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For the chemical installation of AHB at the N-1 position of NB30, we choose an approach that utilizes direct regioselective differentiation of the aminoglycoside amino groups by metal-mediated chelation[19] as illustrated in Scheme 2. Treatment of paromamine with Zn(OAc)2 and Boc2O afforded the selectively N-1-Boc-protected paromamine (32% isolated yield, which after azidation (TfN3) and regioselective acetylation (Ac2O at low temperature) gave the acceptor 17. Glycosidation of 17 with the trichloroacetimidiate donor under Lewis acid conditions furnished the desired pseudotrisaccharide 18. Compound 18 was then subjected to a sequential two-step procedure for the installation of the AHB moiety: treatment with TFA to remove the Boc group and the reaction of the resulted N-1 amine with (S)-2-hydroxy-4-azidobutyric acid (HOBT, DCC, Et3N) afforded the acyl migration product from the
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3N) afforded the acyl migration product from the 6 position to N-1 amine as a main product (75%). To avoid this limitation, 17 was first converted to the corresponding 6-hydroxy compound 19 in two successive steps (78%), which after the same two steps for the installation of AHB followed by treatment with methylamine and the Staudinger reaction furnished the desired product NB54 bearing the AHB moiety at the N-1 position.
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