Syntheses of 6-deaminosinefungin and (S)-6-methyl-6-deaminosinefungin

Article abstract of DOI:10.1021/jo00094a033

The nucleosides S-adenosylmethionine (SAM, AdoMet) and S-adenosylhomocysteine (SAH, AdoHcy) are involved in a number of important enzyme systems. The direct or indirect inhibition of these enzymes is currently of high interest, particularly in the areas of antiviral and cell proliferation research. We report here the first chirospecific syntheses of 6(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 2,3-O-isopropylidene-5,7,8,9-tetradeoxy-9(S)-[(p-toluenesulfonyl)amino -β-D-ribo-deculofuranosid]uronate), an intermediate in the sinefungin synthesis, the methylene derivative was prepared by using the tosylhydrazone-hydroboration method. Nucleoside formation with adenine and deprotection then led to 6-deaminosine fungin. For the synthesis of (S)-6-methyl-6-deaminosinefungin (4), ketone 6 was converted in four steps into the 6(S)-methyl derivative using a cuprate reagent. After the adenine was attached, an appropriate deprotection sequence yielded 4. Thus, 4 was synthesized in 11 stops from ketone 6 in an overall yield of 13%.