药学与临床研究
藥學與臨床研究
약학여림상연구
PHARMACEUTICAL AND CLINICAL RESEARCH
2014年
2期
121-123
,共3页
纪安成%韩航%王超群%张爱华
紀安成%韓航%王超群%張愛華
기안성%한항%왕초군%장애화
硼替佐米%多发性骨髓瘤%合成
硼替佐米%多髮性骨髓瘤%閤成
붕체좌미%다발성골수류%합성
Bortezomib%Multip lemyeloma%Synthesis
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)。
對硼替佐米閤成工藝進行優化：以異戊醛與R-（+）-苯乙胺為起始原料經縮閤、加成、催化氫化和成鹽得到中間體5；另外以L-苯丙氨痠為原料，經酯化、酰化及水解得中間體9；最後中間體5與中間體9經縮閤、水解製得目標產物硼替佐米，總收率38.2%(以異戊醛計)。
대붕체좌미합성공예진행우화：이이무철여R-（+）-분을알위기시원료경축합、가성、최화경화화성염득도중간체5；령외이L-분병안산위원료，경지화、선화급수해득중간체9；최후중간체5여중간체9경축합、수해제득목표산물붕체좌미，총수솔38.2%(이이무철계)。
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).
