Malabarba A, Ciabatti R, Kettenring J, Ferrari P, Scotti R, Goldstein B P, Denaro M
Marion Merrell Dow Research Institute, Lepetit Center, Gerenzano (Varese), Italy.
J Antibiot (Tokyo). 1994 Dec;47(12):1493-506. doi: 10.7164/antibiotics.47.1493.
Removal, by selective reduction, of the acetylglucosamine from teicoplanin A2-2 (CTA/2) produced the 34-de(acetylglucosaminyl)-34-deoxy pseudoaglycone (II). This compound was more active in vitro than CTA/2 against coagulase-negative staphylococci (CNS). Amide derivatives obtained by condensation of the carboxyl group of II with primary amines were particularly active against Streptococcus pyogenes and had some in vitro activity against VanA enterococci highly resistant to both teicoplanin and vancomycin. Among them, a carboxamide (VII) with a branched tetramine also had better activity than the corresponding amide of teicoplanin against CNS. In contrast, the dimethylamide (VIII) of II had little activity against VanA enterococci. While the overall structure of the heptapeptide backbone of the secondary carboxamides of II is the same as in CTA/2 and its amide derivatives, in deoxy pseudoaglycone II and its tertiary amide VIII the 51,52-peptide bond undergoes a conformational change from the original cisoid to the transoid orientation. This difference between the secondary amides of II and dimethylamide VIII is reflected in their different antibacterial spectrum. The direct synthesis of the amides of deoxy pseudoaglycone II from parent CTA/2-amides by reaction with sodium borohydride is also described.
通过选择性还原从替考拉宁A2-2（CTA/2）中去除N-乙酰葡糖胺，得到34-去（N-乙酰葡糖胺基）-34-脱氧假苷元（II）。该化合物在体外对凝固酶阴性葡萄球菌（CNS）的活性比CTA/2更高。通过将II的羧基与伯胺缩合得到的酰胺衍生物对化脓性链球菌具有特别高的活性，并且对替考拉宁和万古霉素均高度耐药的VanA肠球菌具有一定的体外活性。其中，带有支链四胺的羧酰胺（VII）对CNS的活性也比替考拉宁相应的酰胺更好。相比之下，II的二甲基酰胺（VIII）对VanA肠球菌几乎没有活性。虽然II的仲羧酰胺的七肽主链的整体结构与CTA/2及其酰胺衍生物相同，但在脱氧假苷元II及其叔酰胺VIII中，51,52-肽键发生了从原始顺式到反式取向的构象变化。II的仲酰胺与二甲基酰胺VIII之间的这种差异反映在它们不同的抗菌谱中。还描述了通过与硼氢化钠反应从母体CTA/2-酰胺直接合成脱氧假苷元II的酰胺。
