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Synlett 2002(9): 1388-1404
DOI: 10.1055/s-2002-33552
ACCOUNT
© Georg Thieme Verlag Stuttgart · New York

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

Carmen Nájera*
Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Alicante, Apdo. 99, 03080 Alicante, Spain
Fax: +34(965)903549; e-Mail: cnajera@ua.es;
Further Information

Publication History

Received 10 October 2001
Publication Date:
17 September 2002 (online)

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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

Key words

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

17

Chinchilla, R. unpublished results.

25

Guillena, G. private communication.

38

Polystyrene crosslinked with 1% divinylbenzene 200-400 mesh 17 mmol/g.

54

PM3 calculations (Hyperchem 50 from Hypercube Inc.) gave the following frontier obital energies for oxazinone 51: EHOMO = -946eV ELUMO = 094eV [46c] and for pyrazinone 52: EHOMO = -941eV ELUMO = -108 eV. [47b]

63

MOPAC: CS Chem3D 45, CambridgeSoft Corporation.

73

Soriano, J. M. manuscript in preparation.