Partial structure of 4-epi-tetracycline

Parfial sfrucfure of nafural fefracycline

Scheme 4.7 Epimerisation of tetracyclines.

at pH 3.2) and is also catalysed by phosphate and citrate ions.

Cephalosporin esters are widely used as intermediates in cephalosporin synthesis and as prodrugs for oral administration of par-enteral cephalosporins. These esters undergo reversible base-catalysed isomerisation according to the mechanism shown in Scheme 4.8. A proton in the 2-position is abstracted by a base (B) and the resulting carbanion can be repro-tonated in the 4-postion, giving a A 2-ester. On hydrolysis, A 2-cephalosporin esters yield A 2-cephalosporins, which are biologically inactive.

Cis-trans isomerisation may be a cause of loss of potency of a drug if the two geometric isomers have different therapeutic activities. Vitamin A (all-trans-retinol) is enzymatically oxidised to the aldehyde and then isomerised to yield 11-cis-retinal (Scheme 4.9), which has a decreased activity compared with the all-trans molecule.

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