Nargenicins macrolides

The second example [Scheme 2.126] shows how a latent carboxyl function was released from the a-hydroxyoxazoline by /V-methylation to give an iminium salt that was then hydrolysed to an advanced intermediate in a synthesis of the macrolide antibiotic Nargenicin.257... 

Recently, workers at Abbott Laboratories reported the isolation and prelintinary characterization of a new nargenicin-type Z u-macrolide antibiotic, coloradocin, 8, from cultures of Actinoplanes coloradoensis. H The novel bislactonic structure proposed for 8 was based on a detailed spectroscopic examination which included extensive homo- and heteronuclear 2D NMR studies. 12 Although these investigations failed to unequivocally define the relative configuration of the macrocyclic chirality, the key structural elements of 8, including an oxa-bridged octalin... 

As part of an effort to prepare compounds for correlation with advanced synthetic intermediates, Plata examined the stepwise degradation of the nargenicin C19-C14 macrolide subunit.21 Following the earlier work of Whaley,3 ester 20 was subjected to periodate oxidation and the remaining C9 and Cll hydroxyls protected as methoxymethyl ethers (Figure 9). 

All 10-membered ring macrolides have skeletons similar to nargenicin A, (3) [9]. The skeleton of luminamicin (= coloradocin, 4) has an additional two fused rings, and the position of the epoxide bridge on decalin differs from that of 3 [10, 11]. Compound 4 showed antibacterial activity against anaerobic bacteria, especially against Clostridium sp. 

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