Synthesis of a bicyclic delta-amino acid as a constrained Gly-Asn dipeptide isostere.

Abstract:

:Delta-amino acids are very attractive in drug discovery, especially in the peptidomimetic area, because of their capability to act as dipeptide isosteres and reverse turn mimetics. Herein we report the synthesis of a rigid delta-amino acid constrained by a 3-aza-6,8-dioxabicyclo[3.2.1]octane-based scaffold, which can be considered as a Gly-Asn dipeptide mimetic. Key steps are the condensation of glycidol and tartaric acid derivatives, and the intramolecular trans-acetalization of the oxidized adduct to give the bicyclic delta-amino acid. Starting from L-tartaric acid derivative, it was achieved the corresponding Gly-D-Asn isostere, whereas from the enantiomeric D-tartaric acid derivative the corresponding Gly-L-Asn isostere could be obtained, thus giving access to both enantiomeric dipeptide sequences.

journal_name

Amino Acids

journal_title

Amino acids

authors

Trabocchi A,Menchi G,Danieli E,Guarna A

doi

10.1007/s00726-007-0636-7

subject

Has Abstract

pub_date

2008-06-01 00:00:00

pages

37-44

issue

1

eissn

0939-4451

issn

1438-2199

journal_volume

35

pub_type

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