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[摘要]：The 2-amino-2-deoxy-alpha-D-glucopyranosyl moiety (ring 1) of paromomycin was replaced by a 2,4-diamino-2,4-dideoxy-alpha-D-glucopyranosyl, 2,4-diamino-alpha-D-galactopyranosyl, 2-amino-2-deoxy=alpha-D-galacto[yranosyl, or 3,4,5-trideoxy-4-aza-alpha-D-erythro-heptoseptanosyl moiety to investigate the effect of the substituent at C(4') on the interaction with ribosomal RNS. The triflate 6 was prepared from the key intermediate pentaazido 3',6'-dibenzyl ether 5, and the hexosulose 10 was obtaines by oxidation of 5 with Dess-Martin's periodinane. Stereoselective reduction of 10 with NaBH4 gave the alcohol 11 that was trnasformed into the triflate 12. The epiemeric hexaazides 7 and 13 were obtaines by treating the triflates 6 and 12, respectively, with tetrabutylammonium azide. Periodic clevage of glycol 2 yielded the dialdelhyde 24 that was reductively aminated with aniline and benzulamine to give the 3,4,5-trideoxy-4-aza-alpha-D-erythro-heptoseptanoside 25 and 26, respectively. Standard azide reduction and debenzylation yielded 9 (2,4-diamino-2,4-dideoxy-alpha-D-galactopyranosyl ring 1), 13 (2-amino-2-deoxy-alpha-D-galactopyranosyl ring 1), 17 (2,4-diamino-2,4-dideoxy-alpha-D-glucopyranosyl ring 1), and 27 and 28 (3,4,5-trideoxy-4-aza-alpha-D-erythro-heptiseptanosyl ring 1). The derivaticves 9 and 13 possesing a D-galacto-configured ring i were less active than the corresponding D-gluco-analogues 17 and paromomycin (1), respectively. The C(4')-aminodeoxy derivatives 17 (D-gluco ring 1) and the known 4'-deoxyparomomycin (23), prepared by anew route, displaying slightly lower antibacterial activities than paromomycin (1). Cell-wall permeability is not responsible for the unexpectedly low activity for 17, as shown by cell-free translation assays. The results evidence that the orientation of the substituent at C(4') is more important than its nature for drug binding and activity. |
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