66 アプラマイシンの全合成

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A potent aminoglycoside antibiotic, apramycin (1), has been stereoselectively synthesized from neamine through the aminooctodiose derivative, aprosamine (22). The N-oxide 3, which was derived from the masked neamine 2, was treated with benzoyl chloride and diisopropylethylamine to give the aldehyde 4. Addition of allylmagnesium chloride to 4 provided 6'S- and 6'R-isomer (5 and 6). Oxidation of 5 followed by selective removal of the cyclic acetal group afforded the octodiose derivative 7, which was in turn converted by our method into the glycal 11. The other isomer 6 was also efficiently transformed into 11 through the inversion of the 6'-hydroxyl group (6→12→13→11). Azidonitration of 11 gave the 7'-azido compounds 14 and 15, which were converted into the methyl β-glycoside 16 by alkaline treatment in methanol. In a straightforward fashion 16 was transformed into 17, which was mesylated to 18. Selective chlorination and dechlorination of 18 gave the 3'-deoxy compound 19. Epimerization of the 6'-hydroxyl group was accomplished by treatment of 19 with sodium acetate to afford the cis-cyclic carbamate 20. Successive deprotection of 20 gave the aminooctodiose derivative, methyl β-aprosaminide (21), which was further hydrolyzed to give aprosamine (22). The glycosidation of the key intermediate 23 with 4-azido-2,3,6-tri-O-benzyl-4-deoxy-β-D-glucopyranosyl fluoride was realized under modified Mukaiyama conditions to give the desired glycoside 24. Hydrogenolysis of 24 completed the synthesis, giving apramycin (1) identical with the natural antibiotic.
天然有機化合物討論会の論文
1983-09-15

66 アプラマイシンの全合成

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