The stereoselective total synthesis of kasugamycin has been completed. 6-Methyl-3,4-dihydro-2H-pyran-2-one (II) was treated with NOCl to give III, which was hydrolyzed to give IV. The catalytic reduction of IV afforded stereoselectively erythro isomer (V), which was lactonized by treatment with Ac_2O, affording VI. The lactone VI was reduced with LiAlH_4 to a hemiacetal (VII), which by treatment with Ac_2O-Py gave VIIIa and VIIIb. The compound (VIIIb) was treated with NOCl to afford the expected chloronitroso dimer (XI). Displacement with lower alcohols such as CH_3OH, EtOH and i-PrOH afforded the corresponding α-glycosides of (XIIa), (XIIb) and (XIIc), respectively. The compound (XIIa) was reduced with hydrogen over Pt, giving XIIIa which gave dl-methylkasugaminide (XIIIc) by subsequent hydrolysis with Ba(OH)_2. Thus, the synthesis of the deoxy-amino sugar moiety of kasugamycin has been accomplished by stereoselective reactions. The compound (XI) was treated with excess of 1:2,3:4-di-O-isopropylidene-d-inositol followed by hydrogenation and hydrolysis. The reaction product was purified by chromatography using Amberlite CG-50 and by recrystallization, affording XIIIb. The synthetic material (XIIIb) was confirmed to be identical with N-acetyl derivative of natural kasuganobiosamine in all respects. Kasuganobiosamine (XIIId) was obtained by further hydrolysis. The synthesis of XIIId completes the total synthesis of kasugamycin, since kasuganobiosamine was previously converted to kasugamycin (I) by treatment with diethyl ester of oxaldiimidic acid and mild hydrolysis with HCl in our structural studies.
