260409-23-2Relevant articles and documents
Enantiomeric Syntheses of Conformationally Restricted D- and L-2′,3′-Dideoxy-2′,3′-endo-methylene Nucleosides from Carbohydrate Chiral Templates
Chun, Byoung K.,Olgen, Sureyya,Hong, Joon H.,Newton, M. Gary,Chu, Chung K.
, p. 685 - 693 (2000)
D- and L-2′,3′-dideoxy-2′,3′-endo-methylene nucleosides were synthesized as potential antiviral agents. The key intermediates 5-O-tert-butyldiphenylsilyl-D- and L-2,3-dideoxy-2,3-endo-methylenepentofuranoses (20 and 33, respectively) were obtained by selective protection of the D- and L-2,3-dideoxy-2,3-endo-methylenepentose derivatives 19 and 32 which were prepared from 1,2:5,6-di-O-isopropylidene-D-mannitol and L-gulonic γ-lactone, respectively, and converted to 5-O-tert-butyldiphenylsilyl-D- and L-2,3-dideoxy-2,3-endo-methylenepentofuranosyl acetates (21 and 34, respectively) or the chlorides 22 and 35. The acetates and chlorides were condensed with pyrimidine and purine bases by Vorbrueggen conditions or SN2-type condensation. Vorbrueggen conditions using the acetates gave mostly α-isomers. In contrast, SN2-type condensation using the chlorides greatly improved the β/α ratio. From the synthesis, several D- and L-2′,3′-dideoxy-2′,3′-endo-methylene nucleoside analogues have been obtained, and their structures have been elucidated by NMR spectroscopy and X-ray crystallography. The synthesized D- and L-adenine derivatives were tested as substrates of adenosine deaminase, which indicated that the D-adenosine derivative 4a was a good substrate of a mammalian adenosine deaminase from calf intestinal mucosa (EC 3.5.4.4) while its L-enantiomer 10a was a poor substrate. Either the D-adenine derivative 4a or its L-enantiomer 10a did not serve as an inhibitor of the enzyme.
