3'-Des(diMethylaMino)-3'-keto AzithroMycin synthesis

Yield:-

Reaction Conditions:

with pyridine;sodium hypochlorite;(tetraphenylporphyrine)Fe(III)chloride in dichloromethane;water at 20;

Steps:

4
A solution of 3'-aminoazithromycin (0.90 g) in dichloromethane is treated with 10 mg of 5,10,15,20-tetraphenyl-21H, 23H-porphine iron (III) chloride, an aqueous 5% solution of NaOCl (3 ml) and pyridine (0.025 ml) and the reaction mixture is stirred at room temperature with repeated periodic charges of NaOCl solution (2.5 ml) until starting material content in reaction mixture is lower than 10%. The organic layer is separated and evaporated to dryness to afford 0.94 g of a deep red crude solid. The crude is chromatographed (300 g silicagel 60, 230-400 mesh, 50×5 cm) using hexane:ethyl acetate:diethylamine (10:10:2, by volume) giving 0.176 g of a brown solid which is dissolved in toluene (25 ml). Toluene solution is washed with water (25 ml) at pH 10.5 and 7. Finally, organic layer is extracted twice with water at pH 6 and 5.5. Organic phase is discarded and aqueous layers at pH 5.5 and 6 are combined, the pH adjusted to 11 and extracted twice with isopropyl acetate (50 ml). The organic layer is separated and evaporated to dryness to give 0.098 g of 3'-ketoazithromycin. MS analysis (APCI) of 3'-ketoazithromycin ([m+H] at m/z 720) shows losses of cladinose at m/z 562, cladinose and water at m/z 544, cladinose and modified desosamine at m/z 434, and sequential losses of one water (m/z 416) and two molecules of water (m/z 398) from fragment at m/z 434.

References:

Codony, Albert;Diago, Jose;Garcia, Rafael;Rifa, Jordi US2007/43214, 2007, A1 Location in patent:Page/Page column 5