From prebiotic macromolecules to synthetic polypeptides: a new, efficient synthesis of α‐amino acid N‐carboxyanhydrides (NCAs)

Abstract

While polypeptide materials present important application potentialities, the expense of amino acid N‐carboxyanhydride (NCA) monomers strongly limits their applications. We present here a new, promising synthetic route to NCA through N‐carbamoylamino acid nitrosation by gaseous NOx(1 < x < 2) in the solid–gas phase. This very efficient reaction (which was originally developed in a prebiotic context) works in the absence of solvent and with minimum waste, and presents interesting economic features. Some mechanistic investigations aimed at the optimisation and scale‐up of this reaction in the solid‐gas phase are presented. © 2002 Society of Chemical Industry

Primary Amine and Solvent‐Induced Polymerizations of L‐ or D,L‐Phenylalanine N‐Carboxyanhydride

“…Therefore, the influence of the reaction conditions on the extent of cyclization was studied in more detail. Since cyclic oligo-and polypeptides are synthesized by numerous living organisms the present study is also of interest in connection with the work of Commeyras and coworkers [9][10][11][12] suggesting that a-amino acid NCA played an important role for the formation of oligo-and polypeptides in the prebiotic evolution.…”

Mechanistic Study of α‐Amino Acid N‐Carboxyanhydride (NCA) Polymerization by Capillary Electrophoresis

“…[37][38][39] Synthesis of N e -trifluoroacetyl-L-lysine Hexylamide (oligomer of DP n 5 1) DMF was distilled on 4 Å molecular sieves under vacuum and hexylamine was distilled from KOH under N 2 before the reaction. In a Schlenk flask fitted with a stir bar and a silicon septum, 0.5 g of Lys NCA was dissolved under N 2 at room temperature in 93.5 mL of freshly distilled DMF and then slowly added under N 2 via a transfer needle to another Schlenk flask fitted with a stir bar and a silicon septum containing 1.884 g of freshly distilled hexylamine dissolved in 9.5 mL of freshly distilled DMF.…”

Living Polymerization of α‐Amino Acid N‐Carboxyanhydrides (NCA) upon Decreasing the Reaction Temperature

“…After the synthesis of N a -carbamoyl-N e -trifluoroacetyl-L-lysine (Lys NCAA) by reaction between N e -trifluoroacetyl-L-lysine and potassium cyanate in aqueous medium, [33] Lys NCA was prepared by nitrosation of Lys NCAA using an NO/O 2 gas mixture. [34,35] In a Schlenk flask fitted with a stir bar and a silicon septum, 2.144 g of Lys NCA was dissolved under nitrogen in 50 mL of distilled DMF. Then, a volume of n-hexylamine corresponding to the desired molar ratio of monomer to initiator (M/I) was added and the reaction mixture was stirred at room temperature.…”