Ansa macrolactam

The biosynthesis of R. is stimulated by B-factor and starts from 3-amino-5-hydroxybenzoic acid (C7N-unit), from which the skeleton of the naphthohydro-quinone bridged by a macrolactam is formed via the polyketide pathway. Insertion of oxygen into the ansa-bridge and further functionalization occur later in the biosynthetic sequence. Syntheses of R. have been reported. 

Confalone demonstrated another route through a C-C bond-forming process to form the 19-membered ansa-ring. Closure of this ring was designed so that a dipolar cyclo-addition could be utilized between a simple terminal olefin and nitrile oxide (-C=N -> 0 ), which was provided from a nitroalkane precursor such as 8. A macrolactam ring was cyclized in the form of the isoxazoline product 9. The maytansine model 10 was obtained after reduction and hydrolysis into a P-oxyketone followed by cyclization of the carbamate ring. 

In a total synthesis of the macrolactam herbimycin A, the known mannose-derived epoxide (53) (Vol. 22, p. 150) was converted to (54), and hence to the ansa-chain unit (55). The epoxide ring in (53) was opened regioselectively using disiamyl borane/NaBH4. In a route to glidobamine (56), the core structure of the antibiotic glidobactin, the chirality of the allylic... 

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