Sugar moieties, erythromycins

The macrolides are a group of closely related compounds characterized by a macrocyclic lactone ring (usually containing 14 or 16 atoms) to which deoxy sugars are attached. The prototype drug, erythromycin, which consists of two sugar moieties attached to a 14-atom lactone ring, was obtained in 1952 from Streptomyces erythreus. Clarithromycin and azithromycin are semisynthetic derivatives of erythromycin. 

It was further proposed that mycarose is first added to erythronolide B. This step is followed by 1. the addition of the amino sugar moiety, 2. the methylation of mycarose to cladinose in the cases of erythromycins A and B and 3- the introduction of an hydroxyl group at C-12 in the cases of erythromycins A and C. These last three steps do not necessarily occur in the order given. 

The O-methyl group of L-cladinose (2) is also derived from L-methionine. The O-methylation step does not, however, take place at the level of the nucleotide-sugar, but it occurs when the substrate is erythromycin C, which contains L-mycarose and D-desosamine as glycosidic components9 (see Scheme la). The O-methylation of the L-mycarose moiety of erythromycin C by a partially purified enzyme from Streptomyces erythreus was described by Alpine and Corcoran.10,11 The reaction catalyzed is shown in Scheme la. 

---