【药物名称】
化学结构式(Chemical Structure):
参考文献No.41795
标题:Synthetic methods for polyphenols
作者:Lippman, M.E.; Kozikowski, A.P.; Tueckmantel, W.; Romanczyk, L.J. Jr. (Mars, Inc.)
来源:WO 9919319
合成路线图解说明:

The oxidation of 5,7-bis(benzyloxy)-2(R)-[3,4-bis(benzyloxyphenyl]-3,4-dihydro-2H-1-benzopyran-3(S)-ol with Dess Martin periodinane (DMP) in dichloromethane gives the corresponding ketone (II), which is reduced with L-Selectride in THF yielding the 5,7-bis(benzyloxy)-2(R)-[3,4-bis(benzyloxyphenyl]-3,4-dihydro-2H-1-benzopyran-3(R)-ol (III). The oxidation of (III) with DDQ in presence of ethylene glycol affords the 2-hydroxyethoxy derivative (IV), which is condensed with (III) by means of titanium tetrachloride in THF/dichloromethane yielding the dihydroxylated dimer (V). The esterification of both hydroxyls of (V) with 3,4,5-tris(benzyloxy)benzoyl chloride (VI) by means of DMAP in pyridine affords the fully protected target compound (VII), which is finally debenzylated by hydrogenolysis with H2 over Pd/C in methanol/water.

合成路线图解说明:

Protection of (+)-catechin (I) with benzyl bromide gives the tetra-O-benzylcatechin (II). Epimerization of (II) in then accomplished by oxidation to ketone (III), using the Dess-Martin periodinane reagent, followed by ketone reduction with L-selectride to furnish the tetra-O-benzyl epicatechin (IV). Oxidation of (IV) with DDQ in the presence of ethyleneglycol gives rise to the 4-(hydroxyethoxy) derivative (V). Subsequent coupling between tetra-O-benzyl epicatechin (IV) and the 4-(hydroxyethoxy) derivative (V) in the presence of TiCl4 produces a mixture of epicatechin oligomers, from which the desired benzyl-protected dimeric compound (VI) is isolated by column chromatography. Finally, deprotection of the octa-benzyl ether (VI) is effected by hydrogenolysis in the presence of Pd/C.

参考文献No.561377
标题:Studies in polyphenol chemistry and bioactivity. 1. Preparation of building blocks from (+)-catechin. Procyanidin formation. Synthesis of the cancer cell growth inhibitor, 3-O-galloyl-(2R,3R)-epicatechin-4beta,8-[3-O-galloyl-(2R,3R)-epicatechin]
作者:T點kmantel, W.; et al.
来源:J Am Chem Soc 1999,121(51),12073
合成路线图解说明:

The oxidation of 5,7-bis(benzyloxy)-2(R)-[3,4-bis(benzyloxyphenyl]-3,4-dihydro-2H-1-benzopyran-3(S)-ol with Dess Martin periodinane (DMP) in dichloromethane gives the corresponding ketone (II), which is reduced with L-Selectride in THF yielding the 5,7-bis(benzyloxy)-2(R)-[3,4-bis(benzyloxyphenyl]-3,4-dihydro-2H-1-benzopyran-3(R)-ol (III). The oxidation of (III) with DDQ in presence of ethylene glycol affords the 2-hydroxyethoxy derivative (IV), which is condensed with (III) by means of titanium tetrachloride in THF/dichloromethane yielding the dihydroxylated dimer (V). The esterification of both hydroxyls of (V) with 3,4,5-tris(benzyloxy)benzoyl chloride (VI) by means of DMAP in pyridine affords the fully protected target compound (VII), which is finally debenzylated by hydrogenolysis with H2 over Pd/C in methanol/water.

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