新产品编号:1558779

Chemical Name: (1S,2S)-1-(3-Hydroxy-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethane-1,2-diol
项目整合开发状态: Biological Testing
项目研究机构: Arizona State University (Originator), National Cancer Institute (Codevelopment)
合成路线:The CH2Cl2/MeOH extracts of Combretum caffrum stem wood were fractionated using a solvent partition sequence,followed by gel filtration and column chromatography to provide a mixture of three substituted stilbenes: combretastatin A-4 (I),combretastatin A-5 (II) and combretastatin A-6 (III).Further separation of these compounds was achieved via derivatization with tert-butyldimethylsilyl chloride and separation of the respective silyl ethers (IV),(V) and (VI) by preparative TLC.The least polar component (IV) was then desilylated by treatment with tetrabutylammonium fluoride to yield pure combretastatin A-4 (I)

合成路线:The O-silyl stilbene precursor (IV) was also synthesized by the Wittig reaction either between 3,4,5-trimethoxybenzaldehyde (VII) and the phosphonium salt (VIII) or between phosphonium bromide (IX) and 3-(tert-butyldimethylsilyloxy)-4-methoxybenzaldehyde (X),to furnish in both cases a mixture of the target Z-stilbene (IV) and its E-isomer (XI),which were separated by flash chromatography

合成路线:Isovanillin (I) was protected as the silyl ether (II) and subsequently reduced to the benzyl alcohol (III).After conversion of (III) to bromide (IV),its reaction with triphenylphosphine gave phosphonium bromide (V).The ylide resulting from deprotonation of (V) with n-butyllithium was then condensed with 3,4,5-trimethoxybenzaldehyde (VI) to afford the required E-stilbene (VII) along with the corresponding Z-isomer,which were separated by column chromatography.Asymmetric Sharpless dihydroxylation of (VII) by means of AD mix-alpha provided the (1S,2S)-diol (VIII).Finally,desilylation of (VIII) using tetrabutylammonium fluoride afforded the target phenol.