Method for synthesis of ciguatoxin ctx1b and compounds useful for the synthesis of ciguatoxin ctx1b

A method for preparation of CTX1B including following 10 processes,

• a double bond of compound A
• is oxidized by osmium tetra oxide and changed to diol derivative of compound A, transformed the diol to aldehyde by oxidation cleavage by sodium periodate, then reduced the aldehyde to alcohol using sodium borohydride and obtain compound 1 (process 1),
• alcohol of compound 1 is transformed to compound 2 using diphenyldisulfide•tributylphosphine (process 2),
• said compound 2 is transformed to α-chrolosulphide and synthesize compound B,
• under the presence of DTBMP said compound B is joined to the ABCDE ring segments compound C as O,S-acetal using silver triflate and compound 3 is formed (process 3),
• TIPS group of said compound 4 is removed using TBAS and form compound 4 (process 4),
• pentafluorophenylpropiolate is joined to alcohol of said compound 4 using trimethylphosphine and compound 5 is formed (process 5),
• carry out radical cyclizing reaction on said compound 5 by treating with AIBN and tintributyl hydride and form G ring part, so that compound 5 transforms to carboxylic acid compound D, then
• transforms to methyl ester by acting trimethylsilyldiazomethane and forms compound 6 (process 6),
• forms compound 7 (process 7) by reducing methyl ester of said compound 6 by diisobutylaluminum hydrate under lower temperature condition, then transforms to olefin by Wittig reaction,
• forms compound 8 (process 8) by forming F ring part by carrying out ring closure methathesis reaction acting Grubbs catalyst to said compound 7,
• synthesizes compound E, 1,2-diol of A ring side chain of which is protected by naphthylacetal, by oxidizing 6 NAP groups using DDQ and removing 5 NAP groups (process 9), then
• carries out acid treatment on said compound E (process 10),
• wherein, in compounds A, B, D, E, CTX1B and compounds 1-8, NAP is 2-naphthylmethyl group, Me is methyl group, TIPS is triisopropylsilyl group, Ph is phenyl group, further, shortened mark DTBMP is 2,6-di-butyl-4-methylpyridine, TBAF is tetrabutylammonium fluoride, AIBN is α,α′-azobis(isobutyronitrile), DDQ is 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.