NOVEL PALLADIUM CATALYZED SYNTHESES OF INDOLE ALKALOIDS

这项提议的长期目标是发展短期、温和、 多官能团化吲哚的通用合成路线 生物碱。这种方法的关键一步是最近开发的一种 钯催化的2-硝基苯乙烯的N-杂环化反应 使用一氧化碳作为还原剂。对...的深入研究 各种官能化的2-硝基苯乙烯将被用于 展示环化的综合多功能性和通用性。 合成具有吲哚核的化合物的一般路线，例如2-氟-， 3-氟和2，3-二氟吲哚，吲哚-2-乙酸，吲哚-3- 乙酸、吲哚-3-乙腈、色胺、β-卡宾、 1，2，3，4-四氢-β-咔啉，吡咯并[4，3，2-去]喹啉，以及 将继续研究吡咯并[3，2d]吲哚。作为展示N- 杂环化反应的通用性，合成了许多 将寻求具有生物活性和药理价值的吲哚。 例如，全合成(或正式全合成) 甲氧基喜树碱(植物抗菌素和真菌毒素)、诺西肽(抗生素)、 LY-311727(S-磷脂酶A2抑制剂)，Be 10988(拓扑异构酶II抑制剂)，7- 溴-安非他明D(抗病毒药物)、Bufotenine(迷幻剂)、蜘蛛 提出了毒液(神经毒素)、达米隆C和CC-1065(细胞毒素)。

The long-term objective of this proposal is to develop short, mild, general, and versatile synthetic routes to polyfunctionalized indole alkaloids. The key step in this methodology is a recently developed, palladium catalyzed, N-heteroannulation reaction of 2-nitrostyrenes employing carbon monoxide as the reducing agent. An in depth study of a variety of functionalized 2-nitrostyrenes will be undertaken to demonstrate the synthetic versatility and generality of the cyclization. General routes to compounds having an indole nucleus such as 2-fluoro-, 3-fluoro-, and 2,3-difluoroindoles, indole-2-acetic acids, indole-3- acetic acids, indole-3-acetonitriles, tryptamines, beta-carbolines, 1,2,3,4-tetrahydro-beta-carbolines, pyrrolo[4,3,2-de]quinolines, and pyrrolo[3,2d]indoles will be pursued. As a venue to demonstrate the N- heteroannulation reaction's versatility, syntheses of a number of biologically active indoles of pharmacological interest will be pursued. For example, total syntheses (or formal total syntheses) of methoxycamalexin (phytoalexin and fungitoxin), nosiheptide (antibiotic), LY-311727 (s-PLA2 inhibitor), BE 10988 (topoisomerase II inhibitor), 7- bromo-eudistomin D (antiviral), bufotenine (hallucinogens), spider venoms (neurotoxins), damirone C and CC-1065 (cytotoxins) are proposed.