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Synlett 2021; 32(17): 1747-1750
DOI: 10.1055/s-0040-1719824
DOI: 10.1055/s-0040-1719824
letter
Diastereoselective Synthesis of (3R,5R)-γ-Hydroxypiperazic Acid
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.
Key words
nonribosomal peptides - natural products - piperazic acid - α-hydrazino acid - oxaziridineSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1719824.
- Supporting Information
Publication History
Received: 24 June 2021
Accepted after revision: 19 July 2021
Article published online:
12 August 2021
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