A Fast Procedure for the Preparation of Amides/Peptides from Carboxylic Acids and Azides via Two Redox Reactions: Application to the Synthesis of Methionine Enkephalin

Abstract

A one-pot self regulated approach for the synthesis of amides/peptides based on two reduction–oxidation (redox) reactions has been described. The primary and secondary amides/peptides are made by using azidotrimethylsilane and alkyl azides/α-azido acid derivatives respectively as the direct source of amine components. Benzeneselenol, generated in the reaction medium during carboxyl activation, has been found to be an effective reducing agent for the conversion of azides to primary amines. The methodology has been applied to the synthesis of methionine enkephalin.

Intramolecular C−H Amination Reactions: Exploitation of the Rh2(II)-Catalyzed Decomposition of Azidoacrylates

“…Purification by flash chromatography (1:99 EtOAc:hexanes) afforded the product s4 as a pale yellow low melting solid (0.622 g, 41%). The spectral data matched that reported by Ghosh and co-workers: 5 1 H NMR (CDCl 3 , 500 MHz) δ 7.83 (d, J = 8.0 Hz, 2H), 7.41 -7.33 (m, 3H), 6.93 (s, 1H), 3.90 (s, 3H); 13 Vinyl azide (s5). 4 The general procedure was followed using 0.405 g of sodium methoxide (7.5 mmol), 3.30 mL of methanol, 0.917 g of 4-chlorobenzaldehyde (6.52 mmol), and 3.00 g of methyl azidoacetate (26.10 mmol).…”

“…Purification by flash chromatography (2:98 EtOAc:hexanes) and then recrystallization from hexanes afforded the product as a yellow solid (0.675 g, 29%): 1 H NMR (CDCl 3 , 500 MHz) δ 7.77 (d, J = 8.0 Hz, 2H), 7.42 (d, J = 8.5 Hz, 2H), 6.93 (s, 1H), 3.91 (s, 3H), 1.34 (s, 9H); 13 Vinyl azide (s4). 5 The general procedure was followed using 0.601 g of sodium methoxide (11.1 mmol), 4.0 mL of methanol, 0.750 mL of benzaldehyde (7.4 mmol), and 2.53 g of methyl azidoacetate (22.3 mmol). Purification by flash chromatography (1:99 EtOAc:hexanes) afforded the product s4 as a pale yellow low melting solid (0.622 g, 41%).…”

Natural Occurrence, Syntheses, and Applications of Cyclopropyl-Group-Containing α-Amino Acids. 1. 1-Aminocyclopropanecarboxylic Acid and Other 2,3-Methanoamino Acids

“…178 Additionally, the ACC-containing dipeptides 107 have been synthesized from 1-azidocyclopropanecarboxylic acid and glycine by a self-regulating redox process using diphenyl diselenide (Figure 3). 179,180 The conformational preferences of 1-aminocyclopropanecarboxylic acid homopeptides have been studied extensively by computations, 181,182 IR and NMR spectroscopy, 181 as well as X-ray diffraction. 183 Peptides incorporating one ACC unit have been explored by ab initio and semiempirical computational methods 184,185 as well as experimentally by X-ray structure analyses.…”

Catalytic Staudinger—Vilarrasa Reaction for the Direct Ligation of Carboxylic Acids and Azides

“…Later, Vilarrasa et al examined and optimized the reactions of Staudinger phosphazenes with carboxyl derivatives (cyclic anhydrides, mixed anhydrides, thioesters, among others) and applied their findings to the synthesis of peptides and macrolactam-like natural products. The reactions with other carboxyl and carbonate derivatives (RCOCl, simple esters intramolecularly, , CH 3 COOCHO, Boc 2 O, selenoesters, and activated esters) have several “fathers” apart from our own research group. While some researchers name the general process RCO-LG + R 3 P + N 3 R the Staudinger−Vilarrasa reaction (henceforward, S−V reaction or S−V peptide ligation), other authors refer to these reactions as particular cases of “aza-Wittig” processes. − …”