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A New Approach to Models of the 4,5‐Dihydroxycyclopentenone Core of the Kodaistatins A–D: Elucidation of the Diol Configuration in Kodaistatin A
Author(s) -
Peter David,
Brückner Reinhard
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201701185
Subject(s) - aldol reaction , cyclopentenone , stereocenter , intramolecular force , chemistry , diol , moiety , ketene , stereochemistry , silylation , acetal , michael reaction , enantioselective synthesis , organic chemistry , catalysis
The kodaistatins A–D are strongly anti ‐diabetic natural products from Aspergillus terreus that hold some promise of a novel diabetes cure. However, considerations of that kind face two drawbacks: 1) The kodaistatins A–D contain a heavily substituted pulvinone/cyclopentenone combination; 2) they are 1,2‐diols, the 3D structures of which have not been assigned yet. However, we can exclude two of the four possible stereostructures. We conclude that kodaistatin A is a trans ‐, not a cis ‐diol from NMR comparisons with a pair of cis , trans ‐isomeric kodaistatin models, which we synthesized in 11 and 12 steps, respectively. The stereocenters of the diol moiety arose from stereocomplementary, highly diastereoselective aldol additions of a lithium enolate or the corresponding silyl ketene acetal. The cyclopentenone moieties stemmed from intramolecular aldol additions and ensuing dehydrations. The requisite enolates were obtained by the reduction of α‐bromoketones with samarium diiodide.