CARB 84 |
| Our group has been working on the synthesis of novel aminoglycosides with activity against modifying enzymes. We recently synthesized a 3',4'-dideoxypyranmycin analog, RR501 which had impressive antibacterial activity against bacteria that harbor one modifying enzyme, APH(3')-I. In an attempt to further improve the activity of this dideoxy analog, we have dedicated our synthetic efforts toward the attachment of ((S)-2-hydroxy-4-aminobutyrl) (AHB side chain) at the N-1 position. Amikacin, a kanamycin derivative with AHB at N-1, has very impressive activity against resistant bacteria. We have developed a novel method to selectively reduce the N-1 azido group of the dideoxyneamine. It has been shown that the electron-deficient azido group will have greater reactivity toward the Staudinger reduction than the electron-rich one. The anisotropic effect of the double bond in dideoxy neamine (1) will make 2'-N3 more electron deficient, thus, more reactive toward the Staudinger reduction. Fortuitously, by using 4-chlorobenzoyl groups the needed stereoelectronic effect can still be obtained with the N-1 (H-1) being the most reactive (electron deficient) one. Using the above protocol we have been able to introduce the amikacin side chain and have synthesized a novel compound called Pyrankacin with broad spectrum antibacterial activity.
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General Papers: Synthesis of Carbohydrates and Derivatives
1:30 PM-5:10 PM, Wednesday, 29 March 2006 Georgia World Congress Center -- B409, Oral
Division of Carbohydrate Chemistry |
