From α-Amino Acids to Peptides: All You Need for the Journey

Abstract

In this account several tools necessary for the synthesis of peptides from α-amino acids are considered. Different strategies for the asymmetric synthesis of α-amino acids are studied. New chiral glycine and alanine imines as acyclic and cyclic templates for the asymmetric synthesis of different types of mono as well as dialkylated α-amino acids with acyclic and heterocyclic structures are reviewed. Their diastereoselective alkylation and final hydrolysis takes place under very mild reaction conditions. New polymer-supported cinchonidine and cinchonine ammonium salts and chiral binaphthol-derived aminoalkoxides (BINOLAMs), have been developed as catalysts for the asymmetric PTC alkylation of imino esters. The use of chiral oxazinone and pyrazinone α,β-didehydroamino acid derivatives in hydrogenation, Heck-arylation, cyclopropanation and Diels-Alder cycloaddition reactions for the asymmetric synthesis of α-amino acids are also studied. Azomethine ylides derived from saturated oxazinones can also be used in the asymmetric synthesis of prolines by means of diastereoselective dipolar cycloadditions. For the protection of α-amino acids new efficient reagents, Fmoc-P-OSu and Cbz-P-OSu, derived from poly(styrene-co-N-hydroxymaleimide) named as polymeric N-hydroxysuccinimide (P-HOSu), have been developed. Several new systems such as polymer-supported P-HOSu/DCC and polystyrene-bound P-TBTU or P-HBTU, together with non- polymeric thiouronium salts derived from 2-mercaptopyridine-1-oxide and TMU, such as HOTT and TOTT, and from DMPU, such as HODT and TODT, have been used as peptide coupling reagents, in solution and solid phase peptide synthesis, as well as for the preparation of primary amides, Weinreb amides and other hydroxamates, directly from carboxylic acids.

1 Introduction

2 Asymmetric Synthesis of α-Amino Acids

2.1 Electrophilic Alkylation of Chiral Glycine and Alanine
Templates

2.2 Electrophilic Alkylation with Chiral Phase-transfer
Catalysts

2.3 Chiral α,β-Didehydroamino Acid Derivatives

2.4 Chiral Azomethine Ylides

3 Protecting-group Reagents

4 Peptide Coupling Reagents

5 Conclusion

amino acids - phase-transfer catalysis - asymmetric catalysis - protecting groups - peptides

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