SYNTHESES OF 6-DEAMINOSINEFUNGIN AND (S)-6-METHYL-G-DEAMINOSINEFUNGIN

The nucleosides S-adenosylmethonine (SAM, AdoMet) and S-adenosylhomocy steine (SAH, AdoHcy) are involved in a number of important enzyme syst ems. The direct or indirect inhibition of these enzymes is currently o f high interest, particularly in the areas of antiviral and cell proli feration research. We report here the first chirospecific syntheses of G(S)-methyl-6-deaminosinefungin (4) and 6-deaminosinefungin (5) which are analogues of SAM (1), SAH (2), and sinefungin (3). From ketone 6 (tert-butyl [methyl fonyl)amino]-beta-D-ribo-deculofuranosid]uronate), an intermediate in the sinefungin synthesis, the methylene derivative was prepared by using the tosylhydrazone-hydroboration method. Nucleo side formation with adenine and deprotection then led to 6-deaminosine fungin. For the synthesis of (S)-6-methyl-6-deaminosinefungin (4), ket one 6 was converted in four steps into the 6(S)-methyl derivative usin g a cuprate reagent. After the adenine was attached, an appropriate de protection sequence yielded 4. Thus, 4 was synthesized in 11 steps fro m ketone 6 in an overall yield of 13%.