Compounds 9 and 10

in the presence of Cu(II), leaving the 3"-position free for further manipulation. The same combination of transition metals (Cu2+ and Zn2+) was also employed for re-gioselective protection of the amino groups in the syntheses of a series of deaminated derivatives of neamine [24]. When neamine (11) was treated with jV-butoxycarbon-yloxy-5-norbornene-endo-2,3-dicarboxamide (16) in the presence of Zn(II), the di-Boc-protected derivative 12 was obtained, which was subsequently protected at position 3 with jV-benzyloxycarbonyloxy-5-norbornene-e¬ędo-2,3-dicarboxamine (17) (compounds 11-17 ) in the presence of copper(II) to give the neamine derivative 13, having the 2'-amino group free. On the other hand, when initial protection of neamine 11 was performed in the presence of Cu(II), the neamine derivative 14 was formed, which was then converted to compound 15 by further manipulations.

The hindered reagents 16 and 17 have also shown good selectivity for the seemingly unhindered amino groups in the absence of transition metal ions [25,26]. For instance, when neamine 11 was treated with 16 (1 equiv.), 6'-N-protected neam-ine derivative was exclusively formed in 65% isolated yield and 22% of the unreacted neamine was recovered. In a similar manner kanamycin A (4) was selectively protected at the 6'-position to give the monoprotected product in high yield (70%) [26].

Metal-directed protection of amino groups can even be further improved by using a mixture of divalent transition metals. For instance, treatment of kanamycin B (5) with di-ferf-butyldicarbonate in the presence of Zn(II) acetate leads to protection at 3-, 2'-, and 6'-positions (see above), whereas when 5 was subjected to the same reagent in the presence of a mixture of Zn(II) and Cu(II) ions, compound 18 resulted, which is protected only at the 3- and 6'-positions. Subsequent treatment of this intermediate with Zn(II) acetate yielded a complex having the 1- and 3"-amino groups coordinated, allowing selective introduction of the Cbz group at the 2'-position to afford the derivative 19 [27] (compounds 18, 19).

Among transition metal ions employed in regioselective modification of aminoglycosides, Zn2+ and Cu2+ are the most common. They have been used repeatedly


h2nI 11

Cu(OAc)2 17

NH2 16


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