Nucleosides. IX. The Formation of 2',3'-Unsaturated Pyrimidine Nucleosides via a Novel β-Elimination Reaction^1,2

Properties of 2′,3′‐dideoxy‐2′,3′‐dehydrothymidine 5′‐triphosphate in terminating DNA synthesis catalyzed by several different DNA polymerases

“…dddTTP was synthesized as in [4] with some modifications [5]. DNA polymerase I KF was isolated from E. coli NM 182 as in [6], calf thymus DNA polymerase ce according to [7], rat liver DNA polymerase ~ as described [8], and calf thymus terminal deoxynucleotidyl transferase using the method in [9]; AMV and RSV reverse transcriptases were from Amersham.…”

Synthesis of cyclopentane analogs of 1-(2′,3′-dideoxy-β-glycero-pentofuranosyl)pyrimidine nucleosides

“…Synthesis of (2)-cis-3-aminocyclopentanemethanol (8) The cis configuration of the two substituents in the cyclopentane derivatives shown in Scheme 1 is determined by the starting material, bicyclo[2.2.l]hept-2-ene (I), which, in the first step, is oxidized to cis-l,3-cyclopentanedicarboxylic acid (2) using potassium permanganate by the procedure described by Birch et al (14). The cis-diacid (2) was then converted into (+)-cis-3-aminocyclopentanemethanol (8) by the same series of reactions that was used by O'Dell and Shealy (15) for the preparation of the cyclopentane analogs of 2'-and 3'-deoxyerythro-pentofuranosylamine. The diacid was converted first into the anhydride (3) by heating at reflux temperature in acetic anhydride.…”

“…Compound 23 was coupled with (5)-cis-3-aminocyclopentanemethanol (8) to give compound 27; this product was then cyclized in 15 N aqueous ammonia to give nucleoside analog 31. The corresponding thymine nucleoside analog (32) was prepared as described previously (12).…”

“…10, 3.30, and 3.99. ( f)-3-Ethoxy-N-{N '-[cis -3-(hydro.ryn~ethyl)cyclopentyl]tlziocnrbnmoy1)propennmide (29) 3-Ethoxypropenoyl isothiocyanate (25) was prepared as described previously (20) and used immediately after distillation for the preparation of 29. Compound 25 (1.41 g,8.97 mmol) was added to a solution of 8 (0.934 g, 8.1 1 mmol) in methanol (13 mL) and diethyl ether (20 mL), and the reaction solution was kept at room temperature overnight; the mixture was filtered and the solvent was evaporated. The resulting oil was fractionated by column chromatography on silica gel to give 29 (1.54 g, 70%) as a pale yellow-green oil; R f 0.50 (8:s: 1 (v/v/v) toluene -ethyl acetate -2-propanol).…”

“…In contrast to the relatively large number of 2',3'-dideoxynucleosides that have been synthesized (1)(2)(3)(6)(7)(8), and references therein), there have been described relatively few syntheses of the carbocyclic analogs of the 2',3'-dideoxynucleosides and most of these were of analogs of purine nucleosides. Schaeffer et al (9), in their studies on the structural requirements in inhibitors of the enzyme adenosine deaminase, have synthesized several cis-3-(6-substituted-9-purinyl)cyclopentylmethanols in which the substituent was the C1, SH, OH, NH,, NHCH3, or N(CH3), group.…”