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

I.甘露糖胺A和动力霉素的不对称全合成方法AI)通过二氢吡啶酮的Diels-Alder反应合成了甘露糖胺A(1)的四环核心。2)以L丝氨酸为原料，经Diels-Alder反应，与硅氧二烯发生Diels-Alder反应，再经一系列新的和常规的反应路线，合成了具有光学活性的四环核甘氨酰胺A。3)以二氢-2-喹啉酮为原料，在Lewis酸催化下，与2-三甲基硅氧基-1，3-丁二烯和2-三甲基-1，3-戊二烯进行Diels-Alder反应合成了1-甲氧基羰基-3-苯硫基-2-喹啉酮。将D-A加合物转化为9-菲咯烷酮缩酮将开辟一条合成动力霉素A核心结构的新途径。在三烷基铝(1/3摩尔当量)存在下，用酸性氯化物与三烷基铝(1/3摩尔当量)反应，有效地合成了α，β-不饱和酮。II.以L-丝氨酸为原料，立体选择性地合成了L-苏氨酸、D-ervthro-1-phenyl-2-palmitoylamino-3-morpholino--1-丙醇(PPMP)和十酰基衍生物(PDMP)。以二异丙基苯基氯硼烷为手性Lewis酸催化剂，使Nb-羟色胺与醛发生Pictet-Spengler反应，得到相应的2-羟基四氢-β-咔啉，最高可达90%ee。手性联萘酚衍生的Brphindted酸辅助Lewis酸催化的Pictet-Spengler对映体选择性反应的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.