5′-RS-1,5-二氧代-(5′-乙基-5′-羟基-2′H,5′H,6′H-6-氧代吡喃)-[3′,4′,f]-Δ^(6(8))-四氢中氮茚的合成工艺改进

Improved synthesis of 5′-RS-1,5-dioxo-(5′-ethyl- 5′-hydroxyl-2′H,5′H,6′H-6-oxopyrano)- [3′,4′,f]-Δ^(6(8))-tetrahydroindolizine

目的改进喜树碱关键中间体5′-RS-1,5-二氧代-(5′-乙基-5′-羟基-2′H,5′H,6′H-6-氧代吡喃)-[3′,4′,f]-Δ6(8)-四氢中氮茚(1)的合成工艺。方法以6-氰基-1,1-亚乙二氧基-7-(1′-乙氧羰基)丙基-5-氧代-Δ6(8)-四氢中氮茚(2)为原料,经氢化和亚硝化、脱氮、混合金属催化氧化、环合及三氟乙酸脱保护反应得到目标产物。结果与结论新工艺简化了操作、缩短了反应时间,总产率达到了72·4%。

Aim To improve the synthetic process of 5 ′-RS-1, 5-dioxo-（5 ′-ethyl-5′-hydroxy-2′H, 5′H, 6′H-6oxopyrano）-[3′, 4′, f ]- A^6（8）-tetrahydroindolizine, a key intermediate for the total synthesis of camptothecin. Methods The product was synthesized from 6-cyano-1, 1- （ethylenedioxy）-7- [ 1 ′- （ethoxycarbonyl）-propyl]-5-oxo-Δ^6（8）- tetrahydroindolizine by combined hydrogenation and nitrosation, elimination, mixed metal oxidation, cyclization and deprotection. Result and conclusion The intermediate is obtained in an overall yield of 72.4% according to new process, and the operation is simplified.