Synthetic Study of Antitumor Panaxytriol in Panax ginseng

• Main Authors: Jui-Hung Wu, 吳瑞鴻
• Other Authors: Hsi-Jung Yu
• Format: Others
• Language: en_US
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/39522448093305059648

碩士 === 中國文化大學 === 應用化學研究所 === 89 === Panax ginseng has been considered as one of the most important and valuable medicinal plants in traditional oriental medicine. It was reported to have numerous biological activity, including effects on the cardiovascular, immune, and nervous systems, and activity as an antidote, antitumor agent, or antitumor adjuvant and as an antidiabetic. Although ginseng has been used for thousands of years, its chemical constituents were gradually isolated until 1960s. In the last two decades, many unusual polyacetylene compounds were isolated from this traditional medicine and showed to suppress the in vitro growth of cultured tumor cells. Panaxytriol is one of these new type of antitumor agents. In this thesis, the asymmetric synthesis of panaxytriol was investigated. We started with trans-2-decenal, which was reduced to trans- dec-2-en-1-ol by DIBAL. Phosphorus tribromide converted the alcohol into an allyl bromide and the bromide coupled with lithium acetylide in the presence of copper(I) cyanide to give trans-dodec- 4-en- 1-yne. Sharpless asymmertric dihydroxylation with AD-mix-β transformed the enyne into (4R,5R)-dodec-1-yne-4,5-diol,which was one of the precursors for the synthesis of panaxytriol. The other precusor, 5-iodopent-1-en-4-yn-3-ol, was syn- thesized by two approaches. One approach started with propenal, which reacted with lithium trimethylsilylacetylide to produce 5- trimethylsilylpent-1-en-4-yn-3-ol. The reaction of this enynol with N-iodosuccinimide and AgNO3 gave 5-iodopent-1-en-4-yn-3-ol. Finally, if the iodoacetylene couples with (4R,5R)-dodec-1-yne-4,5- diol using Cadiot-Chodkiewicz procedure, panaxytriol will be obtained, which has the configuration of 3R,9R,10R and 3S,9R,10R. The other approach started with methyl 3,4-O-iso- propylidene-L-threonate. After protection of the hydroxyl group with tert-butyldimethylsilyl chloride, the ester was reduced by DIBAL to give an aldehyde, which reacted with dimethyl 1-diazo-2- oxopropylphosphonate to afford an alkyne. Finally, the alkyne will be converted into (R)-5-iodopent-1-en-4-yn-3-ol in three steps and then couple with (4R,5R)-dodec-1-yne-4,5-diol by Cadiot- Chodkiewicz procedure to give (3R,9R,10R)-panaxytriol. In this synthetic study of panaxytriol, 5-iodopent-1-en-4-yn-3- ol and(4R,5R)-dodec-1-yne-4,5-diol were successfullys ynthesized. In addition to racemic 5-iodopent-1-en-4-yn-3-ol, the synthesis of (R)-5-iodopent-1-en-4-yn-3-ol was also attempted. The precursor for the synthesis of panaxytriol, (4R,5R)-dodec-1-yne-4,5-diol, was synthesized via only four steps, which was much fewer than the procedures reported in the synthesis of the alkynediol precursor.