Macrolide lactams

In another natural product structure determination reported during 2002 that relied on cryoprobe technology, Gustafson et al.244 reported the structure of a new antitumor macrolide lactam, poecillastrin A (108) from the sponge Poecillastra sp. The study was complicated by the need for extensive 1H-13C HMBC data to assemble the structure and a sample of 800 pg (0.55 pmol). 

Actinomycetes are the largest source of natural macrolides. They produce more than three hundred 16-membered macrolides (including spiroacetals) and nearly one hundred 14-membered macrolides (Table III). They also produce various sizes of macrolides up to a 60-membered ring, including polyene macrolides, macrodiolides, macrotetrolides, and immunosuppressive macrolide lactams. Compounds already described in the first edition of this book [1] are mentioned here briefly. 

Fig. 13. Structures of macrolide lactams and a related compound produced by actinomycetes.

Bacteria other than actinomycetes also produce macrolides. About 100 macrolides have been produced by myxobacteria, and about 40 by other bacteria (Tables IV and V). Myxobacteria produce macrolides with up to 42-membered rings including polyene macrolides, macrodiolides, macrolide lactams, and oxazole-containing macrolides. The other bacteria produce macrolides with up to 26-membered rings including polyene macrolides, macrodiolides, and macrotriolides. 

Fig. 16. Structures of macropolylides and macrolide lactams produced by bacteria.

Angiolam A (88) is a 19-membered ring macrolide lactam antibiotic produced by a myxobacterium, Angiococcus disciformis [111]. It inhibited protein synthesis. 

Myxovirescins (myxovirescin Aj = megovalicin C, 89) are macrolide lactam antibiotics isolated from myxobacteria of Myxococcus sp. [112, 113]. Myxovirescin E (90) has a 26-membered ring, and myxovirescin P] (91) and P2 have... 

Cantrell, C. L., Gustafson, K. R., Cecere, M. R., Pannell, L. K., and Boyd, M. R. (2000). Chon-dropsins A and B Novel tumor cell growth-inhibitory macrolide lactams from the marine sponge Chondropsis sp. J. Am. Chem. Soc. 122, 8825-8829. 

Ancorina, Asteropus, Erylus, Melophlus, Pachastrella, Triterpenic glycosides (saponins), steroidal glycosides, macrolide lactams Siliquariaspongia),... 

Rashid, M.A., Gustafson, K.R., and Boyd, M.R. (2001c) New chondropsin macrolide lactams from marine sponges in the genus Ircinia. Tetrahedron Lett., 42,1623-1626. 

Chevallier, C., Laprevote, O., Bignon, J., Debitus, C., Guenard, D., and Sevenet, T. (2004) Isolation of cytotoxic chondropsins, macrolide lactams from the New-Caledonian marine sponge Psammodemma sp. and electrospray ion trap multiple stage MS study of these macrolides. Nat. Prod. Res., 18, 479 84. 

Plaza, A., Baker, H.L., and Bewley, C.A. (2008) Mirabilin, an antitumor macrolide lactam from the marine sponge Siliquariaspongia mirahilis. J. Nat. Prod., 71, 473-477. Additions and corrections, J. Nat. Prod., 72, 324. 

Rashid, M.A., Gustafson, K.R., Crouch, R.C., Groweiss, A., Pannell, L. K., Van, Q.N., and Boyd, M.R. (2002) Application of high-field NMR and cryogenic probe technologies in the structural elucidation of poecillastrin A, a new antitumor macrolide lactam from the sponge PoeciUastra species. Org. Lett., 4, 3293-3296. 

Structural assignment of poedllastrins B and C, macrolide lactams from the deep-water Caribbean sponge Poecillastra species. ]. Nat. Prod., 70, 428 31. 

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