Advances in the synthesis of α-quaternary α-ethynyl α-amino acids

Abstract

α-Quaternary α-ethynyl α-amino acids are an important class of non-proteinogenic amino acids that play an important role in the development of peptides and peptidomimetics as therapeutic agents and in the inhibition of enzyme activities. This review provides an overview of the literature concerning synthesis and applications of α-quaternary α-ethynyl α-amino acids covering the period from 1977 to 2015.

Asymmetric hydroalkylation of alkynes and allenes with imidazolidinone derivatives: α-alkenylation of α-amino acids

“…1 The introduction of a fourth substituent to the a-carbon (carbon bears the amino and carboxyl groups) of amino acids is a common approach in the asymmetric synthesis of quaternary a-AAs. 2 While enantioselective alkylation at a-carbon is well developed, the introduction of unsaturated substituents (aryl and alkenyl) at this carbon has proved more challenging. 3 Alkenyl a-AAs are important structure motifs to serve as building blocks in synthetic chemistry and drug discovery.…”

“…These structures have shown interesting biological activities such as antibiotic and anticancer properties. 4 Despite of its relevance, the methodologies for the synthesis of enantiopure alkenyl amino acids are limited, 5 among them [2,3]-sigmatropic rearrangement of selenimides, 6 a-2-tosylethenylation of (S)-2-(pyrrolidin-1-yl)propanoic acid esters, 7 and use of alkenylboronic acids are the most used. 8 Recently, an intramolecular method for the a-alkenylation of a-AA was reported using diastereoselective rearrangement of an N 0 -alkenyl urea substrate 9 according to the Seebach's "self-regeneration of stereocenters" method (Scheme 1a).…”

1‐Aminovinylphosphonate Esters as Substrates for the Diels‐Alder Reaction: First Synthetic and Theoretical Study

“…Among non‐proteinogenic amino acids, quaternary α‐amino acids constitute a family of compounds which find application in several research fields, from the development of new catalytic systems to the synthesis of pharmaceuticals . Within this context, α,β‐dehydroalanines are useful precursors of quaternary carbocyclic α‐amino acids through cycloaddition reactions (Figure )…”

C-Quaternary alkynyl glycinols via the Ritter reaction of cobalt complexed alkynyl glycols

“…1) are versatile building blocks for the construction of complex biologically active molecules. [1][2][3][4][5][6][7] While there is a good arsenal of methods for the synthesis of Cquaternary alkynyl glycines 2, 1,2 the direct access to C-quaternary alkynyl glycinols 1 is limited to few alternatives avoiding the reduction of carboxyl groups in glycines 2. The literature search revealed only the Seyferth-Gilbert homologation of a serinal derivative; 8 aminolysis of alkynyl epoxides 7,[9][10][11][12] and the insertion of a nitrene into a propargylic C-H bond 13 as synthetically useful approaches.…”