Biocatalytic synthesis of pikromycin, methymycin, neomethymycin, novamethymycin, and ketomethymycin

  • J Am Chem Soc. 2013 Jul 31;135(30):11232-8. doi: 10.1021/ja404134f.
Douglas A Hansen  1 ,  Christopher M Rath ,  Eli B Eisman ,  Alison R H Narayan ,  Jeffrey D Kittendorf ,  Jonathan D Mortison ,  Yeo Joon Yoon ,  David H Sherman
Affiliations
  • 1. Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
PMID: 23866020 DOI: 10.1021/ja404134f
Abstract

A biocatalytic platform that employs the final two monomodular type I polyketide synthases of the pikromycin pathway in vitro followed by direct appendage of D-desosamine and final C-H oxidation(s) in vivo was developed and applied toward the synthesis of a suite of 12- and 14-membered ring Macrolide natural products. This methodology delivered both compound classes in 13 steps (longest linear sequence) from commercially available (R)-Roche ester in >10% overall yields.

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