Open AccessConvergent Synthesis of the C1–C29 Framework of Amphidinolide F
Author(s) -
Filippo Romiti,
Ludovic Decultot,
J. Stephen Clark
Publication year - 2022
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.2c00850
Subject(s) - chemistry , oxonium ion , aldol reaction , carbenoid , intramolecular force , stereochemistry , tetrahydrofuran , convergent synthesis , aldehyde , stereoselectivity , total synthesis , nucleophile , epoxide , rhodium , organic chemistry , catalysis , ion , solvent
The complete carbon framework of the macrocyclic marine natural product amphidinolide F has been prepared by a convergent synthetic route in which three fragments of similar size and complexity have been coupled. Key features of the syntheses of the fragments include the stereoselective construction of the tetrahydrofuran in the C1-C9 fragment by oxonium ylide (free or metal-bound) formation and rearrangement triggered by the direct generation of a rhodium carbenoid from 1-sulfonyl-1,2,3-triazole, the highly diastereoselective aldol reaction between a boron enolate and an aldehyde with 1,4-control to prepare the C10-C17 fragment, and the formation of the tetrahydrofuran in the C18-C29 fragment by intramolecular nucleophilic ring opening of an epoxide with a hydroxyl group under acidic conditions.