SYNTHESIS OF ANTITUMOR NATURAL PRODUCTS

抗肿瘤天然产物的合成

• 批准号: 3168356
• 负责人: SAMUEL J DANISHEFSKY
• 金额: $ 32.2万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-03-01 至 1993-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3168356
• 关键词: anomer; antineoplastics; biological products; camptothecin; carboxyl group; chemical structure function; diazo compound; drug design /synthesis /production; epoxides; furans; gangliosides; harringtonines; lactones; mitomycins; neoplasm /cancer pharmacology; sesquiterpenes; sialate; stereochemistry; stereoisomer; steroids; thioamides

A program directed toward the synthesis and bioorganic chemistry of various antitumor natural products is proposed. In this program new synthetic strategies will be explored and new reaction types will be investigated. In the category of the new chemistry to be explored are (a) reactions of diazo compounds with thioamides as a versatile route to enamines, (b) the use of furan surrogates for the anomeric carboxyl function of sialoconjugates, (c) enantiospecific iodolactonizations, (d) the use of epoxyendiolides as external electrophiles, and (e) interactive Lewis acid catalysts. Experiments designed to further clarify the bioorganic chemistry of the mitomycins and camptothecin, as well as sakyomycin are envisioned. New synthetic strategies will be directed toward either the total synthesis or the synthetic modifications of the following natural products: (i) mitomycins, (ii) gangliosides, (iii) pancratistatin, (iv) echinosporin, (v) sakyomycin, (vi) FR 900506, (vii) harringtonines, (viii) camptothecin, (ix) gilvocarcin, (x) tunicamycin, (xi) anguidine and (xii) spicamycin.

一个程序直接对合成和生物有机化学 提出了多种抗肿瘤天然产物的合成方法。 在这个程序中 将探索新的合成策略和新的反应类型 将进行调查。 在新化学的范畴里， 探索的是（a）重氮化合物与硫代酰胺的反应， 烯胺的通用途径，（B）使用呋喃替代物， 唾液酸缀合物的端基羧基官能团，（c） 对映体特异性碘内酯化，（d）使用环氧烯二内酯 作为外部亲电试剂，和（e）相互作用的刘易斯酸催化剂。 旨在进一步阐明生物有机化学的实验 丝裂霉素和喜树碱，以及Sakyomycin， 预想的 新的合成策略将针对总的 合成或合成修饰的下列天然化合物 产品：（i）丝裂霉素，（ii）神经节苷脂，（iii）潘司他汀，（iv） 棘孢菌素，（v）沙康霉素，（vi）FR 900506，（vii）三尖杉酯碱， （viii）喜树碱，（ix）吉尔沃卡辛，（x）衣霉素，（xi） 胍和（xii）穗霉素。