From?-lactams to?- and?-amino acid derived peptides

Abstract

The potential of beta-lactams as intermediates for the access to alpha- and beta-amino acid-derived peptides is shortly reviewed, with major focus on the technologies developed in our group. The two general strategies lie, on one side, in the oxidative ring expansion of 3-hydroxy beta-lactams to N-carboxy alpha-amino acid anhydrides or Leuch's anhydrides and subsequent coupling with alpha-amino acid esters and, on the other side, in the nucleophilic ring opening of N-Boc-beta-lactams. Both approaches have been successfully applied to the synthesis of alpha,beta-diamino acid, alpha-amino-beta-hydroxy acid, polyhydroxylated alpha-amino acid, alpha,alpha-disubstituted alpha-amino acid, beta-amino acid, beta-amino-alpha-hydroxy acid and beta,beta-disubstituted beta-amino acid derived peptides. Because of the mild reaction conditions needed for the above transformations and the highly stereoselective procedures employed for the construction of the starting beta-lactam ring, the whole process allows the production of optically pure final products.

Cloning and Characterization of a Novel β-Transaminase fromMesorhizobiumsp. Strain LUK: a New Biocatalyst for the Synthesis of Enantiomerically Pure β-Amino Acids

“…The higher stability of ␤-amino acid peptides against peptidases also has drawn great interest in peptide chemistry (16). The significance of ␤-amino acids and their related molecules attracts increasing attention for the synthesis of ␤-amino acids (5,37,38,41), especially for the enantioselective synthesis of ␤-amino acids (26,28,30,40). Although recent reviews of the biocatalytic synthesis of ␤-amino acids elaborated a wide range of approaches, most of the methods dealt with the chiral resolution of precursors using hydrolytic enzymes (29).…”

Divergent, stereoselective access to heterocyclic α,α-quaternary- and β2,3,3-amino acid derivatives from a N-Pmp-protected Orn-derived β-lactam

“…The intermolecular nucleophilic ring opening of N-Boc-β-lactams has also been successfully applied to the synthesis of β-amino acids, β-amino-α-hydroxy acid and β,β-disubstituted-β-amino acid derived peptides. 38,39 Based on these precedents, we envisaged a route for the preparation of conformationally restricted 2-piperidinone-containing β-amino acid derivatives, using again β-lactam 7 as the key precursor. Thus, removal of the Z protecting group from 7 by catalytic hydrogenation promoted the formation of the 3.5-spiro derivative 11 in good yield (84%), through a 6-exo-trig ring closure (Scheme 3).…”

Advances in the chemistry of ?-lactam and its medicinal applications

“…5–13 In addition, the β-lactam scaffold has found new pharmaceutical applications other than its use as antibiotics, such as LHRH antagonists, 14 cholesterol-absorption inhibitors, 15 and anticancer agents. 16–19 The ring strain of the β-lactam skeleton facilitates ring-opening reactions, 8,20,21,22 and this unique property has been exploited for the synthesis of a variety of medicinally active compounds.…”