THE TOTAL SYNTHESIS OF ALCALIGIN

The first total synthesis of 1,8(S),11,18(S)-tetrahydroxy-1,6,11,16-tetraazaacycloeicosane-2,5,12,15-tetrone (alcaligin) is presented. The key step involves the coupling of O-benzyl-N-(tert-butoxycarbonyl)hydroxylamine to 2(S)-(benzyloxy)-1,4-bis(tosyloxy)butane (2). The resulting monotosylate 3 was then converted to the primary amine 5, which was subjected to a series of selective acylations and N-deprotections to produce the linear omega-amino acid 11. The omega-amino acid was next cyclized to the 20-membered ring, tetrabenzylalcaligin (12). Finally, deprotection of the hydroxamates and alcohols in the last step afforded the chiral natural product, alcaligin (1).