Asymmetric synthesis of Fmoc-threo-HOAsn for the total synthesis of nicrophorusamide A†

Abstract

Fmoc-protected β-hydroxyasparagine is an essential structural motif in organic chemistry, widely present in natural products and clinically important drugs, such as antibiotics. Here, a diastereoselective synthesis of Fmoc-protected HOAsn from a simple Garner's aldehyde has been developed. The Fmoc protected Garner's aldehyde reacted with triphenylmethyl isocyanide and formic acid at 60 °C, affording good yield with excellent diastereoselectivity. The application of the Passerini reaction product Fmoc-protected HOAsn for Fmoc-SPPS towards the synthesis of nicrophorusamide A and its analogues has also been reported, which is conducive to systematic SAR studies.