Erythromycin A. aglycone

Erythromycins. Erythromycin A (14, R = OH, R = CH3, R" = H), the most widely used macroHde antibiotic, was the principal product found in culture broths of Streptomjces eTythreus (39), now reclassified as Saccharopoljspora eythraea (40). It contains a highly substituted aglycone, erythronoHde A, (16, R = R = OH) to which desosamine (1, R = OH, R = H) and cladinose (8, R = CH ) are attached (41). The complete stereochemistry of erythromycin A was estabUshed by x-ray analysis of its hydroiodide dihydrate (42) total synthesis of erythromycin A was a landmark achievement (43), a task previously considered hopeless (44). 

Chemical degradation of erythromycin A yielded its aglycone, erythronoHde A (16, R = R = OH), whereas erythronoHde B (16, R = H, R = OH) was obtained from fermentation (63,64). Biosynthesis of erythromycin proceeds via 6-deoxyerythronoHde B (16, R = R = H) and then erythronoHde B (64,65). The first total synthesis of erythromycin-related compounds was erythronoHde B (66) syntheses of erythronoHde A and 6-deoxyerythronoHde B soon foUowed (67,68). 

The aglycone part of erythromycin A (lb) can be considered as pseudosym-metric (i.e., the stereochemistry of fragment C-4 to C-6 and that of C-10 to C-12 can be regarded as the same). Retro synthetic analysis suggests that the... 

Scheme 7-1. Retro synthetic analysis of the aglycone of erythromycin A (la).

Let us consider Woodward s synthesis of erythronolide A -the aglycone of the antibiotic erythromycin A- which was published posthumously [2]. 

Erythromycin A 64 and spinosyns A and D 65a/65b are important macrolides produced by Saccharopolyspora erythraea and Sacch. spinosa, respectively. Compound 65a contains per-O-methylated L-rhamnose and D-forosamine attached O-glycosidically to the aglycone. Gene knockouts in respective strains as well as expression of various sugar cassettes (along with appropriate GT gene(s)) in Sacch. erythraea mutants led to production of many derivatives of 64 and 65a and tylosin [111-114],... 

Erythromycins, the representative and medicinally important macrolide antibiotics, have been widely studied and are still undoubtedly one of the most challenging target molecules for many synthetic organic chemists (O Fig. 3). Woodward and coworkers accomplished the first total synthesis of erythromycin A (18) in 1981 [8,9,10]. Corey and coworkers synthesized erythronolides A (20) and B (21), the aglycons of erythromycins A (18) and B (19), in 1978 [11,12] and 1979 [13]. 

The commercial product is erythromycin A. which differs from its bio.syntlietic precursor, erythromycin B, in having a hydroxyl group at the 12 position of the aglycone. The chemical structure of erythromycin A was reported by Wiley et al. in I9.S7 and its stereochemistry by Celmer in 1965. An elegant synthesis of erythronolidc A, the aglycone pre.sent in erythromycin A. wa.s described by Corey and associates. ... 

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