Michel Benoît Y, Strazewski Peter
UMR 5246, CNRS, Laboratoire de Synthèse de Biomolécules, Université Claude Bernard Lyon 1, Villeurbanne, Université de Lyon, 69622 Lyon, France.
Chemistry. 2009 Jun 15;15(25):6244-57. doi: 10.1002/chem.200802629.
An original synthetic approach for the first synthesis of an enantiopure methanocarba puromycin (3'-alpha-aminoacylamino-3'-deoxyadenosine) analogue and its cytidine dinucleotide derivative is described. Each compound is conformationally locked in a North-type pucker and exhibits both a pseudoaxial hydroxy group and a pseudoequatorial aminoacyl group. The syntheses were accomplished from D-ribose in 18 and 19 steps, respectively, with key steps being a ring-closing metathesis, a Luche reduction, a Simmons-Smith cyclopropanation, a Mitsunobu coupling, a Mattocks bromoacetylation, a regioselective and a stereoselective nucleophilic substitution, a chemoselective phosphoramidite coupling and a Staudinger-Vilarrasa coupling. Both molecules are being tested for peptidyl transfer efficiency in ribosomes for comparison with the peptidyl transfer kinetics of natural puromycin and other natural and synthetic ribosomal A site substrates.
描述了一种首次合成对映体纯的甲碳环嘌呤霉素（3'-α-氨酰基氨基-3'-脱氧腺苷）类似物及其胞苷二核苷酸衍生物的原创合成方法。每种化合物在构象上被锁定为北型褶皱，并且同时具有一个假轴向羟基和一个假赤道氨酰基。合成分别从D-核糖经18步和19步完成，关键步骤包括闭环复分解反应、吕克还原反应、西蒙斯-史密斯环丙烷化反应、光延反应、马托克斯溴乙酰化反应、区域选择性和立体选择性亲核取代反应、化学选择性亚磷酰胺偶联反应以及施陶丁格-比利亚拉萨偶联反应。正在对这两种分子进行核糖体中肽基转移效率的测试，以便与天然嘌呤霉素以及其他天然和合成核糖体A位点底物的肽基转移动力学进行比较。
