Synlett
DOI: 10.1055/s-0036-1588515
letter
© Georg Thieme Verlag Stuttgart · New York

Chemoenzymatic Formal Total Synthesis of Pancratistatin from Narciclasine-Type Compounds via Myers Transposition: Model Study for a Short Conversion of Narciclasine to Pancratistatin

Ringaile Lapinskaite, Mukund Ghavre, Chelsea L. Rintelmann, Korey Bedard, Helen E. Dela Paz, Tomas Hudlicky*
  • Department of Chemistry and Centre for Biotechnology, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, ON L2S 3A1, Canada   Email: thudlicky@brocku.ca
The authors are grateful to the following agencies for financial support of this work: Natural Sciences and Engineering Research Council of Canada (NSERC) (Idea to Innovation and Discovery Grants), Canada Research Chair Program, Canada Foundation for Innovation (CFI), TDC Research, Inc., TDC Research Foundation, the Ontario Partnership for Innovation and Commercialization (OPIC), and The Advanced Biomanufacturing Centre (Brock University).
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Publication History

Received: 06 June 2017

Accepted after revision: 30 June 2017

Publication Date:
03 August 2017 (eFirst)

Dedicated to Professor Victor Snieckus on the occasion of his 80th birthday and in recognition of his many contributions to the art of organic synthesis

Abstract

A formal total synthesis of pancratistatin was accomplished by conversion of advanced intermediates, used in the synthesis of narciclasine, to pancratistatin precursors via Myers’ reductive transposition as the key strategic step. The synthesis began with the whole cell fermentation of m-dibromobenzene with JM109(pDTG601a), a recombinant strain that over-expresses toluene dioxygenase, which provided the corresponding cis-dihydrodiol 16 as a single isomer with complete optical purity. The key reductive transposition of the allylic alcohol 8a to olefin 9a allowed for further installation of the C-1/C-2 trans-diol, ­required for the pancratistatin scaffold, through the introduction of a cyclic sulfate and its subsequent opening. The formal synthesis of pancratistatin was accomplished in 14 steps (12 operations) from commercially available m-dibromobenzene. Experimental and spectral data are provided for all new compounds.

Supporting Information