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DOI: 10.1055/s-0036-1591836
The Structure Elucidation of Haprolid
Publication History
Received: 21 October 2017
Accepted: 26 October 2017
Publication Date:
24 November 2017 (online)
Dedicated to Professor Cesare Gennari on the occasion of his 65th birthday
Abstract
The assignment of two stereocenters of the natural product haprolid through the application of a profile hidden Markov model (HMM) and its confirmation through total synthesis of the natural product and of two of its diastereomers are reported. The structure elucidation of this polyketide-peptide hybrid natural product is a telling showcase of how difficult it can be to determine the absolute configuration of isolated stereocenters and the benefits of a gene cluster analysis for structure determination. The key steps of the synthesis are a selective epoxidation of a terminal olefin and the stereodivergent macrolactonization strategy. Furthermore, the biological evaluation of all products showed that all diastereomers are potent inhibitors of hepatocellular carcinoma cell lines.
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For the use of terpenes in polyketide synthesis, see: