RESUMEN
The labile tert-butyldimethylsilyl esters of the azetidinones 6-8b served as the crucial synthons in the preparation of the potentially useful ylide pyridyl thio esters 18-20. These intermediates were utilized to synthesize a host of title carbapenems 25-30d, 32, and 49-53. The antimicrobial properties and DHP-I susceptibility of these carbapenems were studied with reference to thienamycin.
Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Antibacterianos/síntesis química , Fenómenos Químicos , Química , Relación Estructura-Actividad , Tienamicinas/farmacologíaRESUMEN
The synthesis of 1 beta-methylcarbapenems having a ROCH2 substituent at the 2-position is described. Their in vitro antibacterial activity and DHP-I susceptibilities are presented.
Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Relación Estructura-Actividad , beta-LactamasRESUMEN
A versatile stereocontrolled total synthesis of thienamycin starting from L-aspartic acid is reported. Stereocontrol is achieved by potassium tri-sec-butylborohydride reduction of a thermodynamically formed 3 alpha-acetylazetidinone intermediate. The key [3.2.0] bicyclic ring system is prepared by a metal catalyzed carbene insertion reaction.
Asunto(s)
Antibacterianos/síntesis química , Tienamicinas , Lactamas/síntesis química , EstereoisomerismoRESUMEN
A regioisomeric set of 2-naphthylcarbapenems featuring cationic substituents was synthesized. Optimal placement of the cationic group was found to markedly improve activity against methicillin-resistant staphylococci while maintaining a good spectrum of gram-negative activity.