Macrolide antibiotics, 16-membered tylosin derivatives

HA Kirst, M Debono, KE Willard, BA Truedell, JE Toth, JR Turner, DR Berry, BB Briggs, DS Fukuda, VM Daupert, AM Felty-Duckworth, JL Ott, FT Counter. Preparation and evaluation of 3,4"-ester derivatives of 16-membered macrolide antibiotics related to tylosin. J Antibiot 39 1724-1735, 1986. 

Diastereoselective hydroboration reactions of olefins possessing homo-allylic stereogenic centers additionally can be a preparatively useful process. For example, the hydroboration of 69 with diborane proceeded with high diastereocontrol to provide the aldehyde 70 (Scheme 7.12). This served as an advanced intermediate in Nicolaou s route to 0-mycinosyltylonolide (71), a monosaccharide derivative of the 16-membered macrolide antibiotic tylosin [28]. 

Several 16-membered macrolides form metabolites which retain antimicrobial activity. As discussed above, 3"-esters such as rokitamycin and miokamycin produce prolonged concentrations of antibiotic in vivo due to the facile 3"- to 4"-0-acyl migration that follows enzymatic removal of the original 4 -ester [34, 269, 270], Following a different approach to overcome the lability of 4"-esters, specific 4"-0-acyl derivatives of tylosin were selected from the series of esters (15) based upon their greater stability toward liver enzymes [80], Although esterases play the most prominent role in metabolism of 16-membered macrolides, other mechanisms such as oxidative hydroxylation, A-demethylation, reduction, and hydrolysis of sugars have been reported for various compounds [91, 96, 115, 259, 270-272]. 

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