Synthetic studies for functional elucidation of RNA catalysis and H4 receptor

设计并合成了一种新型的C4-咪唑核苷亚磷酰胺。该亚磷酰胺成功地将咪唑部分掺入VS和发夹核酶中。由于修饰后的咪唑核酶既具有切割活性又具有连接活性，因此这些数据为它们的天然核碱基具有一般的酸碱催化作用提供了很好的证据。在此基础上，设计并合成了第二种稳定的咪唑核苷亚磷酰胺类化合物，其2 ′-OH上带有氰乙基作为保护基，并设计并合成了具有两个手性中心和稳定椅型构象的新型组胺H_3拮抗剂。其中，（2S，2 R）-N-烷基衍生物（OUP-153）是一种新的组胺H_3拮抗剂，可使组胺释放增加到基础水平的180-200%。此外，S-烷基-N-烷基异硫脲通过使用3-苯丙酰基异硫氰酸酯（PPI）的合成方法有效地合成。该方法的实用性已通过合成一种有效的H_3拮抗剂氯苄丙酸及其类似物得到证实。

A novel C4-linked imidazole ribonucleoside phosphoramidite was designed and synthesized. This phosphoramidite was successfully incorporated the imidazole moiety into VS and hairpin ribozymes. As the modified imidazole ribozymes thus obtained indicated the activities in both cleavage and ligation, the data provided good evidence for general acid-base catalysis by their natural nucleobases. Further, the second stable imidazole ribonucleoside phosphoramidite has designed and synthesized bearing a cyanoethyl group as a protective group at 2'-OH group.On the other hand, novel histamine H_3 antagonists having two chiral centers and stable chair conformations were designed and synthesized. Among them, a (2S,2R)-N-alkyl derivative (OUP-153), which increased histamine release to 180-200% of basal levels, was found as a novel histamine H_3 antagonist. In addition, S-alkyl-N-alkylisothioureas were efficiently synthesized via a synthetic approach using 3-phenylpropionyl isothiocyanate (PPI). The utility of the approach was proved by the synthesis of clobenpropit, a potent H_3 antagonist and its analogues.