中国药物化学杂志
中國藥物化學雜誌
중국약물화학잡지
Chinese Journal of Medicinal Chemistry
2001年
2期
93-95
,共3页
邓勇%沈怡%钟裕国%唐维高
鄧勇%瀋怡%鐘裕國%唐維高
산용%침이%종유국%당유고
β-内酰胺酶抑制剂%他唑巴坦酸%合成
β-內酰胺酶抑製劑%他唑巴坦痠%閤成
β-내선알매억제제%타서파탄산%합성
他唑巴坦是新颍的β-内酰胺酶抑制剂，以6-APA为原料，经重氮化、溴代等反应制得关键中间体青霉烷酸二苯甲酯-1α-氧化物(4)，与2-巯基苯并噻唑缩合后，经氯代得2β-氯甲基-2α-甲基-6,6-二氢青霉烷酸二苯甲酯(6)，该中间体再经缩合、氧化等步骤得到他唑巴坦酸，总收率16.3%。该法原料易得，反应条件温和，后处理方便，适合大量制备他唑巴坦酸。
他唑巴坦是新潁的β-內酰胺酶抑製劑，以6-APA為原料，經重氮化、溴代等反應製得關鍵中間體青黴烷痠二苯甲酯-1α-氧化物(4)，與2-巰基苯併噻唑縮閤後，經氯代得2β-氯甲基-2α-甲基-6,6-二氫青黴烷痠二苯甲酯(6)，該中間體再經縮閤、氧化等步驟得到他唑巴坦痠，總收率16.3%。該法原料易得，反應條件溫和，後處理方便，適閤大量製備他唑巴坦痠。
타서파탄시신영적β-내선알매억제제，이6-APA위원료，경중담화、추대등반응제득관건중간체청매완산이분갑지-1α-양화물(4)，여2-구기분병새서축합후，경록대득2β-록갑기-2α-갑기-6,6-이경청매완산이분갑지(6)，해중간체재경축합、양화등보취득도타서파탄산，총수솔16.3%。해법원료역득，반응조건온화，후처리방편，괄합대량제비타서파탄산。
A convenient synthesis of tazobactam,a new β-lactamase inhibitor,was described starting with 6-aminopenicillanic acid,which was converted to benzhydryl penicillanate 1α-oxide via diazotization,bromination,oxidation with activated magnesium dioxide in the presence of benzophenone hydrazone and reductive debromination.Then heating with 2-mercaptobenzothiazole,chlorination with sulphuryl chloride gave the 2 β-chloromethylpenam.The reaction with 1H-1,2,3-triazole,oxidation with potassium permanganate gave benzhydryl 2β-〔(1,2,3-triazol-1-yl)methyl〕-2α-methylpenam-3α-carboxylic acid 1,1-dioxide.The deprotection by m-cresol gave tazobactam.The process has the advantages of mild reaction,low cast and convenient aftertreatments.The overall yield was 16.3%.
