Stereoselective Access to Azetidine-Based α-Amino Acids and Applications to Small Peptide Synthesis

Abstract

Non-natural azetidine-based amino acids (Aze) present interesting features in protein engineering. A simple organometallic route toward unsaturated carboxylic acid precursors is presented. Subsequent metal-catalyzed asymmetric reduction allowed for the synthesis of a new library of 2-azetidinylcarboxylic acids, which were finally employed in the formation of small peptide chains.

Uncommon Four‐Membered Building Blocks – Cyclobutenes, Azetines and Thietes

“…Most of these compounds proved to be stable and allowed for establishing a new library of functionalized building blocks (Scheme 30). [80] Further asymmetric syn ‐reduction of the double bond employing a ruthenium complex in the presence of a BINAP‐type ligand led to the desired aze derivatives 48 in good yields and reasonable enantiomeric ratios (up to 94 : 6).…”

TiCl4‐Mediated [2+2] Cycloaddition for Synthesis of Isolable CF3‐Substituted 2‐Azetines

“…[7] The molecular structure of 2-azetines, on the other hand, has been discussed based on limited examples: Barluenga et al reported the structure of azetinylcarbene compound I, [8] and Didier and co-workers succeeded in the isolation and characterization of II as a unique cyclic amino acid (Figure 1b). [9] Synthetic studies of 2-azetines have encompassed investigations into intermolecular [2 + 2] cycloaddition processes. Kobayashi and co-workers reported [2 + 2] cycloaddition reactions of imines and alkynyl sulfides in the presence of lanthanide triflate [Ln(OTf) 3 ] or BF 3 •OEt 2 catalyst (Scheme 1, Eq.…”

Strain-release arylations for the bis-functionalization of azetidines

“…6 In addition, we recently contributed to this field through manipulation of unsaturated analogs – 2 H -azetines – via Diels–Alder cycloadditions or hydrogenation reactions. 7…”