161258-60-2Relevant academic research and scientific papers
Nucleosides and nucleotides. 151. Conversion of (Z)-2'-(cyanomethylene)-2'-deoxyuridines into their (E)-isomers via addition of thiophenol to the cyanomethylene moiety followed by oxidative syn-elimination reactions
Hassan,Nishizono,Minakawa,Shuto,Matsuda
, p. 6261 - 6267 (1996)
The Wittig reaction of 1-[3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-β-D-erythro-pent ofuranos-2-ulosyl]uracil (6) with Ph3P=CHCN afforded (Z)-2'-cyanomethylene derivative 7 exclusively. The (E)-isomer was accessed from its (Z)-isomer through a sequence of addition of thiophenol to the 2'-cyanomethylene moiety of the (Z)-isomer from the α-face, selectively, and stereoselective oxidative syn-elimination of the resulting adduct. The diastereofacial selectivity of the benzenethiolate addition to the cyanomethylene moiety was found to be influenced by participation of the 2-carbonyl group at the base moiety and steric hindrance of the sugar protecting groups. Although nucleophilic addition reactions at the 2'-position of 6 have been well-known to occur from the α-face selectively, treatment of 7 with LiSPh in THF unexpectedly afforded a mixture of α- and β-phenylthio derivatives 8 and 9 in almost equal ratio. Furthermore, an unusual β-facial selective addition was observed on treatments of 7 with PhSAlMe2 in CH2Cl2 or with LiSPh in the presence of Mg(ClO4)2 in THF. On the other hand, when (Z)-2'-(cyanomethylene)-5'-O-triisopropylsilyl derivative 10 was treated with LiSPh, the α-phenylthio derivative 13 was obtained predominantly (89:11). Oxidation of 8 with m-chloroperbenzoic acid (m-CPBA) in CH2Cl2 and pyrolysis of the resulting sulfoxides afforded the (Z)-isomer 7 exclusively. Treatment of 13 with m-CPBA under the same conditions afforded the desired (E)-cyanomethylene derivatives 18 as a major product (E:Z = 14:1) in good yield. Deprotection of 18 by the standard procedures furnished (E)-2'-(cyanomethylene)-2'deoxyuridine (5).
