Ruiz-Olalla Andrea, Würdemann Martien A, Wanner Martin J, Ingemann Steen, van Maarseveen Jan H, Hiemstra Henk
Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
J Org Chem. 2015 May 15;80(10):5125-32. doi: 10.1021/acs.joc.5b00509. Epub 2015 May 7.
A general procedure for the synthesis of 1-benzyl-1,2,3,4-tetrahydroisoquinolines was developed, based on organocatalytic, regio- and enantioselective Pictet-Spengler reactions (86-92% ee) of N-(o-nitrophenylsulfenyl)-2-arylethylamines with arylacetaldehydes. The presence of the o-nitrophenylsulfenyl group, together with the MOM-protection in the catechol part of the tetrahydroisoquinoline ring system, appeared to be a productive combination. To demonstrate the versatility of this approach, 10 biologically and pharmaceutically relevant alkaloids were prepared using (R)-TRIP as the chiral catalyst: (R)-norcoclaurine, (R)-coclaurine, (R)-norreticuline, (R)-reticuline, (R)-trimemetoquinol, (R)-armepavine, (R)-norprotosinomenine, (R)-protosinomenine, (R)-laudanosine, and (R)-5-methoxylaudanosine.
基于N-（邻硝基苯亚磺酰基）-2-芳基乙胺与芳基乙醛的有机催化、区域和对映选择性Pictet-Spengler反应（对映体过量率为86-92%），开发了一种合成1-苄基-1,2,3,4-四氢异喹啉的通用方法。邻硝基苯亚磺酰基的存在，以及四氢异喹啉环系统邻苯二酚部分的甲氧基甲基保护，似乎是一种有效的组合。为了证明这种方法的通用性，使用（R）-TRIP作为手性催化剂制备了10种具有生物学和药学相关性的生物碱：（R）-去甲乌药碱、（R）-乌药碱、（R）-去甲网叶番荔枝碱、（R）-网叶番荔枝碱、（R）-三甲氧基喹啉、（R）-阿朴芬碱、（R）-去甲原青藤碱、（R）-原青藤碱、（R）-劳丹碱和（R）-5-甲氧基劳丹碱。
