P. Peterliroth et al., SYNTHESES OF 6-DEAMINOSINEFUNGIN AND (S)-6-METHYL-G-DEAMINOSINEFUNGIN, Journal of organic chemistry, 59(15), 1994, pp. 4186-4193
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%.