Clavulanic Acid and Clavams

FOUR-MEMBERED HETEROCYCLIC RINGS AND THEIR FUSED DERIVATIVES 

Clavamycin D 62 R = COCH(NH2)CHMe2 Clavamycin E 63 R = COCH(NH2)Me Clavamycin F 64 R = COCH(NH2)(CH2)3NHAc 

The first study on the biosynthesis of 54, published in 1978, reported that the carbon skeleton of [l,3- C2]-glycerol was incorporated intact into the three p-lactam carbons of 54, namely C-5, C-6, and C-7 [97], 

Some years later, it was reported that also labeled glycerate, propionate, and P-hydroxypripionate were incorporated into C-5, C-6, and C-7 carbons of 54 [98, 99]. Later, it was also noted that the lack of incorporation of the labeled hydrogen present at C-2 of glycerate suggested that the compound was metabolized 

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Tahlan, K., Park, H.U., Wong, A., Beatty, P.H. and Jensen, S.E. (2004) Two sets of paralogous genes encode the enzymes involved in the early stages of clavulanic acid and clavam metabolite biosynthesis in streptomyces clavuligenis. 48, 930-939. 

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