189748-69-4Relevant articles and documents
A Novel Synthesis of 2′-Modified 2′-Deoxy-4′-thiocytidines from D-Glucose
Yoshimura, Yuichi,Kitano, Kenji,Yamada, Kohei,Satoh, Hiroshi,Watanabe, Mikari,Miura, Shinji,Sakata, Shinji,Sasaki, Takuma,Matsuda, Akira
, p. 3140 - 3152 (2007/10/03)
Novel 2′-deoxycytidine antimetabolites, specifically several 2′-modified 2′-deoxy-4′-thiocytidines, were synthesized as potential new antineoplastic agents. Methyl 3-O-benzylxylofuranoside was converted to a 1,4-anhydro-4-thioarabitol 24. Protection of the primary alcohol of 24 gave a common intermediate (15) which was useful for the synthesis of various 2′-modified 2′-deoxy-4′-thionucleosides. Oxidation of the secondary hydroxyi group of 15, followed by the Wittig reaction or treatment with (diethylamido)sulfur trifluoride (DAST) produced 2-deoxy-2-methylene (26) and 2-deoxy-2,2-difluoro (34) derivatives, respectively. Unique Pummerer-type glycosylation between the corresponding sulfoxides and trimethylsilylated N4-acetylcytosine produced 2′-deoxy-2′-methylene- (10) and 2′-deoxy-2′,2′-difluoro-4′-thiocytidines (11). On the other hand, treatment of 15 with DAST introduced a fluorine atom with retention of the 2′-stereochemistry, yielding 40. In contrast, the Mitsunobu reaction of 3-O-benzoyl derivative 53 which was obtained from 15 in five steps, using diphenylphosphoryl azide gave azide derivative 54 with inverted stereochemistry. These derivatives were converted to the corresponding 1-O-acetyl derivatives via the usual Pummerer rearrangement, which were in turn used to synthesize 4′-thiocytidines 12 and 58. Among the 2′-modified 4′-thiocytidines obtained, 2′-methylene (10) and 2′-fluoro (12) derivatives were found to have potent antineoplastic properties in vitro.
