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The synthesis and in vitro antimicrobial activity of a new synthetic carbapenem, (5R,6S)-6-[(R)-1-hydroxyethyl]-2-[(S)-l-acetimidoylpyrrolidin-3-ylthio]-l-carbapen-2-em-3-carboxylic acid (RS-533), are described. The MIC values of related penems and carbapenems are also given for comparison with those of the new carbapenem.The discovery of the potent broad-spectrum antibiotic thienamycin (THM)1`4) has arisen chemical and microbiological interest in carbapenems and structurally related penems. Extensive molecular modifications of THM and penems have been made in pursuit of greater stability and potency and, as a result, clinically useful lactams, N-formimidoylthienamycin (MK0787)1-7) and an oral penem (Sch 29482)8) have been obtained. Prior to the present work on carbapenems, we were concerned with the synthesis9,10) and bioassay of new penems, during which we discovered 6-(1-hydroxyethyl)-2-(pyrrolidin-3-ylthio)penem-3-carboxylic acids (R-1 and S-1)11,12) which were found to have potent in vitro activity comparable to THM. This finding led us to synthesize carbapenem congeners in the expectation that the carbapenems would display greater activity than either the penems or THM. As a result of extensive syntheses ranging from penems to carbapenems, we ultimately obtained a new carbapenem, RS-533; one of the most promising antibiotics in view of the potent in vitro and in vivo activity13) against a wide range of bacteria. SynthesisIn preparing the desired carbapenern compound, we utilized the 2-oxocarbapenam (9b), first synthesized by the Merck group,14) as the most reliable intermediate for carbapenem synthesis. Although 9a and 9b have been synthesized by way of the Q-keto esters (4a and 4b) by several routes,15-18) we prepared 4a and 4b starting from the acetoxyazetidinone (2) and the 3-pyrrolidinocrotonic acid esters as shown in Chart 2.

Treatmentof 10-chloro-2,3,5,6,7,11b-hexahydro-7-methyl-11b-phenylbenzo [6,7] -1,4-diazepino [5,4-b]oxazol-6-one (IV) with sodium hydride in dimethyl acetamide gave the two compounds, 6-chloro-3-(2-hydroxyethyl)-1-methyl-4-phenyl-2(1H)-quinolone (V) and 6-chloro-3-hydroxy-1-methyl-4-pherryl-2(1H)-quinolone (VI). A mechanistic assumption for the formation of V was discussed.In the past few years, it has been reported that 1,4-benzodiazepines undergo rearrangements leading to isoindoles,1,3) indoles,4) quinazolines,5-7) quinoxalines8) and quinolines.9)In the preceding paper, we have reported1 on the base-catalyzed intramolecular rearrangements of benzo [6,7]-1,4-diazepino [5,4-b] oxazoles giving isoindole and acridanone derivatives, and on the reactions of I with N,N-dimethyl formamide (DMF) in the presence of sodium hydride affording exo-methylene compounds as shown in Chart 1. Our interest in the for-

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