Poon Kevin W C, Datta Apurba
Department of Medicinal Chemistry, The University of Kansas, Lawrence, Kansas 66045-7582, USA.
Nucleosides Nucleotides Nucleic Acids. 2008 Aug;27(8):914-30. doi: 10.1080/15257770802257820.
A concise synthetic route to a novel class of conformationally rigid 3',4'-cis-fused bicyclic nucleoside derivatives has been developed. The synthetic strategy and approach involves initial synthesis of a key [5,5]-bicyclic 6-aminofurofuran-2-one scaffold, employing an L-serine derived aminobutenolide as a strategically functionalized chiral template. Subsequent utilization of the carbonyl functionality of the above bicyclic lactone toward nucleobase incorporation, and linking of the resident amine functionality with appropriately protected amino acids completed the syntheses of the target bicyclic nucleoside-amino acid conjugates. Following the above route, and utilizing a combination of easily available nucleobases (4) and amino acids (4) as the two diversity elements, combinatorial synthesis of a 16-member demonstration library of the title amino acid-linked nucleosides has been accomplished.
已开发出一种简洁的合成路线，用于制备一类新型的构象刚性3'，4'-顺式稠合双环核苷衍生物。该合成策略和方法包括首先合成关键的[5,5]双环6-氨基呋咱并呋喃-2-酮骨架，采用L-丝氨酸衍生的氨基丁烯内酯作为具有战略功能化的手性模板。随后利用上述双环内酯的羰基官能团引入核苷碱基，并将残留的胺官能团与适当保护的氨基酸连接，完成了目标双环核苷-氨基酸缀合物的合成。按照上述路线，并利用易于获得的核苷碱基（4种）和氨基酸（4种）作为两种多样性元素，完成了标题中氨基酸连接核苷的16元示范库的组合合成。
