NOVEL PALLADIUM CATALYZED SYNTHESES OF INDOLE ALKALOIDS

这项建议的长期目标是发展短，温和， 多官能化吲哚的一般和通用合成路线 生物碱 这一方法的关键步骤是最近开发的， 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。 深入研究 将采用各种官能化的2-硝基苯乙烯， 证明了环化的合成通用性和通用性。 具有吲哚核的化合物如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-咔啉， 1，2，3，4-四氢-β-咔啉，吡咯并[4，3，2-de]喹啉， 吡咯并[3，2d]吲哚将被追求。 作为一个展示N- 杂环化反应的多功能性，合成了许多 将寻求具有药理学意义的生物活性吲哚。 例如，全合成（或正式的全合成） 甲氧基山茶毒素（植物毒素和真菌毒素），那西肽（抗生素）， LY-311727（s-PLA 2抑制剂）、BE 10988（拓扑异构酶II抑制剂）、7- bromo-eudistomin D（抗病毒）、蟾蜍胺（致幻剂）、蜘蛛 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.