SULFINYL KETIMINES

在涉及对映体选择性合成的研究过程中 生物活性生物碱，我们制备了手性α-亚磺基 凯蒂明。这些酮亚胺的阴离子在原位发生1，4-加成/环 与α-烯酸酯、1，3-二碘丙烷和3-氯-2-丙烷的闭合反应 氯甲基丙烯。我们建议研究不对称加成反应。 各种手性α-亚磺酰基酮亚胺及其取代物的阴离子 无环和环状的α-烯酯和其他亲电体，以及 生成的β-亚氨基亚胺的立体选择性还原和 阿米诺。这些反应在不对称合成中的应用 吲哚里西定[例如，(+)-藜芦碱和(-)-斯拉夫拉明]， 喹啉类[例如，(-)-羽扇豆碱]、吡咯利氮类[例如，(+)-育亨宾 和18，19-二氢乌苏巴林)和β-卡洛林生物碱[例如，(-)- 埃美汀]将进行研究。合成的天然产物，他们的 合成中间体和类似物将进行抗肿瘤活性测试 Dolores Takemoto博士实验室使用的体外组织培养系统 (联合调查员)，以及V.L.Narayanan博士的抗艾滋病活动 国家癌症研究所药物合成与化学分会实验室。 拟议的综合方案是一般性的，应该会提供许多有用的 生物活性合成中间体和类似物。细胞毒性 体外对癌细胞(P388、P815和L1210细胞)的活性， 对正常细胞的毒性及其作用机制(在体外；DNA， 核糖核酸和蛋白质的抑制作用)将会被研究。

In the course of studies involving the enantioselective synthesis of biologically active alkaloids, we have prepared chiral alpha-sulfinyl ketimines. The anions of these ketimines undergo in situ 1,4-addition/ring closure reactions with alpha-ene esters, 1,3-diiodopropane, and 3-chloro-2- chloromethylpropene. We propose to study the asymmetric addition reactions of the anions of various chiral alpha-sulfinyl ketimines and substituted acyclic and cyclic alpha-ene esters, and other electrophiles, and the stereoselective reduction of the resulted beta-sulfinyl enamides and enamines. The utilization of these reactions in the asymmetric syntheses of indolizidines [e.g., (+)-castanospermine and (-)-slaframine], quinolizidines [e.g., (-)-lupinine], pyrrolizidines [e.g., (+)-yohimbine and 18,19-dihydrousambarine], and beta-carboline alkaloids [e.g., (-)- emetine] will be studies. The synthesized natural products, their synthetic intermediates, and analogs will be tested for antitumor activity using in vitro tissue culture systems in Dr. Dolores Takemoto's laboratory (co-investigator), and anti-AIDS activities in Dr. V.L. Narayanan's laboratory, Drug Synthesis & Chemistry Branch, National Cancer Institute. The proposed synthetic schemes are general and should provide many useful biologically active synthetic intermediates and analogues. The cytotoxic activity in vitro against cancer cells (P388, P815, and L1210 cells), the toxicity towards normal cells, and the mechanism of actions (in vitro; DNA, RNA, and protein inhibitions) of these compounds will be studied.