β-内酰胺族抗菌素的研究——Ⅲ.7-脒硫乙酰胺基头孢菌素酸亚砜衍生物的立体定向合成

STUDIES ON β-LACTAM ANTIBIOTICS——Ⅲ. THE STEREOSPECIFIC SYNTHESIS OF 7-AMIDINOTHIOACETAMIDOCEPHALOSPORANIC ACID SULFOXIDE DERIVATIVES

摘要: 为寻找更有效的新头孢菌素衍生物,本文报道了具脒硫基侧链的头孢菌素酸(R)和(S)型亚砜的立体定向合成。(S)-型亚砜衍生物II-(S)系将化合物V直接用过酸氧化,再与各种取代硫脲缩合而得。若将7-ACA转化为Schiff碱再行氧化则可立体定向地合成(R)-型亚砜Ⅶ,继而水解,酰化得Ⅸ。最后与各种取代硫脲缩合可得(R)-亚砜衍生物Ⅱ-(R)。所得各中间体及产物的立体化学均经₁H核磁共振予以证实。

Abstract: In order to find more active new cephalosporins a series of R- and S-sulfoxides of 7-(N, N'-substituted amidinothioacetamido) cephalosporanic acid was synthesized stereospecifically. The S-form sulfoxides Ⅱ-S were Prepared by oxidation of intermediate V with hydrogen peroxide and acetic acid and then condensation with a Variety of substituted thiourea. The R-form sulfoxides Ⅱ-R were prepared by several steps. After conversion of 7-ACA Ⅲ into corresponding Schiff's base the R-form sulfoxide of the Schiff's base was formed by oxidation. The intermediate Ⅸ was obtained by hydrolysis and acylation. The dersired derivatives Ⅱ-R could be prepared by condensation conveniently with N, N'-substituted thiourea.The stereochemistry of new cephalosporanie acid derivatives and intermediates has been idendified by means of ¹H NMR.