Oleandomycin methods

Cyclization via intramolecular olefination of complex phosphonates remains the most important method of synthesis for complex natural macrocycles. Examples include syntheses of 20-membered macrolide antibiotic, aglycones of venturicidins A and B,108 oleandomycin (a 14-membered macrolide antibiotic), 109 the 19-membered macrocyclic antibiotic, anti-tumour agent (-t-)-hitachimycin,ll0 and the macrocyclic lactones (183).1H Cyclization of the phosphonate (184) under Masamune-Roush conditions has been used to synthesize the 28-membered macrolactam myxovirescin B.112... 

Spagnoli, R. Cappelletti, L. (1981) New screening method for rapid identification of blocked mutants application to erythromycin- and oleandomycin-producing strains. 

Tatsuta s oleandomycin synthesis is based on the construction of the aglycone by coupling of the C1-C7 (131) and Cg-Ci3 (136) segments, which are derived from L-rhamnose and (S)-( + )-methyl 3-hydroxy-2-methylpropionate, respectively, and on the stereo- and regioselective introduction of the two sugar moieties. Methods for selective esterification and for the synthesis of 2-deoxy-a-glycosides were developed in the course of the synthesis. 

For the quantitative determination of erythromycin and oleandomycin in animal tissues, milk, and eggs, a TLC method has been described (44) in which 25 g of sample are homogenized with 90 ml of acetonitrile and 2 ml of saturated sodium carbonate solution and centrifuged. Then 3 g of sodium chloride are added to the supemate and the extraction is done with 50 ml of dichloromethane. The organic layer is dried with 5 g of anhydrous sodium sulfate, filtered through cotton wool, evaporated to dryness, and dissolved in ethyl acetate, followed by different washing steps. 

The chiral pool refers to readily available optically active natural products, some of which are commercially used in quantities of 10 -10 tonnes per year [5], Among them, the most inexpensive compounds are a-amino acids, like monosodium L-glutamate, or carbohydrates, like dextrose or sorbitol. The success of the second method depends on the availability of particular catalysts. One rather special example, how efficient stereoselective synthesis can work, is the syn-selective aldol reaction followed by a stereoselective alkene hydroboration and ketone reduction (Figure 1.8) which were used by Paterson et aJ. [26] to synthesize intermediates for the antibiotic oleandomycin. According to Paterson et al., four new stereocenters are formed in only two synthetic steps [9]. For the purpose of separating racemic mixtures... 

Three papers have reported on glycosylations of macrocyclic compounds. Mycinamycin IV (25), containing mycinose and desosamine, was made by the glycosylation methods noted in references 11 and 12, and oleandomycin (26) has been synthesised... 

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