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The Frondosins: An Unusual Synthetic and Stereochemical Journey
Author(s) -
VanHeyst Michael D.,
Wright Dennis L.
Publication year - 2015
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201403116
Subject(s) - stereocenter , chemistry , stereochemistry , natural product , metathesis , enantiomer , enantioselective synthesis , total synthesis , combinatorial chemistry , organic chemistry , catalysis , polymer , polymerization
Isolated from the marine sponge Dysidea frondosa , the frondosin family of meroterpenoid natural products were shown to be antagonists of the binding of the cytokine interleukin‐8 to its receptor. With implications of interleukin‐8 management being associated with a wide range of acute and chronic inflammatory disorders, as well as tumor progression and/or metathesis, there have been a multitude of syntheses of these natural products in the hopes of developinging new pharmacological agents. However, assignment of the absolute configurations of these natural products became unclear, because the first two syntheses of frondosin B, by Danishefsky and by Trauner, produced conflicting assignments for the single stereogenic center at C8. Here we describe the initial stereochemical mystery surrounding the Danishefsky and Trauner syntheses and provide evidence through ensuing syntheses of frondosins B and A that resolve this issue. These subsequent asymmetric syntheses have established that (1) the natural product occurs as the R enantiomer, and (2) a late‐stage stereochemical inversion occurred during the Trauner and Wright syntheses of frondosin B.