Synthesis of the C42–C52 part of ciguatoxin CTX3C

Abstract 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 C 3 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.