Efficient, highly stereoselective approaches have been developed to (+)-actinobolin (1) and (-)-bactobolin (3) from bridged α-keto lactone 11, which can be readily prepared via intramolecular SnCl4 catalyzed ene reaction of cyclohexenol glyoxylate (5). A novel method has been developed for direct, stereoselective reductive sulfonamidation of 11 to simultaneously introduce a protected C-4 amino group of the natural products and generate the C-4/4a relative stereochemistry. It was found that a PMS ((p-methylbenzyl)sulfonyl) nitrogen protecting group was useful in the actinobolin synthesis, but for bactobolin the SES ((β-(trimethylsilyl)ethyl)sulfonyl) group was necessary. The C-3 substitution and stereochemistry of the antibiotics was established by manipulation of the carbonyl group of the bridged lactone intermediates, and in particular, a novel organocerium reagent was applied to this part of the bactobolin synthesis (cf. 35 → 37). In both syntheses an unprecedented intramolecular enolate C-acylation was used to prepare the bicyclic enol lactone systems.
All Science Journal Classification (ASJC) codes
- Colloid and Surface Chemistry