Synthesis of the C42–C52 part of ciguatoxin CTX3C

The C42–C52 part of ciguatoxin CTX3C (1) was synthesized from tri-O-acetyl d-glucal. The synthetic segment had a tetrahydropyran ring corresponding to the ‘C49-reduced’ L-ring of 1, designed to avoid side reactions due to acid-labile C49 acetal carbon during acidic reductive conditions planned in further synthesis toward 1. The vicinal dimethyl part at C47–C48 was constructed by a stepwise conjugate addition/methylation procedure. The C50–C52 unit was installed by Grignard addition of the C3 unit followed by spirocyclization and reductive cleavage of the spirocyclic acetal. Stereoselective assembly of the C42–C44 part was achieved by Brown’s asymmetric crotylboration.

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