Synthesis of 5'-hydroxyalkyl-5'-deoxy-8,5'(R and S)-cycloadenosines. Nucleosides and nucleotides. XXXI.
作者:AKIRA MATSUDA、KAORI NIIZUMA、TOHRU UEDA
DOI:10.1248/cpb.28.876
日期:——
Treatment of 2', 3'-O-isopropylidene-5'-oxo-8, 5'-cycloadenosine with dimethyloxosulfonium methylide followed by hydrogenation afforded the diastereomeric pairs of 5'-methyl-5'-deoxy-8, 5'-cycloadenosine and 5'-hydroxymethyl-5'-deoxy-8, 5'-cycloadenosine. The configurations at the 5'-positions of these 8, 5'-cycloadenosines were determined by nuclear magnetic resonance (NMR) measurements. The Wittig reactions of the 5'-oxo-8, 5'-cycloadenosine with methoxymethylenetriphenylphosphorane, methylthiomethylenetriphenylphosphorane, and ethyl (dimethylsulfuranylidene) acetate afforded the corresponding 5'-substituted derivatives. The action of ethoxycarbonylmethylenetriphenylphosphorane with the 5'-oxo-8, 5'-cycloadenosine afforded the 5'-ethoxycarbonylmethylene-8, 5'-cycloadenosine, which was converted to 5'-hydroxyethyl-5'-deoxy-8, 5'-cycloadenosine by reduction with LiBH4 followed by deacetonation. The 5'(R)- and 5'(S)-diastereomers of the 5'-hydroxyethyl derivative were separated and identified by NMR analysis. The circular dichroism (CD) spectra of the 5'-substituted-8, 5'-cycloadenosines showed that the diastereomers having the substituent at the trans-gauche position around the C4'-C5' bond gave strong negative CD bonds, whereas the diastereomers with the 5'-substitutent at the gauche-trans position exhibited positive bands.
用二甲基氧锍甲基化物处理 2', 3'-O-异亚丙基-5'-氧代-8, 5'-环腺苷,然后氢化,得到 5'-甲基-5'-脱氧-8, 5'-环腺苷的非对映体对和5'-羟甲基-5'-脱氧-8,5'-环腺苷。这些8, 5'-环腺苷的5'位构型通过核磁共振(NMR)测量确定。 5'-氧代-8, 5'-环腺苷与甲氧基亚甲基三苯基正膦、甲硫基亚甲基三苯基正膦和(二甲基亚磺酰基)乙酯的维蒂希反应得到相应的5'-取代的衍生物。乙氧基羰基亚甲基三苯基正膦与5'-氧代-8, 5'-环腺苷反应得到5'-乙氧基羰基亚甲基-8, 5'-环腺苷,将其转化为5'-羟乙基-5'-脱氧-8, 5'-通过用 LiBH4 还原然后脱丙酮来生成环腺苷。通过NMR分析分离并鉴定5'-羟乙基衍生物的5'(R)-和5'(S)-非对映体。 5'-取代的 8, 5'-环腺苷的圆二色性 (CD) 光谱表明,在 C4'-C5' 键周围的反式高斯位置具有取代基的非对映体产生强负 CD 键,而非对映体则具有强负 CD 键。 5'-取代基位于gauche-trans位置时表现出阳性条带。