摘要
硫酸西索米星(2)经游离后,用4-硝基苄氧羰基(PNZ)选择性保护6'-位氨基,然后依次用叔丁氧羰基(Boc)保护2'-和3-位氨基,芴甲氧羰基(Fmoc)保护1-位氨基,及Boc保护3"-位氨基得[6'-(4-硝基苄氧羰基)-2',3,3"-三叔丁氧羰基-1-芴甲氧羰基]西索米星(6),再依次经脱除Fmoc、与N-叔丁氧羰基-4-氨基-2(S)-羟基丁酸(12)缩合和脱除PNZ得[2',3,3"-三叔丁氧羰基-1-[N-叔丁氧羰基-4-氨基-2(S)-羟基丁酰基]]西索米星(9),9与苯甲酰氧基乙醛(13)和三乙酰氧基硼氢化钠进行还原氨化制得[6'-苯甲酰氧基乙基-2',3,3"-三叔丁氧羰基-1-[N-叔丁氧羰基-4-氨基-2(S)-羟基丁酰基]]西索米星(10),脱除苯甲酰基保护得[6'-羟乙基-2',3,3"-三叔丁氧羰基-1-[N-叔丁氧羰基-4-氨基-2(S)-羟基丁酰基]]西索米星(11),最后脱除Boc保护得plazomicin(1),总收率3.8%(以2计)。其中10、11未见文献报道。
Plazomicin （1） was synthesized in the following steps： Sisomicin was freed from sisomicin sulfate （2）, then it was selectively protected respectively with 4-nitrobenzyloxycarbonyl （PNZ） at 6＇-amino group, with tert-butoxycarbonyl （Boc） at 2＇- and 3-amino groups, with fluorenylmethoxycarbonyl （Fmoc） at 1-amino group, and finally with Boc at 3＂-amino group to give E6＇-（4-nitrobenzyloxycarbonyl）-2＇,3,3＂-tri-tert-butoxycarbonyl-1- fluorenylmethoxycarbonyl] sisomicin （6）. 6 was subjected to deprotection of Fmoc-group, condensation with N-tert- butoxycarbonyl-4-amino-2 （S） -hydroxybutyric acid （12）, and deprotection of PNZ-group to afford -2＇,3,3＂-tri-tert- butoxycarbonyl-1-[N-tert-butoxycarbonyl-4-amino-2 （S） -hydroxybutyryl]] sisomicin （9）, 9 reacted with benzoyloxy acetaldehyde （13） via reductive amination to give E6＇-benzoyloxyethyl-2＇,3,3＂-tri-tert-butoxycarbonyl-l-EN-tert- butoxycarbonyl-4-amino-2 （S）-hydroxybutyryl]] sisomicin （10）. Then 10 was deprotected to give [6＇-hydroxyethyl- 2＇,3,3＂-tri-tert-butoxycarbonyl-1- [N-tert-butoxycarbonyl-4-amino-2 （S） -hydroxybutyryl]] sisomicin （11）, after deprotection of Boc-group, plazomicin （1） was obtained with an overall yield of 3.8 % （based on 2）. 10 and 11 are new compounds which have not yet been reported in literature.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2017年第5期656-661,共6页
Chinese Journal of Pharmaceuticals
