Synlett 2021; 32(17): 1747-1750
DOI: 10.1055/s-0040-1719824
letter

Diastereoselective Synthesis of (3R,5R)-γ-Hydroxypiperazic Acid

Taylor A. Gerrein
,
Yassin M. Elbatrawi
,
This work was supported by a grant from the National Science Foundation (Grant No. CHE2109008).


Abstract

We report an asymmetric synthesis of the (3R,5R)-γ-hydroxypiperazic acid (γ-OHPiz) residue encountered in several bioactive nonribosomal peptides. Our strategy relies on a diastereoselective enolate hydroxylation reaction and electrophilic N-amination to provide the acyclic γ-OHPiz precursor. This orthogonally protected α-hydrazino acid intermediate is amenable to late-stage diazinane ring formation following incorporation into a peptide chain. We determined the N-terminal amide rotamer propensity of the γ-OHPiz residue and showed that the γ-OH substituent enhances trans-amide bias relative to piperazic acid.

Supporting Information



Publication History

Received: 24 June 2021

Accepted after revision: 19 July 2021

Article published online:
12 August 2021

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