Abstract
The first synthesis of the cyclic peptide natural product, argadin is reported. Use of a solid-phase approach featuring side-chain resin attachment through histidine and a novel protecting group strategy allows rapid and efficient access to the argadin backbone, whereupon the unusual 3-amino-5-hydroxy-2-pyrrolidone moiety of the peptide is introduced by oxidative cyclisation of a homoserine residue. Argadin is shown to exist as a 5:1 mixture of diastereoisomers at the 5-hydroxy centre of the pyrrolidone ring, and inhibits a representative family-18 chitinase (ChiBl from Aspergillus fumigatus) with K-i = 33 nm. The high-resolution X-ray crystal structure of synthetic argadin in complex with the same enzyme shows the binding of a single diastereoisomer as previously observed with the authentic natural product.
Original language | English |
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Pages (from-to) | 5002-5006 |
Number of pages | 5 |
Journal | European Journal of Organic Chemistry |
Volume | 22 |
DOIs | |
Publication status | Published - 2006 |