Patent ID: 7939679
Filing Date: 2011-05-10
Classification: C07D,C07F

Abstract:
1. A method for preparation of CTX1B including the following steps: oxidizing the double bond of compound A by osmium tetra oxide to form a diol derivative of compound A, and transforming the diol to aldehyde by oxidative cleavage using sodium periodate, then reducing the aldehyde to alcohol using sodium borohydride and obtaining compound 1; transforming the alcohol of compound 1 to compound 2 using diphenyldisulfide•tributylphosphine; transforming said compound 2 using α-chlorosulphide to synthesize compound B; joining under presence of DTBMP said compound B to ABCDE ring segments of compound C as O,S-acetal using silver triflate and forming compound 3; removing TIPS group of said compound 3 using TBAF and forming compound 4; joining pentafluorophenylpropiolate to alcohol of said compound 4 using trimethylphosphine and forming compound 5; carrying out radical cyclization reaction on said compound 5 by treating with AIBN and tintributyl hydride and forming G ring part, so that said compound 5 transforms to carboxylic acid of compound D; transforming to methyl ester by acting trimethylsilyldiazomethane and forming compound 6; forming compound 7 by reducing methyl ester of said compound 6 by diisobutylaluminum hydrate under lower temperature condition, then transforming to olefin by Wittig reaction; forming compound 8 by forming F ring part by carrying out ring closure methathesis reaction using a Grubbs catalyst to said compound 7; synthesizing 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; and carrying out acid treatment on said compound E and obtaining CTX1B, wherein, in compounds A, B, C, D, E, CTX1B and compounds 1-8, NAP is 2-naphthylmethyl group, Me is methyl group, TIPS is triisopropylsilyl group, Ph is phenyl group, wherein DTBMP is 2,6-di-t-butyl-4-methylpyridine, TBAF is tetrabutylammonium fluoride, AIBN is α, α′-azobis(isobutyronitrile), and DDQ is 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.