Synthesis and Absolute Configuration of Demethyl (C‐11) Cezomycin

Abstract

The synthesis of (-)-demethyl (C-11) cezomycin was achieved through an efficient route that features the use of a Kulinkovich reaction to couple two multifunctionality-containing fragments and a cascade of ring opening of cyclopropanol/1,5-hydrogen shift/desilylation-oxidation. The hidden yet undeniable problem of irreproducible specific rotation for this family of compounds was solved by sufficient acidification. The absolute configuration for the natural product was thus established as the mirror image of the synthetic sample.

Chemical Syntheses and Chemical Biology of Carboxyl Polyether Ionophores: Recent Highlights

“…We have tried to extract the strategic disconnections toward the carbon skeletons and key methods involved in the construction of the structural subunits, rather than comprehensively detailing every synthetic step from all the different approaches. A compilation of synthetic studies on other carboxyl polyether ionophore natural products completed in the time period from 2001 to 2018 is given in Table S1 (Supporting Information) with key transformations highlighted …”

Metallacycle-mediated cross-coupling in natural product synthesis

“…214 Here, intermolecular Kulinkovich reaction between ester 180 and terminal alkene 181 was employed to generate hydroxycylopropane product 182 that, in subsequent steps, was cleaved by the action of Fe(NO 3 ) 3 and advanced to the central spiroketal motif of the target (Figure 69B). …”

A Novel Allyl Transfer Coupled with a Grob Fragmentation

“…During our total synthesis of demethyl (C‐11) cezomycin, the most recent member in the pyrrol ether family of antibiotics, it was desired to remove the TBS protecting group in the intermediate 1 a to release a free OH group at the C‐6 position (Figure ). As the functionalities in this simple compound are not particularly unstable according to the existing knowledge, the desilylation was expected to be smooth and clean.…”