TOTAL SYNTHESIS OF LAVENDAMYCIN & OTHER B-CARBOLINES

该项目有两个目标。 第一是全面综合 抗生素抗肿瘤剂拉文达霉素通过有效的五步 路线 拟议中的计划涉及一个皮克泰-斯宾格勒凝聚的 用β-甲基色氨酸的甲酯官能化醛， 通过脱氢和水解。 醛具有所需的 官能度将通过Diels-Alder缩合制备， 1-氮杂二烯系统与氨基卤醌，然后氧化。 它 应当注意，β-咔啉的四氢衍生物 该系统的一部分（环C）是合成方案中的中间体 并且它也可以是生理活性的。 的第二个目标 项目是将1-氮杂二烯的Diels-Alder反应应用于 β-咔啉及其四氢衍生物的合成， 不太为人所知的化合物在第4位具有取代基， β-咔啉核 合成方案涉及羟醛型 邻硝基甲苯负碳离子与N，N-二甲基腙的缩合反应 以产生相应的腙。 硅烷化 得到氧化的1-氮杂-1，3-二烯体系。 这种二烯与一系列炔属和非炔属的二烯的Diels-Alder缩合反应， 烯属亲二烯体，然后脱甲硅烷基化和Rissert缩合 生成可转化为β-咔啉的氢化咔啉。 取决于所选择的亲二烯体，具有不同的亲二烯体的β-咔啉可用于制备亲二烯体。 将获得在位置4处的取代基。

This project has two objectives. The first is the total synthesis of the antibiotic antitumor agent lavendamycin through an efficient five-step route. The proposed plan involves a Pictet-Spengler condensation of a functionalized aldehyde with methyl ester of Beta-methyltryptophan followed by dehydrogenation and hydrolysis. The aldehyde possessing the required functionalities will be prepared by a Diels-Alder condensation of a 1-azadiene system with an aminohaloquinone followed by oxidation. It should be noted that the tetrahydro derivative of the Beta-carboline portion (ring C) of this system is an intermediate in the synthetic scheme and it may also be physiologically active. The second objective of the project is to apply the Diels-Alder reactions of 1-azadienes to the synthesis of Beta-carbolines and their tetrahydro derivatives, specifically the less-known compounds possessing substitutions at position 4 of the Beta-carboline nucleus. The synthetic scheme involves an aldol type condensation of the o-nitrotoluene carbanion with an N,N-dimethylhydrazone of an Alpha-keto ester to produce the corresponding hydrazone. Silylation of the resulting keto group affords an oxygenated 1-aza-1,3-diene system. The Diels-Alder condensation of this diene with a range of acetylenic and ethylenic dienophiles followed by desilylation and Rissert condensation gives hydro carbolines which can be converted to the Beta-carbolines. Depending on the dienophile chosen, Beta-carbolines with different substituents at position 4 will be obtained.