硼替佐米的合成工艺改进

摘要

对硼替佐米合成工艺进行优化：以异戊醛与R-（+）-苯乙胺为起始原料经缩合、加成、催化氢化和成盐得到中间体5；另外以L-苯丙氨酸为原料，经酯化、酰化及水解得中间体9；最后中间体5与中间体9经缩合、水解制得目标产物硼替佐米，总收率38.2%(以异戊醛计)。%Intermediate 5 was synthesized from 3-Methyl butanal and (R)-(+)-1-Phenylethylamine by condensation, addition, catalytic hydrogenation and salt-forming. Furthermore, intermediate 9 was synthesized from L-phenylalanine by esterification, acylation and hydrolysis. Finally, the target product, bortezomib was synthesized by condensation of intermediate 5 and intermediate 9 and hydrolysis. The overall yield was 38.2% (based on 3-methyl butanal).