Nocardia uniformis Nocardicins

The simple nonfused 3-lactam ring is encountered in a number of natural structures, such as the nocardicins, e.g. nocardicin A (Figure 7.45), from Nocardia uniformis, and the so-called monobactams (monocylic P-lactams) based on the structure shown in Figure 7.39, which was... 

Serine is the precursor of several antibiotics. The oxazole ring of the antibiotic virginiamycin Mj 100(Scheme 31)is derived from serine incubation of Streptomyces virginiae with samples of (2S, 3R)- and (2S, 3S)-[3- Hi]serine, derived as in Scheme 18, showed that the 3-pro-S hydrogen of serine is lost on formation of the double bond (107). This implies anti dehydrogenation, a process more commonly found to be syn. The -lactam antibiotic nocardicin 101 is biosynthesized from serine, and incubation of Nocardia uniformis with stereospecifically deuterated serines, prepared by the method outlined in Scheme 21, has yielded samples of norcardicin, the NMR spectra of which indicated that ) -lactam ring formation occurs with inversion of configuration (108, 109). 

The nocardicins are a family of monocyclic BLAs produced by the actinomycete Nocardia uniformis subsp. tsuyamanensis ATCC 21806, first isolated in 1976. Nocardicin A is the major product, with several other structurally related metabolites in smaller amounts, nocardicins B-G (Figure 4.14). Nocardicin A was the first member of this family to be reported [52]. In the same year, the isolation of nocardicin B was also reported [53]. The structures 29 and 30 were soon assigned to nocardicin A and B, respectively [54,55]. One year later, the isolation of nocardicins C-G was reported, and the assignment of the structures 31-35 were proposed in the same paper [56]. Nocardicin A has also been isolated from the actinomycetes Actinosynnema mirum [57], Nocardiopsis atra [58], and Microtetraspora caesia [59]. The nocardicins were the first naturally occurring monocyclic p-lactams that display any significant antibacterial activity to be isolated, and they bear structural... 

In a biosynthetic study, the stereochemical course of 3 lactam formation in Nocardicin A was established (5). By introducing H-labeled serine into cultures of Nocardia uniformis the sites of enrichment were easily determined by NMR (Figure 6). The crucial points in the study were the possibilities to distinguish sites A and B (Figure 6) and to follow their evolution from the precursor. The precursor, stereospecifically... 

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