCH3 HO

NH2 O

R R P N 1 R R R2

R2 N C O - R3PO R2 N C N R1

O N H

R3

R2

N R

Nontraceless Staudinger Ligation

5 g

393673-25G

25 g

2-(Diphenyl­phos­phino)tere­phthal­ic acid, 1-methyl 4-penta­fluoro­phenyl­di­ester, 97%

1

HN R3

393673-5G

Scheme 3

Bertozzi et al. pioneered the application of the Staudinger reaction as a ligation method for bioconjugates. In the course of their studies on the metabolic engineering of cell surfaces they designed a phosphine with an ester moiety as an intramolecular electrophilic trap. After formation of the iminophosphorane from the newly designed phosphine reagent and an azide, the ester moiety captures the aza-ylide in a fast intramolecular cyclization reaction before hydrolysis with water can occur. This process ultimately produces a stable amide bond.22

1-Methyl-4-(penta­fluoro­phenyl)-2-(diphenyl­- phos­phino)-1,4-ben­zene­dicarboxy­late C27H16F5O4P FW 530.38

O F F

OCH3 O

F

F

P O

F

679011-25MG

25 mg

679011-100MG

100 mg

2-(Diphenyl­phos­phino)benzoic acid, 97% C19H15O2P FW 306.30 [17261‑28‑8]

O OH P

454885-1G

1 g

454885-5G

5 g

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Staudinger Ligation

The reaction between an azide and a phosphine forming an aza-ylide was discovered almost a century ago by Nobel Prize laureate Herrmann Staudinger. It has found widespread application in chemical synthesis, but only recently its value as a highly chemoselective ligation method for the preparation of bioconjugates has been recognized.20 Both reactive functionalities involved in this reaction are bioorthogonal to virtually all naturally existing functionalities in biological systems and readily combine at room temperature tolerating an aqueous environment. These ideal conditions make it possible to exploit the Staudinger ligation even in the complex environment of living cells.



Staudinger Ligation

GlycoProfile™ Azido Sugars

N-Azido­acetyl­manno­s­amine, Acetyl­ated

The GlycoProfile™ Azido Sugar portfolio consists of three peracetylated azido sugars that may be incorporated into glycan structures chemically or by using existing biosynthetic pathways of mammalian cells.23 Orthogonally to chemical and biological carbohydrate or peptide synthesis, the azide moiety offers an ideal anchor to attach the modified glycan to surfaces, labels, peptides, or proteins. Labelling even works in vivo by using an alternative metabolic-system approach. The acetyl groups increase cell permeability and allow the unnatural sugars to easily pass through the cell membrane. Carboxyesterases remove the acetyl groups once the monosaccharide is in the cell. Cells metabolize the azido sugars using glycosyltransferases and express the sugars on the terminus of a glycan chain both intracelullarly and on the cell surface, leaving the azido group unreacted. N-Azidoacetylmannosamine may also be introduced into the sialic acid biosynthesis pathway. A phosphine probe containing a detection epitope such as the FLAG® peptide can be selectively bound to the glycan by Staudinger Ligation, resulting in a post-translationally modified glycoprotein that is detected in vivo by using a FLAG®-specific antibody. This approach permits the analysis of pathways that are regulated by particular glycan post-translational modifications as well as the monitoring of the intracellular glycosylation process itself.

8

ManNaz C16H22N4O10 FW 430.37

O RO OR

N3

HN O

O

OR

RO

R=*

CH3

A7605-1MG

1 mg

A7605-5MG

5 mg

N-Azido­acetyl­galacto­s­amine, Acetyl­ated

8

GalNaz C16H22N4O10 FW 430.37

O

OR

RO

OR

R=*

O

CH3

OR

HN

N3 O

A7480-1MG

1 mg

A7480-5MG

5 mg

N-Azido­acetyl­gluco­s­amine, Acetyl­ated GlcNaz C16H22N4O10 FW 430.37

8 RO OR RO

O

O

OR R=*

HN

CH3

N3 O

OAc

AcO

O OAc

AcO

GalNAz

A7355-1MG

1 mg

A7355-5MG

5 mg

NH N3 O

Metabolic labeling AcO

cell

OAc O

AcO O NH N3 O O

Staudinger ligation

FLAG

..

R

O

CH3

P

Puzzled by Glycobiology?

FLAG-Phosphine R

AcO

OAc O

AcO O

NH

FLAG

P

The Glycobiology Analysis Manual is a must-have reference guide for the fields of glycoproteomics and glycomics. The Manual features:

NH

O

R

O

O

Labeled glycoprotein

Profiling O-type glycoproteins by metabolic labeling with an azido GalNAc analog (GalNAz) followed by Staudinger ligation with a phosphine probe (FLAG-phosphine). Reference: (23)(a) Saxon, E.; Bertozzi, C. R. Science 2000, 287, 2007. (b) Saxon, E.; Bertozzi, C. R. Annu. Rev. Cell. Dev. Biol. 2001, 17, 1. (c) Bertozzi, C. R.; Kiessling, L. L. Science 2001, 291, 2357. (d) Dube, D. H.; Prescher, J. A.; Quang, C. N.; Bertozzi, C. R. Proc. Natl. Acad. Sci 2006, 103, 4819.

Glyco­Profile FLAG–Phos­phine conjugate N-[4-Carbo­methoxy-3-(diphenyl­phos­phino) benzoyl]-Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Lys C62H75N10O23P FW 1359.29

GPHOS1-1MG GPHOS1-5X1MG

8

• Updated and expanded technical content

Glycobiology Analysis Manual 2nd edition

• Structural and functional reviews

Whether you are an expert in carbohydrate biology and chemistry or just getting started in glycomics, the Glycobiology Analysis Manual provides the products and methods you need to solve your glycomics puzzle! Q

Q

Tools for Glycop roteomics and Glycom ics

O OCH3

DYKDDDK

• Innovative products and kits

P

1 mg 5 × 1 mg

Q

Q

Glycan Labeling and

Analysis

Glycoprotein Purification and Detection

Chemical and Enzymatic Deglycosylation

Enzymatic Synthesis and Degradation

Visit sigma.com/glycomanual and request your copy.

sigma-aldrich.com

TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit sigma-aldrich.com/chemicalsynthesis.



Traceless Staudinger Ligation

Although the previously described methods for Staudinger ligations work well even in biological environments, a modification forming a native amide bond without leaving the unnatural phosphine oxide moiety in the product would be more attractive yet. In 2000, the groups of Bertozzi and Raines simultaneously introduced alternative ligation strategies.24 Based on the same working principle as the nontraceless Staudinger Ligation the auxiliary phosphine reagent can be cleaved from the product after the ligation is completed leaving a native amide bond. Thus, the total chemical synthesis of proteins and glycopeptides is enabled overcoming the limitations of native chemical ligation (NCL) of a Cys residue at the ligation juncture.

HS

Figure 1 O R1

Most recently, Raines and co-workers introduced a water-soluble variant of their reagent carrying dimethylamino groups (Figure 2). This substrate mediates the rapid ligation of equimolar substrates in water. In a pilot experiment, traceless Staudinger ligation was integrated with expressed protein ligation (EPL), revealing future opportunities in modern protein chemistry.29 References: (24)(a) Saxon, E.; Armstrong, C.R.; Bertozzi, C.R. Org. Lett. 2000, 2, 2141. (b) Nilsson, B.L.; Kiessling, L.L.; Raines, R.T. Org. Lett. 2000, 2, 1939. (25) Soellner, M.B.; Nilsson, B.L.; Raines, R.T. J. Am. Chem. Soc. 2006, 128, 8820. (26) Kleineweischede, R.; Jaradat, D.; Hackenberger, P.R. Contributions at the 8th German Peptide Symposium 2007, Heidelberg, Germany. (27) David, O.; Meester, W.J.N.; Bieräugel, H.; Schoemaker, H.E.; Hiemstra, H.; van Maarseveen, J.H. Angew. Chem. Int. Ed. 2003, 42, 4373. (28) Liu, L.; Hong, Y.-Y., Wong, C.-H. ChemBioChem 2006, 7, 429. (29) Tam, A.; Soellner, M.B.; Raines, R.T. J. Am. Chem. Soc. 2007, 129, 11421.

+

HS

R1

PPh2

S

PPh2

O R1

O

N H

670359 BH3 S

PPh2

O

H 2O

R2

- HSCH2POPh2

HS

rt, 95%

S

P+Ph2 -N 2 R

Scheme 6

BH3

NaOMe, MeOH

PPh2 1) 95% TFA, 1 h 2) DIPEA, rt 95%

®

DABCO toluene, 40 °C 95% O

R1

NaOH, MeOH S

PPh2

HS

94%

PPh2

Scheme 7

HS PH+ H+ N

H+ N

x 3 Cl-

Figure 2

Acetyl­thio­methyl-diphenyl­phos­phine borane com­plex, ≥98.0% C15H18BOPS FW 288.15 [446822‑71‑5]

670359-250MG

8

O H3B P

S

CH3

250 mg

670359-1G

1g

1,4-Diaza­bicyclo[2.2.2]octane, 98% DABCO; TED; Tri­ethylene­di­amine C6H12N2 FW 112.17 [280‑57‑9]

N N

D27802-25G

25 g

D27802-100G

100 g

D27802-500G

500 g

D27802-2KG

2 kg

1,4-Diaza­bicyclo[2.2.2]octane hydro­chloride, poly­mer-bound Dabco chloride resin; TED-Cl resin

N N

Cl

578282-5G

5 g

578282-25G

25 g

Dabco 33-LV 1,4-Diaza­bicyclo[2.2.2]octane solution C6H12N2 FW 112.17 [280‑57‑9]

N N

290734-100ML

100 mL

290734-500ML

500 mL

Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com.

Staudinger Ligation

Other Staudinger ligation induced macrocyclizations have been published previously by Maarseveen and co-workers, who successfully used the Raines ligation reagent for the synthesis of a series of medium-sized lactams.27 Wong and co-workers reported the synthesis of 14 different glycopeptides through the traceless Staudinger Ligation.28 For this work, they also developed a protease-catalyzed method to selectively introduce an N-terminal azido group into an unprotected polypeptide, as it was needed for the subsequent ligation reaction.

O SR'

N3 R2

Among the suitable phosphine reagents for traceless Staudinger ligations, diphenylphosphinemethanethiol (Figure 1), developed by Raines and co-workers, exhibits the best reactivity profile and has already found widespread application. This Raines ligation reagent is first acylated. Treatment with an azide leads to the formation of an aza-ylide. The nucleophilic nitrogen atom of the aza-ylide then attacks the carbonyl group, cleaving the thioester. Hydrolysis of the rearranged product finally produces a native amide and liberates the auxiliary as its phosphine(V) oxide (Scheme 6).25 It’s recommended to use a freshly prepared Raines ligation reagent because it has only a limited stability. In this issue of ChemFiles, Sigma-Aldrich® proudly introduces new product 670359 as a shelf-stable, convenient source for this highly useful reagent (sold under license for research and development purposes only. U.S. Patent 6,974,884 and related patents apply). In the acetylthiomethyldiphenylphosphine borane complex 670359, the thiol and phosphine moiety are protected as acetyl ester and borane adduct, respectively. The active Raines ligation reagent can be liberated easily by treatment with DABCO® at 40 °C followed by basic ester cleavage (Scheme 7). Hackenberger and co-workers showed that acidic deprotection of the phosphine-borane was advantageous in glycopeptide and cyclopeptide preparations.26 In the latter case, a linear peptide with terminal azide and phosphine-borane groups was synthesized by SPPS. 95% TFA was used to deprotect the phosphine and the amino acid side chains simultaneously in a single step. Diisopropylethylamine (DIPEA) was then added to trigger the peptide macrocyclization by traceless Staudinger ligation, yielding cyclic Microcin J25 with 21 amino acids.

P

10

Organic Azides and Azide Sources

Azido­tris(diethyl­amino)phos­pho­nium bro­mide

Organic Azides and Azide Sources

Since the preparation of the first organic azide, phenyl azide, by Peter Griess in 1864 this energy-rich and versatile class of compounds has enjoyed considerable interest. In more recent years, completely new perspectives have emerged, notably the use of organic azides for peptide synthesis, combinatorial synthesis, heterocycle synthesis, and the ligation or modification of biopolymers.30 The most prominent fields of application today are Huisgen 1,3-dipolar cycloadditions, and different variants of the Staudinger ligation. The azido group can also be regarded as a protecting group for coordinating primary amines, especially in sensitive substrates like complex carbohydrates or peptidonucleic acids (PNA).31 For example, it is stable to alkene metathesis conditions.32

References: (30) Bräse, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew. Chem. Int. Ed. 2005, 44, 5188. (31) Debaene, F.; Winssinger, N. Org. Lett. 2003, 5, 4445. (32) Kanemitsu, T.; Seeberger, P.H. Org. Lett. 2003, 5, 4541. (33) Waser, J.; Nambu, H.; Carreira, E.M. J. Am. Chem. Soc. 2005, 127, 8294.

t-Bu +

R'

TsN3

N3

CH3

11556-1G

1 g

11556-5G

5 g

 98% 380822-1G

1 g

Ben­zene­sul­fonyl azide, functionalized silica gel O S N3 O

5 g

Ben­zene­sul­fonyl azide, poly­mer-bound O S N3 O

572977-5G

5 g

4-Carboxy­ben­zene­sulfo­nazide, 97% 4-(Azido­sul­fonyl)benzoic acid C7H5N3O4S FW 227.20 [17202‑49‑2]

O S N3 O

HO O

340138-2.5G

2.5 g

Cesium azide, 99.99%

N

510181-5G

5 g

510181-25G

25 g

CO2K

6 mol%

R''

R

CsN3

Cobalt(II) tetra­fluoro­borate hexahydrate, 99%

R' N3

Scheme 1

Azide Sources

B2CoF8 · 6H2O FW 340.63 [15684‑35‑2]



Co(BF4)2 • 6H2O

399957-25G

25 g

399957-100G

100 g

Diphenyl phos­phor­yl azide

4-Acet­amido­ben­zene­sul­fonyl azide, 97% O S N3 O

O H3C

N H

404764-5G

5 g

404764-25G

25 g

Azide exchange resin,azide on Amberlite IRA-400 368342-10G

10 g

368342-50G

50 g

DPPA; Phos­phor­ic acid diphenyl ester azide C12H10N3O3P FW 275.20 [26386‑88‑9]

O O P O N3

 97% 178756-5G

5 g

178756-25G

25 g

178756-100G

100 g

 ≥90% (HPLC) 79627-50ML

50 mL

Diphenyl­phos­phor­yl azide, poly­mer-bound

Azido­tri­methyl­silane, 95% Tri­methyl­silyl azide C3H9N3Si FW 115.21 [4648‑54‑8]

H3C

Ph Ph

6 mol% Co(BF4)2 · 6 H2O 30 mol% t-BuOOH, silane EtOH, 23 °C, 2-24 h

p-ABSA C8H8N4O3S FW 240.24 [2158‑14‑7]

CH3

CsN3 FW 174.93 [22750‑57‑8]

OH

R''

 ≥97.0% (AT)

Br

N N P N

590274-5G

An elegant way to produce organic azides from unactivated olefins was recently reported by Carreira and co-workers. A catalyst, that is easily prepared from Co(BF4)2 · 6H2O and a Schiff base, allows hydroazidation with p-toluenesulfonyl azide (TsN3) to yield alkyl azides. Mono-, di-, and trisubstituted olefins are tolerated in this reaction, and complete Markovnikov selectivity is observed (Scheme 1).33

R

CH3 CH3 H3C

Si

Sigma-Aldrich® is offering a broad range of organic azides for your research. Additionally a wide choice of azide sources facilitates the preparation of tailor-made organic azides.

t-Bu

C12H30BrN6P FW 369.28 [130888‑29‑8]

CH3

DPPA poly­mer-bound; PS-DPPA

H3C Si N3

O O P O

CH3

N3

668168-1G

1 g

155071-10G

10 g

668168-5G

5 g

155071-50G

50 g

668168-25G

25 g

Azido­tri­methyl­tin(IV), 97%

Lithium azide solution

C3H11N3Sn FW 207.85 [1118‑03‑2]

LiN3 FW 48.96 [19597‑69‑4]

349488-1G

1 g

349488-5G

5 g

LiN3

 20 wt. % in H2O 480525-25G

25 g

480525-100G

100 g

TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit sigma-aldrich.com/chemicalsynthesis.

11

Potas­sium 2-(3,5-di-tert-butyl-2-hydroxy­benzyl­idene­amino)2,2-diphenyl­acetate, 95% Potas­sium N-(3,5-di-tert-butyl­salicyl­idene)-2- amino-2,2-diphenyl­acetate C29H32KNO3 FW 481.67

H3C H3C

CH3 OK

N O

OH H3C

250 mg

676551-1G

2-Azido-2-methyl­pro­pionic acid C4H7N3O2 FW 129.12 [2654‑97‑9]

O H3C H3C

OH N3

 ~15% in heptane (T)

CH3 CH3

676551-250MG

α-Azido­iso­butyric acid solution

1 g

52916-10ML-F

10 mL

52916-50ML-F

50 mL

 ~15% in heptane (T) 59955-10ML-F

N3Na FW 65.01 [26628‑22‑8]

NaN3

 99.99+% (metals basis) 438456-5G

5 g

438456-25G

25 g

 ≥99.0% (T) 71290-10G

10 g

71290-100G

100 g

71290-500G

500 g

 ≥99% 13412-100G-R

100 g

13412-6X100G-R

6 × 100 g

13412-250G-R

250 g

13412-1KG-R

1 kg

13412-6X1KG-R

6 × 1 kg

13412-20KG-R

20 kg

Tetra­butyl­ammo­nium azide C16H36N4 FW 284.48 [993‑22‑6]

CH3

H3C

10 mL

Azido­methyl phenyl sulfide, 95% Phenyl­thio­methyl azide C7H7N3S FW 165.22 [77422‑70‑9]

S

N3

244546-1G

1 g

6-(4-Azido-2-nitro­phenyl­amino)hexanoic acid N-hydroxy­succini­mide ester, ≥90% N-Succini­midyl 6-(4-azido- 2-nitro­ani­lino)hexa­noate C16H18N6O6 FW 390.35 [64309‑05‑3]

O

N3

O2N

O

N O

N H

O

A3407-50MG

50 mg

(2S,3R,4E)-2-Azido-4-octa­decene-1,3-diol D-Sphingosine

azide

OH

C18H35N3O2 FW 325.49 [103348‑49‑8]

CH(CH2)12CH3

HO N3

N3-

A0456-1MG

1 mg

A0456-5MG

5 mg

651664-5G

5 g

4-Azido­phen­acyl bro­mide

651664-25G

25 g

N CH3

H3C

Organic Azides 1-Azido­ada­man­tane, 97% N3

C10H15N3 FW 177.25 [24886‑73‑5]

1 g

276219-5G

5 g

4-Azido­ani­line hydrochloride, 97% 4-Amino­phenyl azide hydrochloride C6H6N4 · HCl FW 170.60 [91159‑79‑4]

NH2 • HCl N3

Br N3

A6057-500MG

500 mg

11550-250MG-F

250 mg

11550-1G-F

1 g

4-Azido­phenyl iso­thio­cyanate, 97% C7H4N4S FW 176.20 [74261‑65‑7]

NCS N3

359564-500MG

359556-250MG

250 mg

359556-1G

1 g

(4S)-4-[(1R)-2-Azido-1-(benzyl­oxy)ethyl]-2,2-dimethyl-1,3dioxolane C14H19N3O3 FW 277.32

C21H18N6O FW 370.41 [5284‑79‑7]

O

N3

N3 CH3

283029-5G

O

5 g

 ≥90% (HPLC, calc. based on dry substance)

O

14528-10G

H3C CH3

573213-1G

1 g

[3aS-(3aα,4α,5β,7aα)]-5-Azido-7-bromo-3a,4,5,7a-tetra­hydro-2,2-dimethyl-1,3-benzo­dioxol-4-ol, 99%

10 g

4,4’-Diazido-2,2’-stil­bene­disulfonic acid disodium salt hydrate, 97% C14H8N6Na2O6S2 · xH2O FW 466.36 (Anh)

Br O O

N3

500 mg

2,6-Bis(4-azido­benzyl­idene)-4-methyl­cyclo­hexan­one

 97%

N3 O

CH3 CH3

OH

493406-500MG

O

 ≥98.0% (HPLC)

276219-1G

C9H12BrN3O3 FW 290.11 [171916‑75‑9]

4’-Azido-2-bromo­aceto­phen­one; 4-Azido- α-bromo­aceto­phen­one C8H6BrN3O FW 240.06 [57018‑46‑9]

SO3– Na+

N3

363227-10G

500 mg

Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com.

N3 • xH2O SO3– Na+

10 g

Organic Azides and Azide Sources

Sodium azide

12

7-(Diethyl­amino)cou­marin-3-carbo­nyl azide, ≥95% (HPLC) C14H14N4O3 FW 286.29 [157673‑16‑0]

O-(2-Amino­ethyl)-O′-(2-azido­ethyl)nona­ethylene glycol, ≥90% (oligomer purity)

O N3 H3C

N

O

O CH3

31755-25MG

25 mg

Organic Azides and Azide Sources

Ethi­dium bro­mide mono­azide, ≥95% (HPLC) 3-Amino-8-azido-5-ethyl-6-phenyl­phenan­thridi­nium bro­mide; Ethi­dium mono­azide bro­mide C21H18BrN5 FW 420.31 [58880‑05‑0] E2028-5MG

5 mg

O N3

CH3

O

 ~30% in methylene chloride (NMR) 88539-50ML-F

50 mL

 ~25% in toluene (NMR) 25 mL

 ~25% in ethanol (NMR) 93528-25ML-F

25 mL

4-Methoxy­benzyl­oxy­carbo­nyl azide, 95% 4-Methoxy­benzyl azido­formate C9H9N3O3 FW 207.19 [25474‑85‑5]

O O

N3

H3CO

152854-5G

5 g

152854-25G

25 g

Photo­bio­tin acetate Bio­tin {3-[3-(4-azido-2-nitro­ani­lino)-N-methyl­pro­pyl­amino]pro­pyl­ amide} acetate; N-(4-Azido-2-nitro­phenyl)-N’-(3-bio­tin­yl­amino­pro­pyl)N’-methyl-1,3-propane­di­amine acetate C23H35N9O4S · C2H4O2 O O FW 593.70 HO CH3 HN NH [96087‑38‑6] O2 N

CH3 N

H N

H

H N

H

S

O

N3

79728-1MG

56385-1MG-F

N3

500 mg

O-(2-Amino­ethyl)-O′-(2-azido­ethyl)penta­ethylene glycol, ≥90% (oligomer purity) Azido-PEG-amine (n=6) C14H30N4O6 FW 350.41

O

H2N

6

76172-500MG-F

N3

500 mg

Azido-PEG-acid (n=8) C22H42N4O12 FW 554.59 [846549‑37‑9]

O HO

O

N

HO

8 N3

O

71613-500MG-F

500 mg

Ethyl 8-azido-6-dihydro-5-methyl-6-oxo- 4H-imidazo[1,5-a][1,4]benzo­diazepin­e3-carboxy­late C15H14N6O3 FW 326.31 [91917‑65‑6]

1-Amino-11-azido-3,6,9-tri­oxa­undec­ane; O-(2-Aminoethyl)-O’-(2azidoethyl)diethyl­ene glycol; 2-{2-[2-(2- O O Azidoethoxy)ethoxy]ethoxy}ethylamine H2 N O C8H18N4O3 FW 218.25 [134179‑38‑7]

1 mL

17758-5ML

5 mL

Azido Carbohydrates 2-Acet­amido-2-deoxy-β-D-gluco­pyran­osyl azide 3,4,6- tri­acetate, ≥98.0% (HPLC) 2-Acet­amido-3,4,6-tri-O-acetyl-2-deoxy-β-D- gluco­pyran­osyl azide [6205‑69‑2]

RO OR RO

O

N

N3 O

CH3

CH3 O

671118-250MG

250 mg 1 g

2-Acet­amido-3,4,6-tri-O-benzyl-2-deoxy-β-D- gluco­pyran­osyl azide, ≥98.0% (HPLC)

1 mg

C29H32N4O5 FW 516.59 [214467‑60‑4]

8

RO OR

O

N3 R=*

RO CH3 O

O

CH3

671215-100MG

100 mg

8-Azido­adeno­sine 3′:5′-cyclic mono­phos­phate, ~95%

CH3

R109-25MG

25 mg

R109-100MG

O R=*

HN

O

N

8

N3

HN N

N3

17758-1ML

1 mg

Ro 15-4513

100 mg

C10H11N8O6P FW 370.22 [31966‑52‑6]

NH2 N

N N O

O O P OH

PEG Azides

H2N

N3

N

OH

O

A1262-5MG

O-(2-Amino­ethyl)-O′-(2-azido­ethyl)hepta­ethylene glycol, ≥90% (oligomer purity)

76318-500MG-F

77787-500MG-F

671118-1G

 ≥98.0% (TLC)

Azido-PEG-amine (n=8) C18H38N4O8 FW 438.52 [857891‑82‑8]

10

11-Azido-3,6,9-tri­oxa­un­deca­n-1-amine, ≥90% (GC)

77213-25ML-F

 ≥95% (HPLC)

O

H2N

O-(2-Azido­ethyl)-O-[2-(di­glycolyl-amino)ethyl]hepta­ethylene glycol, ≥90% (oligomer purity)

Ethyl azido­acetate solution C4H7N3O2 FW 129.12 [637‑81‑0]

Azido-PEG-amine (n=10) C22H46N4O10 FW 526.62 [912849‑73‑1]

5 mg

8-Azido-cyclic adeno­sine di­phos­phate-ribo­se, ≥95% (HPLC)

O 8

N3

Cyclic adeno­sine di­phos­phate-ribo­se 8-azide C15H20N8O13P2 FW 582.31 [150424‑94‑5] HO

500 mg

OH OH

O O P O P OH O

NH N

N

O O

N

N

N3

O OH OH

A6830-.1MG

TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit sigma-aldrich.com/chemicalsynthesis.

0.1 mg

13

3′-Azido-2′,3′-dideoxy­uridine, ≥98% (TLC)

1-Azido-1-deoxy-β-D-galacto­pyrano­side, 97% C6H11N3O5 FW 205.17 [35899‑89‑9]

HO HO OH

O

N3

C9H11N5O4 FW 253.21 [84472‑85‑5]

O HN O O

HO

OH

513989-500MG

500 mg A4810-10MG

1-Azido-1-deoxy-β-D-galacto­pyrano­side tetra­acetate, 97% C14H19N3O9 FW 373.32 [13992‑26‑2]

10 mg

N-Azido­acetyl­galacto­s­amine, Acetyl­ated

RO RO OR

O

N3

O R= *

CH3

513970-1G

8

GalNaz C16H22N4O10 FW 430.37

O

OR

RO

1 g

R=*

O

OR

HN

N3

1-Azido-1-deoxy-β-D-gluco­pyrano­side

O

C6H11N3O5 FW 205.17 [20379‑59‑3]

HO OH HO

O

N3

OH

514004-500MG

500 mg

1-Azido-1-deoxy-β-D-gluco­pyrano­side tetra­acetate C14H19N3O9 FW 373.32 [13992‑25‑1]

A7480-1MG

1 mg

A7480-5MG

5 mg

N-Azido­acetyl­gluco­s­amine, Acetyl­ated GlcNaz C16H22N4O10 FW 430.37

8 RO OR

RO OR

O

N3

CH3

N3 O

CH3

A7355-1MG

1 mg

A7355-5MG

513997-1G

1 g

1-Azido-1-deoxy-β-D-lacto­pyrano­side, 97% HO HO

OH

HO OH

O

O

O

N3

514012-500MG

OH

500 mg

3′-Azido-3′-deoxy­thymi­dine O CH3

HN O O

HO

5 mg

N-Azido­acetyl­manno­s­amine, Acetyl­ated ManNaz C16H22N4O10 FW 430.37

8 O RO

HN O

OR

N3 O

OR

RO

OH

R=*

1 mg

A7605-5MG

5 mg

1-O-tert-Butyl­dimethyl­silyl 2-azido-2-deoxy-β-Dgluco­pyrano­side 3,4,6-tri­acetate, 97% C18H31N3O8Si FW 445.54 [99049‑65‑7]

H3C O

H3C

O O

H3C

N

O

O O

CH3 CH3 O Si CH3 CH3 CH3

N3

O

510947-1G

A2169-25MG

25 mg

A2169-100MG

100 mg

A2169-250MG

250 mg

A2169-1G

1 g

1 g

α-D-Manno­pyran­osyl azide, ≥90% (TLC) C6H11N3O5 FW 205.17

HO O OH HO

 ≥99.0% (HPLC)

HO

11546-100MG

100 mg

11546-500MG

500 mg

N3

M6691-100MG

100 mg

α-D-Manno­pyran­osyl azide tetra­acetate, ≥90% (TLC)

2′-Azido-2′-deoxy­uridine, ≥98.0% (N) C9H11N5O5 FW 269.21 [26929‑65‑7]

O HN HO

O O

N

2,3,4,6-Tetra-O-acetyl-α-D-manno­pyran­osyl azide C14H19N3O9 FW 373.32

RO O

O OR RO

RO

R= *

11544-5MG

5 mg

3-Azido-2,3-dideoxy-1-O-(tert-butyl­dimethyl­silyl)β-D-ara­bino-hexo­pyran­ose, 98% CH3

HO N3

O

CH3 CH3 CH3 CH3

O Si

OH

497029-250MG

250 mg

100 mg

2,3,4-Tri-O-acetyl-β-D-xylo­pyran­osyl azide, ≥98.0% (HPLC) C11H15N3O7 FW 301.25 [53784‑33‑1]

CH3

N3

G4168-100MG OH N3

C12H25N3O4Si FW 303.43 [189454‑43‑1]

CH3

A7605-1MG

N3

 ≥98% (HPLC)

O

OR

HN

O R= *

OR

C12H21N3O10 FW 367.31 [69266‑16‑6]

O

R=*

RO

RO

AZT; Azido­thymi­dine C10H13N5O4 FW 267.24 [30516‑87‑1]

CH3

OR

8 O H3C H3C

O O

O

O

N3

O

CH3 O

670790-1G

1 g

670790-5G

5 g

Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com.

Organic Azides and Azide Sources

OR

N

N3

14

Functionalized Alkynes

[(1,1-Dimethyl-2-pro­pyn­yl)oxy]tri­methyl­silane, 98%

Functionalized Alkynes

Alkynes contain a highly versatile functional group that may be utilized for numerous reactions such as electrophilic additions of hydrogen, halogens, hydrogen halides, or water; metathesis; hydroboration; oxidative cleavage; C–C coupling; and cycloadditions. Terminal alkynes may be transformed into metal acetylides and can then be submitted to nucleophilic substitution with alkyl halides, forming new C–C bonds, or nucleophilic addition, e.g., the Favorskii reaction. Sigma-Aldrich® furnishes a broad portfolio of alkynes consisting of more than 250 products. To see the full listing, please visit the organic building blocks section on Chem Product Central at: sigma-aldrich.com/chemprod. From the class of cycloaddition reactions that can be performed with alkynes, the Huisgen 1,3-dipolar cycloaddition stands out and has found tremendous interest in recent years as the best representative of a “click” reaction. Alkyne building blocks with a second functionality are particularly useful in click chemistry. The second functional group allows the attachment of a molecule of interest that subsequently can be “clicked” conveniently to the target azide. The following product list contains alkynes with a free or protected hydroxyl functional group, halogen-bearing alkynes, and miscellaneous other alkynes with an additional functional group.

tert-Butyl­dimethyl(2-pro­pyn­yloxy)silane, 97% C9H18OSi FW 170.32 [76782‑82‑6]

CH3 CH 3 O Si

HC

CH3

CH3 CH3

495492-5ML

5 mL

495492-25ML

25 mL

495239-5ML

5 mL

495239-25ML

25 mL

1,1-Diphenyl-2-pro­pyn-1-ol, 99% C15H12O FW 208.26 [3923‑52‑2]

CH HO C

477443-5G

5 g

477443-25G

25 g

2-Ethynyl­benzyl alcohol, 97% C9H8O FW 132.16 [10602‑08‑1]

OH CH

520039-5G

5 g

4-Ethynyl­benzyl alcohol, 97% C9H8O FW 132.16 [10602‑04‑7]

CH HO

519235-5G

5 g

C8H12O FW 124.18 [78‑27‑3]

OH CH

E51406-5ML

5 mL

E51406-100ML

100 mL

E51406-5L

5 L

E51406-20L

20 L

1-Ethynyl­cyclo­penta­nol, 98%

2-tert-Butyl­dimethyl­siloxy­but-3-yne, 97% tert-Butyl-dimethyl-(methyl-prop-2-ynloxy)silane

CH3 Si

O

HC

CH3

CH3

CH3 CH3 CH3

667579-1G

1 g

667579-10G

10 g

4-(tert-Butyl­dimethyl­silyl­oxy)-1-butyne, 97% CH3 CH3 O Si CH3 CH3 CH3

HC

541672-5ML

5 mL

541672-25ML

25 mL

3-Butyn-1-ol, 97% C4H6O FW 70.09 [927‑74‑2]

OH

HC

130850-5G

5 g

130850-25G

25 g

130850-100G

100 g

3-Butyn-2-ol, 97% C4H6O FW 70.09 [2028‑63‑9]

OH HC CH3

447986-25ML

25 mL

447986-100ML

100 mL

3,5-Dimethyl-1-hexyn-3-ol, 99% C8H14O FW 126.20 [107‑54‑0]

CH3 O Si CH3 CH3 CH3

H3C HC

1-Ethynyl-1-cyclo­hexanol, ≥99%

Hydroxylated Alkynes

C10H20OSi FW 184.35 [78592‑82‑2]

C8H16OSi FW 156.30 [17869‑77‑1]

OH HC

CH3

CH3 CH3

278394-100ML

100 mL

278394-500ML

500 mL

C7H10O FW 110.15 [17356‑19‑3]

OH CH

130869-5G

5 g

2-(3-Fluoro­phenyl)-3-butyn-2-ol, 90% C10H9FO FW 164.18

CH3 CH OH F

648930-1G

1 g

1-Heptyn-3-ol, 97% C7H12O FW 112.17 [7383‑19‑9]

CH3

HC OH

666963-1G

1 g

666963-10G

10 g

1-Hexyn-3-ol, 90% C6H10O FW 98.14 [105‑31‑7]

CH3

HC OH

537764-5G

5 g

537764-25G

25 g

5-Hexyn-1-ol, 96% C6H10O FW 98.14 [928‑90‑5] 302015-1G

HC

OH

1 g

302015-5G

5 g

302015-25G

25 g

TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit sigma-aldrich.com/chemicalsynthesis.

15

3-Hydroxy­phenyl­acetyl­ene

2-Phenyl-3-butyn-2-ol, ≥98%

3-Ethynyl­phenol C8H6O FW 118.13 [10401‑11‑3]

CH HO

C10H10O FW 146.19 [127‑66‑2]

CH3 CH OH

212997-5G

5 g

632023-1G

1 g

212997-25G

25 g

632023-5G

5 g

212997-100G

100 g

2-Methyl-3-butyn-2-ol, 98%

1-Phenyl-2-pro­pyn-1-ol, 98% CH3 OH CH3

HC

129763-5ML

5 mL

129763-100ML

100 mL

129763-1L

1 L

5-Methyl-1-hexyn-3-ol, 97% C7H12O FW 112.17 [61996‑79‑0]

CH3

HC

OH CH3

666971-1G

1 g

666971-5G

5 g

HO CH

226610-1G

1 g

226610-10G

10 g

Pro­pargyl alcohol, 99% 2-Pro­pyn-1-ol C3H4O FW 56.06 [107‑19‑7]

HC OH

P50803-5ML

3-Methyl-1-penten-4-yn-3-ol, 98% Ethynyl methyl vinyl carbinol C6H8O FW 96.13 [3230‑69‑1]

HO HC

CH2 CH3

5 mL

P50803-100ML

100 mL

P50803-500ML

500 mL

P50803-1L

1 L

1,1,1-Tri­fluoro-2-phenyl-3-butyn-2-ol, 96%

493023-5G

5 g

3-Methyl-1-pentyn-3-ol, 98% Ethyl ethynyl methyl carbinol; Meparfynol C6H10O FW 98.14 [77‑75‑8]

HO HC

CH3 CH3

C10H7F3O FW 200.16 [99727‑20‑5]

CF3 CH OH

553298-500MG

500 mg

553298-1G

1 g

3-Tri­methyl­siloxy-1-pro­pyn­e, 98%

137561-100ML

100 mL

137561-500ML

500 mL

1-Octyn-3-ol, 96% C8H14O FW 126.20 [818‑72‑4]

(±)-α-Ethynyl­benzyl alcohol; (±)-3-Hydroxy-3-phenyl-1- pro­pyn­e; 1-Phenyl­pro­pargyl alcohol; (±)-1-Phenyl-2pro­pyn-1-ol C9H8O FW 132.16 [4187‑87‑5]

OH HC

CH3

(Pro­pargyl­oxy)tri­methyl­silane; Tri­methyl(pro­pargyl­oxy) silane; Tri­methyl(2-pro­pyn­yloxy)silane; O-(Tri­methyl­silyl)pro­pargyl alcohol C6H12OSi FW 128.24 [5582‑62‑7]

HC

CH3 O Si CH3 CH3

374423-1G

1 g

10 g

374423-10G

10 g

127280-50G

50 g

127280-250G

250 g

3-(Tri­methyl­silyl­oxy)-1-butyne, 97%

127280-10G

1-Pentyn-3-ol, 98% C5H8O FW 84.12 [4187‑86‑4]

HC

CH3 OH

E28404-1G

1 g

E28404-10G

10 g

4-Pentyn-1-ol, 97% C5H8O FW 84.12 [5390‑04‑5]

OH

HC

2-(Tri­methyl­silyl­oxy)-3-butyne C7H14OSi FW 142.27 [17869‑76‑0]

5 g

302481-25G

25 g

5 g

632031-25G

25 g

10-Undecyn-1-ol, ≥95.0% (GC) C11H20O FW 168.28 [2774‑84‑7]

4-Pentyn-2-ol, ≥98% (±)-4-Pentyn-2-ol C5H8O FW 84.12 [2117‑11‑5] 268992-1G

OH HC

CH3

1 g

268992-5G

5 g

268992-25G

25 g

CH3 O Si CH3 CH3 CH3

632031-5G

94195-1ML

302481-5G

HC

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HC

OH

1 mL

Functionalized Alkynes

Dimethyl ethynyl carbinol C5H8O FW 84.12 [115‑19‑5]

16

Halogenated Alkynes

3-Chloro-1-ethynyl­ben­zene, 97%

(3,5-Bis(tri­fluoro­methyl)phenyl­ethynyl)tri­methyl­silane, 97% C13H12F6Si FW 310.31 [618092‑28‑7]

F3C

CH3 Si CH3 CH3

F3C

597805-5G

Functionalized Alkynes

H3C

Br

1 g 5 g

1-Bromo-2-ethynyl­ben­zene, 95% CH

1 g

1-Bromo-4-ethynyl­ben­zene, 97% Br

CH

206512-1G

1 g

1-Bromo-2-pentyne, 97% C5H7Br FW 147.01 [16400‑32‑1]

Br H3C

429538-1G

1 g

429538-10G

10 g

(2-Bromo­phenyl­ethynyl)tri­methyl­silane, 98% C11H13BrSi FW 253.21 [38274‑16‑7]

Br

CH3 Si CH3 CH3

484695-5G

5 g

(3-Bromo­phenyl­ethynyl)tri­methyl­silane, 97% C11H13BrSi FW 253.21 [3989‑13‑7]

469777-5ML

5 mL

469777-25ML

25 mL

3-Chloro-3-methyl-1-butyne, 97% C5H7Cl FW 102.56 [1111‑97‑3]

HC

CH3 Cl CH3

1 g

301345-5G

5 g

301345-25G

25 g

CH3

Br

5 g

(4-Bromo­phenyl­ethynyl)tri­methyl­silane, 98% CH3 Si CH3 CH3

Br

494011-5G

5 g

494011-25G

25 g

1-Chloro-2-ethynyl­ben­zene, 98% (2-Chloro­phenyl)acetyl­ene C8H5Cl FW 136.58 [873‑31‑4]

CH Cl

Cl

CH3(CH2)3CH2

442860-1G

1 g

442860-10G

10 g

5-Chloro-1-pentyne, 98% C5H7Cl FW 102.56 [14267‑92‑6]

Cl

HC

244376-5G

5 g

244376-25G

25 g

(5-Chloro-1-pentynyl)tri­methyl­silyl­silane, 97% 1-Chloro-5-tri­methyl­silyl-4-pentyne C8H15ClSi FW 174.74 [77113‑48‑5]

CH3 Si CH3

Cl

CH3

5 g

1-Chloro-4-(phenyl­ethynyl)ben­zene, 98% C14H9Cl FW 212.67 [5172‑02‑1]

Cl

510750-1G

1 g

510750-5G

5 g

(3-Chloro­phenyl­ethynyl)tri­methyl­silane, 98% C11H13ClSi FW 208.76 [227936‑62‑1]

CH3 Si CH3 CH3

Cl

597708-1G

1 g

597708-5G

5 g

(4-Chloro­phenyl­ethynyl)tri­methyl­silane, 97%

465305-1G

1 g

465305-5G

5 g

1-Chloro-4-ethynyl­ben­zene, 98% Cl

C8H13Cl FW 144.64 [51575‑83‑8]

595918-5G

CH3 Si CH3

510971-5G

206474-1G

Cl

1-Chloro-2-octyne, 98%

C8H5Br FW 181.03 [766‑96‑1]

(4-Chloro­phenyl)acetyl­ene C8H5Cl FW 136.58 [873‑73‑4]

HC

301345-1G

Br

494178-1G

C11H13BrSi FW 253.21 [16116‑78‑2]

5 g

C6H9Cl FW 116.59 [10297‑06‑0]

427292-5G

C8H5Br FW 181.03 [766‑46‑1]

1 g

630268-5G

6-Chloro-1-hexyne, 98%

427292-1G

CH Cl

630268-1G

5 g

1-Bromo-2-butyne, 99% C4H5Br FW 132.99 [3355‑28‑0]

C8H5Cl FW 136.58 [766‑83‑6]

CH

1 g

C11H13ClSi FW 208.76 [78704‑49‑1]

CH3 Si CH3

Cl

CH3

563447-5G

5 g

563447-25G

25 g

1,4-Dichloro-2-butyne, 99% C4H4Cl2 FW 122.98 [821‑10‑3]

Cl Cl

D59607-5G

5 g

D59607-25G

25 g

D59607-100G

100 g

TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit sigma-aldrich.com/chemicalsynthesis.

17

1-Ethynyl-2-fluoro­ben­zene, 97%

3,4-Dichloro­phenyl­acetyl­ene, 97% 1,2-Dichloro-4-ethynyl­ben­zene; 3,4-Dichloro- 1-ethynyl­ben­zene C8H4Cl2 FW 171.02 [556112‑20‑0]

Cl

CH Cl

250 mg

467006-1G 1 g

(2,4-Difluoro­phenyl­ethynyl)tri­methyl­silane, 96% CH3 Si CH3

F

CH3

563471-5ML

5 mL

(3,5-Difluoro­phenyl­ethynyl)tri­methyl­silane, 98% CH3

F

589330-5G

C8H5F FW 120.12 [766‑98‑3]

F

CH

1 g

404330-5G

5 g

CH F3C

1 g

1-Ethynyl-2,4-difluoro­ben­zene, 97% CH F

556440-5G

1-Ethynyl-4-fluoro­ben­zene, 99%

4-Ethynyl-1-fluoro-2-methyl­ben­zene, 97% C9H7F FW 134.15 [351002‑93‑2]

F

5 g

404330-1G

F3C

630241-1G

CH F

CH3

1-Ethynyl-3,5-bis(tri­fluoro­methyl)ben­zene, 97%

C8H4F2 FW 138.11 [302912‑34‑1]

C8H5F FW 120.12 [2561‑17‑3]

Si CH3

5 g

C10H4F6 FW 238.13 [88444‑81‑9]

1-Ethynyl-3-fluoro­ben­zene, 98%

519405-5G

1 mL

F

1 g

5 g

H3C F

CH

521205-1G

1 g

521205-5G

5 g

2-Ethynyl-α,α,α-tri­fluoro­tolu­ene, 97% 1-Ethynyl-2-tri­fluoro­methyl­ben­zene C9H5F3 FW 170.13 [704‑41‑6]

CH CF3

521183-1G

1 g

3-Ethynyl-α,α,α-tri­fluoro­tolu­ene, 97%

1-Ethynyl-3,5-difluoro­ben­zene, 97% C8H4F2 FW 138.11 [151361‑87‑4]

F CH

CH F3C

557331-5G

F

590177-1G

C9H5F3 FW 170.13 [705‑28‑2]

1 g

Now Available! The New ISOTEC® 2008–2010 Stable Isotopes Catalog from Aldrich Chemistry • • • • •

More than 750 new products Over 3,000 chemical listings 13 C, 15N, D, 18O, 17O labeled products Enriched noble gases Application sections and literature references

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5 g

Functionalized Alkynes

F

563471-1ML

C11H12F2Si FW 210.30 [445491‑09‑8]

CH F

467006-250MG

672890-1G

C11H12F2Si FW 210.30 [480438‑92‑4]

C8H5F FW 120.12 [766‑49‑4]

18

1-[(Tri­methyl­silyl)ethynyl]-4-(tri­fluoro­methyl)ben­zene, 97%

4-Ethynyl-α,α,α-tri­fluoro­tolu­ene, 97% C9H5F3 FW 170.13 [705‑31‑7]

F3C

CH

556432-5G

5 g

(2-Fluoro­phenyl­ethynyl)tri­methyl­silane, 96%

Functionalized Alkynes

C11H13FSi FW 192.30 [480439‑33‑6]

CH3 Si CH3 CH3

F

571407-5G

5 g

571407-25G

25 g

F

5 mL 25 mL

(4-Iodo­phenyl­ethynyl)tri­methyl­silane, 97% Si CH3 CH3

640751-1G

1 g

640751-5G

5 g

Pro­pargyl bro­mide solution 3-Bromo-1-pro­pyn­e C3H3Br FW 118.96 [106‑96‑7]

HC Br

CH3

H N

HC

CH3

H3C CH3 CH3

5 g

N-tert-Butyl-1,1-dimethyl­pro­pargyl­amine, 97% C9H17N FW 139.24 [1118‑17‑8]

HC

H N

CH3 CH3 H3C CH3 CH3

5 g

Cyclo­pro­pyl­acetyl­ene, 97% Ethynyl­cyclo­propane C5H6 FW 66.10 [6746‑94‑7]

HC

663018-5G

5 g

663018-25G

25 g

1,3-Di­ethynyl­ben­zene, 97%

 80 wt. % in xylene 530409-50G

50 g

530409-125G

125 g

Pro­pargyl chloride, 98% 3-Chloro-1-pro­pyn­e C3H3Cl FW 74.51 [624‑65‑7]

HC Cl

143995-5G

5 g

143995-25G

25 g

C10H6 FW 126.15 [1785‑61‑1]

CH

HC

632104-1G

1 g

632104-5G

5 g

1,4-Di­ethynyl­ben­zene, 96% C10H6 FW 126.15 [935‑14‑8]

HC

CH

632090-5G

5 g

3-Dimethyl­amino-1-pro­pyn­e, 97%

Pro­pargyl chloride solution 3-Chloro-1-pro­pyn­e C3H3Cl FW 74.51 [624‑65‑7]

HC Cl

 70 wt. % in toluene 384321-100ML

100 mL

4-(Tri­fluoro­methoxy) phenyl­acetyl­ene, 97% 4-Ethynyl-1-(tri­fluoro­methoxy) ben­zene C9H5F3O FW 186.13 [160542‑02‑9]

N,N-Dimethyl­pro­pargyl­amine; N,N-Dimethyl-2-pro­pyn­yl­amine C5H9N FW 83.13 [7223‑38‑3]

CH3 N

HC

CH3

143065-5G

5 g

143065-25G

25 g

1,1-Dimethyl-N-tert-octyl­pro­pargyl­amine, 96% F3CO

CH

C13H25N FW 195.34 [263254‑99‑5]

HC

H CH3 N

CH3 CH3 H3C CH3 CH3 CH3

513709-1G

672858-1G

1 g

1-[(Tri­methyl­silyl)ethynyl]-3-fluoro­ben­zene, 97% C11H13FSi FW 192.30 [40230‑96‑4]

N-tert-Amyl-1,1-dimethyl­pro­pargyl­amine, 98%

513695-5G

CH3 I

Miscellaneous Alkynes

514934-5G

563463-25ML

C11H13ISi FW 300.21 [134856‑58‑9]

5 mL 25 mL

Si CH3

563463-5ML

CH3

563439-25ML

CH3 CH3

CH3 Si CH3

563439-5ML

C10H19N FW 153.26 [2978‑40‑7]

(4-Fluoro­phenyl­ethynyl)tri­methyl­silane, 97% C11H13FSi FW 192.30 [130995‑12‑9]

[4-(Tri­fluoro­methyl)phenyl](tri­methyl­silyl)acetyl­ene F3C C12H13F3Si FW 242.31 [40230‑95‑3]

CH3 Si CH3 F

CH3

563269-5G

5 g

C8H7N FW 117.15 [52670‑38‑9]

1 g

597651-5G

5 g

3-Ethynyl­ani­line, ≥98%

1-(3’-Tri­fluoro­methyl­phenyl)-2-(tri­methyl­silyl)acetyl­ene C12H13F3Si FW 242.31 [40230‑93‑1] F3C

C8H7N FW 117.15 [54060‑30‑9]

Si CH3 CH3

562661-5ML

5 mL

562661-25ML

25 mL

CH NH2

597651-1G

1-[(Tri­methyl­silyl)ethynyl]-3-(tri­fluoro­methyl)ben­zene, 98% CH3

1 g

2-Ethynyl­ani­line, 98%

498289-5G

TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit sigma-aldrich.com/chemicalsynthesis.

CH H2N

5 g

19

4-Ethynyl­ani­line, 97%

2-Methyl-3-butyn-2-amine, 95%

1-Amino-4-ethynyl­ben­zene C8H7N FW 117.15 [14235‑81‑5]

3-Amino-3-methyl-1-butyne; 1,1-Dimethyl­pro­pargyl­amine C5H9N FW 83.13 [2978‑58‑7]

H2N

CH

481122-5G

5 g

C14H10 FW 178.23 [29079‑00‑3]

CH

5 g

1-Ethynyl­cyclo­hex­ene, 99% C8H10 FW 106.17 [931‑49‑7]

CH

NH2 CH3 CH3

5 g

N-Methyl­pro­pargyl­amine, 95% 3-Methyl­amino-1-pro­pyn­e C4H7N FW 69.11 [35161‑71‑8]

H N

HC

CH3

150223-1G

1 g

150223-5G

5 g

N-Methyl-N-pro­pargyl­benzyl­amine, 97%

316571-5G

5 g

316571-25G

25 g

1-Ethynyl­cyclo­hexyl­amine, 98% C8H13N FW 123.20 [30389‑18‑5]

NH2

CH

177024-1G

1 g

177024-5G

5 g

1-Ethynyl-3,5-dimethoxy­ben­zene C10H10O2 FW 162.19 [171290‑52‑1] 98% (CP)

H3CO

H3CO

1 g

588520-5G

5 g

4-Ethynyl-N,N-dimethyl­ani­line, 97% 4-Dimethyl­amino­phenyl­acetyl­ene; 1-Ethynyl-4-dimethyl­ani­line C10H11N FW 145.20 [17573‑94‑3]

H3C N H3C

CH

592609-1G

1 g

592609-5G

5 g

1-Ethynyl-2-nitro­ben­zene, 98% C8H5NO2 FW 147.13 [16433‑96‑8]

CH NO2

519456-5G

5 g

1-Ethynyl-4-nitro­ben­zene, 97% C8H5NO2 FW 147.13 [937‑31‑5]

O2N

CH

519294-1G

1 g

519294-5G

5 g

1-Ethynyl-4-phen­oxy­ben­zene, 97% HC

Pargyline C11H13N FW 159.23 [555‑57‑7]

O

1 g

521213-5G

5 g

CH

M74253-5G

5 g

M74253-25G

25 g

1,8-Nona­diyne, 98% C9H12 FW 120.19 [2396‑65‑8]

HC

CH

10 g

1,7-Octa­diyne, 98% C8H10 FW 106.17 [871‑84‑1]

CH

HC

161292-1G

1 g

161292-10G

10 g

Pro­pargyl­amine, 98% 3-Amino-1-pro­pyn­e; 2-Pro­pyn­yl­amine C3H5N FW 55.08 [2450‑71‑7]

HC NH2

P50900-1G

1 g

P50900-5G

5 g

P50900-25G

25 g

Pro­pargyl­amine hydrochloride, 95% 3-Amino-1-pro­pyn­e hydrochloride; 2-Pro­pyn­yl­amine hydrochloride C3H5N · HCl FW 91.54 [15430‑52‑1]

HC

• HCl NH2

P50919-1G

1 g

P50919-10G

10 g

Tri­pro­pargyl­amine, 98% C9H9N FW 131.17 [6921‑29‑5] T84964-5G

521213-1G

1,6-Hepta­diyne, 97% HC

N CH3

161306-10G CH

588520-1G

407437-1G

HC

CH

1 g

Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com.

HC

N

CH CH

5 g

Functionalized Alkynes

521175-5G

C7H8 FW 92.14 [2396‑63‑6]

8

687189-5G

4-Ethynyl­biphenyl, 97%

C14H10O FW 194.23 [4200‑06‑0]



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