Dihydroxy olefin cyclizations

Scheme 43 Dihydroxy olefin cyclizations by Cheng and Stark [45]...

Ketone 1 is highly general and enantioselective for the epoxidation of fran.v-substituted and trisub-stituted olefins. Its ready availability and predictability potentially make this ketone useful. Its utilization in synthesis has been reported by other researchers.79 100 For example, Corey and coworkers have reported that pentaoxacyclic compound 24 can be obtained in 31% overall yield by enantioselective epoxidation of (f )-2,3-dihydroxy-2,3-dihydrosqualene (22) and subsequent cyclization of pentaepoxide 23 (Scheme 10.7).82 Eli Lilly has also used the epoxidation to introduce the epoxide on the sidechain of Cryptophycin 52 (Scheme 10.8).90 The epoxidation has been carried out at multi-kilogram scale at DSM-Catalytica. Around 100 kg of lactone 29 was prepared by the epoxidation of olefin 27 and subsequent in situ cyclization of epoxide 28 (Scheme 10.9).101... 

Lipstatin (58), comprised of a 3,5-dihydroxy-2-hexyl hexadeca-7,9-dienoic acid with cyclization of the hydroxy group at C-3 with the carboxylic acid to form a P-lactone and esterification of the hydroxy group at C-5 with a A-formyl leucine, was isolated from Streptomyces toxytricini. It inhibits gastric and pancreatic lipase and blocks intestinal absorption of lipids (40, 41). Reduction of the olefins led to the synthesis of tetrahydrolipstatin, which was approved in 1999 as Xenical (59) for the treatment of obesity (42-44). 

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