摘要
本研究报道了一种合成盐酸氨柔比星的新工艺。以(R)-2-乙酰基-2-三氟乙酰胺基-5,8-二甲氧基-1,2,3,4-四氢萘(12)与邻苯二甲酰氯发生傅-克酰化后,经新戊二醇羰基保护、1,3-二溴-5,5-二甲基海因(DBDMH)光化环合和盐酸水解得(7S,9S)-9-乙酰基-9-氨基-6,7,11-三羟基-7,8,9,10-四氢-并四苯-5,12-二酮(6)。6与2-脱氧-1,3,4-三-O-乙酰基-β-D-赤-吡喃戊糖在三氟甲磺酸三甲基硅酯作用下进行糖苷化反应,然后经氢氧化钾脱乙酰基、成盐得目标化合物,总收率10.7%,纯度达99.8%。本工艺操作便捷,后处理简单,产品纯度高。其中,由化合物12制备6的方法未见文献报道。
A new synthetic process of amrubicin hydrochloride was reported. （7S,9S）-9-Acetyl-9-amino- 6,7,11-trihydroxy-7,8,9,10-tetrahydrotetracene-5,12-dione （6） was obtained from （R）-2-acetyl-2-trifluoroacetamido-5,8- dimethoxy-1,2,3,4-tetrahydronaphthalene （12） via Friedel-Crafts acylation with phthaloyl chloride, ketalization of the carbonyl group with neopentylglycol, photochemical cyclization with 1,3-dibromo-5,5-dimethylhydantoin （DBDMH） and hydrolysis with hydrochloric acid sequentially. Then compound 6 was sujected to glycosidation with 2-deoxy-1,3,4- tri-O-acyl-β-D-erythro-pentopyranose in the presence of trimethylsilyl trifluoromethanesulfonate, deprotection of the acetyl groups and salification to prepare amrubicin hydrochloride with a total yield of 10.7 % and a purity of 99.8 %. This process has some advantages such as convenient operation, simple work-up, and high purity, and the synthetic method for compound 6 from 12 has not yet been reported in literature.
作者
游军辉
王俊亮
曹金
余俊
杜祖银
YOU Junhui;WANG Junliang;CAO Jin;YU Jun;DU Zuyin(Jiangsu Hansoh Pharmaceutical Co., Ltd., Lianyungang 22200)
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2018年第7期927-932,共6页
Chinese Journal of Pharmaceuticals
关键词
盐酸氨柔比星
抗肿瘤药
傅-克酰化
光化反应
合成
amrubicin hydrochloride
antineoplastic drug
Friedel-Crafts acylation
photochemical reaction
synthesis
