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Functionally substituted vinyl carbanions, 42. Synthesis of the top half of chlorothricolide
Author(s) -
Hirsenkorn Rolf,
Schmidt Richard R.
Publication year - 1990
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.1990199001165
Subject(s) - chemistry , hydroxylation , electrophile , carbanion , stereochemistry , moiety , bromide , cis–trans isomerism , nucleophile , cycloaddition , combinatorial chemistry , organic chemistry , catalysis , enzyme
β‐Lithiated functionally substituted acrylates 2a – c prove to be versatile building blocks for spirotetronate syntheses useful in top half syntheses of the aglycon chlorothricolide 1 of the macrolide antibiotic chlorothricin. The electrophilic‐nucleophilic cyclohexanone derivatives 27 ‐ cis / trans (with relative cis or trans relationship of the carboxylate group) required in this synthesis design are obtained via a cycloaddition route from pentenone in five steps. Generation of the dilithiated species from the acrylates 2a – c affords then the corresponding spirotetronates 32a – c , which serve as versatile intermediates in top half syntheses for different strategies in chlorothricolide total syntheses. Hydroxylation in the vinylic α‐position of the tetronate moiety and selective phenylselenylation provide the spirotetronates 39a ‐ cis / trans and 41a , which meet the requirements of a top half molecule. The same is true for a different strategy, which provides the aldehydes 42b ‐ cis / trans . The latter are then converted into the fully functionalized spirotetronates 44b ‐ cis / trans by treatment with vinylmagnesium bromide and subsequent hydroxylation at the vinylic α‐position. The investigations delineate similar convenient strategies for the syntheses of kijanolide and te‐tronolide, which are the aglycon portions of the structurally related macrolide antibiotics kijanimicin and tetrocarcin, respectively.