SYNTHESIS AND DESIGN OF ANTITUMOR NITROGEN CONTAINING NATURAL PRODUCTS-STUDIES BASED ON NATURAL PRODUCTS AS PROBES OF BIOLOGICAL FUNCTION-

1 . manzamine A和dynemicin的对映选择性全合成方法)通过二氢吡啶酮的Diels-Alder反应合成了manzamine A(1)的四环核心。两个D-A产物通过常规途径转化为关键三环酮，并开发了新的途径。2)通过l -丝氨酸衍生的二氢吡啶酮与硅氧二烯的Diels-Alder反应，通过一系列新的和传统的途径合成了具有高立体选择性的光活性四环核心的Manzamine A。3)以二氢-2-喹啉酮为原料制备了1-甲氧基羰基-3-苯基硫代-2-喹啉酮，并在Lewis酸催化下与2-三甲基硅氧基- 1,3 -丁二烯和2-TMSO- 1,3 -戊二烯进行了diols - alder反应。D-A加合物转化为9-菲苯三啶酮酮将开辟一条新的合成途径，以获得动力蛋白a核心结构。我们发现在AlC13（1摩尔当量）存在下，酸性氯化物与三烷基铝（1/3摩尔当量）反应可有效合成a， β -不饱和酮。以l-丝氨酸为原料，立体选择性合成了l-三o和d -ervthro-1-苯基-2-棕榈酰氨基-3-morpholino- 1-丙醇（PPMP）及其癸醇衍生物（PDMP）。通过x射线分析确定了Vsr内切酶的晶体结构。首次实现了试剂控制的对映选择性Pictet-Spengler反应。以二异戊二苯氯硼烷为手性Lewis酸催化剂，通过nb -羟色胺与醛的Pictet-Spengler反应，以高达90%的ee生成相应的2-羟基四氢- β -碳胺。手性双萘酚衍生的brphindindted酸辅助Lewis酸催化了Pictet-Spengler反应，ee高达91%。

I.Enantioselective total synthetic approaches to manzamine A and dynemicin AI) Synthesis of the tetracyclic core of manzamine A (1) was achieved via Diels-Alder reaction of the dihydropyridinones. Conversion of the two D-A products to the key tricyclic ketone was conducted through a conventional pathway as well as a new pathway developed.2) The highly stereoselective synthesis of the optically active tetracyclic core of Manzamine A was achieved via the Diels-Alder reaction of dihydropyridinone, derived from L-serine, with siloxydienes, followed by sequential new and conventional pathways.3) Preparation of the 1-methoxycarbonyl-3-phenylthio-2-quinolinone from dihydro-2-quinolinone and its Diels-Alder reaction with 2-trimethylsilyloxy- 1, 3-butadiene and 2-TMSO- 1, 3-pentadiene under Lewis acid catalyst was developed. Conversion of the D-A adduct to 9-phenanthridinone ketal will open a new synthetic route to a dynemicin A core structure.4). We found an efficient synthesis of a, beta-unsaturated ketones by the reaction of acid chlorides with trialkylaluminum (1/3 mole equiv) in the presence of AlC13 (I mol equiv).II.Both L-threo and D-ervthro-1-phenyl-2-palmitoylamino-3-morpholino- 1-propanol (PPMP) and the decanoyl derivative (PDMP) were synthesized stereselectively from L-serine.III.The crystal structure of Vsr endonuclease was determined by X-ray analysis.IV.The first example of a reagent-controlled enantioselective Pictet-Spengler reaction was achieved. Using diisopinocampheylchloroborane as a chiral Lewis acid catalyst, the Pictet-Spengler reaction of Nb-hydroxytryptamine with aldehydes gave the corresponding 2-hydroxytetrahydro-beta-carbolines in up to 90% ee. The enantioselective Pictet-Spengler reaction catalyzed by chiral binaphthol-derived Brphindted acid-assisted Lewis acids, with up to 91% ee, was also achieved.