RSL3中间体的简便合成

A Convenient Synthesis of RSL3 Intermediate

摘要:

以D-色氨酸为原料，通过酯化、Pictet-Spengler两步反应，简便有效地合成了RSL3的关键中间体(1S,3R)-1-[4-(甲氧羰基)苯基]-2,3,4,9-四氢-1H-吡啶[3,4-b]吲哚-3-羧酸甲酯盐酸盐。对Pictet-Spengler反应条件进行了考察。结果表明：当n(D-色氨酸甲酯盐酸盐):n(4-甲酰基苯甲酸甲酯)=1:1.1、乙腈为反应溶剂，回流反应6 h，通过减压抽滤即可得到trans-构型产物（RSL3中间体）。产物及中间体经过1HNMR，1H-1H NOESY和ESI-MS进行确认。

Abstract:

(1S, 3R)-methyl 1-(4-(methoxycarbonyl)phenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3- carboxylate hydrochloride, the key intermediate of RSL3, was synthesized by an efficient and parctical method from D-Tryptophan through a two-step reaction, involving esterification and Pictet-Spengler reaction. The Pictet-Spengler reaction conditions were investigated, and the optimal conditions were as follows: the molar ratio of D-tryptophan methyl ester hydrochloride and methyl 4-formylbenzoate is 1:1.1, the mixture was stirred in acetonitrile and refluxing for 6 h. The trans-isomer (RSL3 intermediate) was obtained by suction filtration. The structures of intermediate and the product were confirmed by 1HNMR, 1H-1H NOESY and ESI-MS.