6 Spiro epoxypenicillins

Bycroft et al. [83] have prepared a series of novel 6-spiro-epoxypenicillins 43,44 (Scheme 12) by the reaction of diazopenicillanate 41 with oxalyl chloride followed by reactions with various nucleophiles. These compounds notably exhibit (i-lactam inhibitory and antibacterial properties [84] depending on substituents and stereochemistry of epoxides. These inhibitors possess side-chains, which are highly con-formationally restricted but structurally similar to those of some active penicillins. 

Scheme 12 Synthesis of series of 6-spiro-epoxypenicillins by use of diazopenicillanate and oxalyl chloride...

Bycroft et al. [83] have reported a series of semisynthetic penicillin derivatives such as, 6-spiro-epoxypenicillins F, G (Fig. 8) possessing both (3-lactamase inhibitory and antibacterial activity (Fig. 8). It has been found that novel chlorinated 6-spiro-epoxypenicillins F are potent in vitro inhibitors of a range of chemically important (3-lactamases [84], whereas, 6-spirocyclopropylpenems, G, show a reduced level of (3-lactamase inhibitory activity. The significance of the five fold difference between the turnover numbers for F(a) and G(b) (differ only in their stereochemistry at one center) was found to be in close comparison with the turnover number of 20,000, reported for the established (3-lactamase inhibitor, sulbactam [140]. Thus, the notable (3-lactamase inhibitory and antibacterial properties of these spiro-(3-1 actams depend upon the substituents and the stereochemistry of the epoxide. 

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See also in sourсe #XX -- [ , ]

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