New straightforward synthesis and characterization of a unique 1β-methylcarbapenem antibiotic biapenem bearing a σ-symmetric bicyclotriazoliumthio group as the pendant moiety
New straightforward synthesis and characterization of a unique 1β-methylcarbapenem antibiotic biapenem bearing a σ-symmetric bicyclotriazoliumthio group as the pendant moiety
复制标题
DOI：
10.1021/jo980462j
复制
发表时间：
1998-11-13
影响因子：
3.6
通讯作者：
Nagao, Y
中科院分区：
文献类型：
--
作者：
Kumagai, T;Tamai, S;Nagao, Y
比阿培南1，（1 R，5S，6S，）-2-[（6，7-二氢-5H-吡唑并[1，2-a][1，2，4]三唑鎓-6-基）硫代]-6-[（R）-1-羟乙基]-1-甲基碳青霉烯-2-烯-3-羧酸酯，是一种新型非天然1 β-甲基碳青霉烯类抗生素，具有广泛的抗菌活性，化学稳定性好，对人肾脱氢肽酶-I具有广泛的稳定性。从水合肼3开始，沿着沿着一条经济可行的合成路线，成功地合成了可用于1的侧基部分的氯化巯基双环三唑鎓 2。硫醇2被有效地用于比阿培南1的快速合成。通过X-射线衍射、H-1 NMR和氘代实验研究了化合物1的结构（晶体结构、非键S-O相互作用、构象分析和CH-O氢键）。
Biapenem 1, (1R,5S,6S,)-2-[(6,7-dihydro-5H-pyrazolo[1,2-a][1,2,4]triazolium-6-yl)thio]-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate, is a new non-natural 1 beta-methylcarbapenem antibiotic which exhibits a wide range of antibacterial activity, remarkable chemical stability, and extensive stability against human renal dehydropeptidase-I. Mercaptobicyclotriazolium chloride 2 useful for the pendant moiety of 1 was successfully synthesized starting from hydrazine hydrate 3 along an economically available synthetic route. The thiol 2 was efficiently exploited for an expeditious synthesis of biapenem 1. Characterization (crystal structure, nonbonded S---O interaction, conformational analysis, and CH- - -O hydrogen bonds) of 1 was investigated by its X-ray crystallographic, H-1 NMR, and deuteration experiment analyses.