Chloroacetaldehyde → Ethenodeoxyadenosine

Participants

Reaction Conditions

Reaction Steps

2′-Deoxyadenosine monohydrate (1) (5.0 g, 20 mmol) was dissolved in 1M aq. sodium acetate buffer (pH 4.5-5.0, 110 mL) by warming to 40-50° C. To the solution chloroacetaldehyde (50% aq. soln, 7.7 mol/L, 25 mL) was added, and the reaction mixture was stirred for 70 h at room temperature. The yellow solution was evaporated to dryness, and the residue was dissolved in MeOH and filtered to remove inorganic salt. After washing with MeOH the combined filtrate and washings were concentrated in vacuo at 40-50° C. The residue was applied to FC (silica gel 60 H, column: 20×6 cm). Elution with CH2Cl2-MeOH (85:15) gave a main fraction from which upon evaporation of the solvent and subsequent crystallization from MeOH-EtOAc compd. 5 (3.86 g, 70%) was isolated as colorless crystals. M.p. 138-141° C. TLC (silica gel, EtOAc-MeOH, 3:1): Rf 0.4. UV (MeOH): λmax 275 (7300), 265 (7600), 258 (6600), 229 nm (35700). 1H-NMR ([D6]DMSO) δ 2.39 (m, 1H, Hα—C(2′)); 2.70 (m, 1H, Hβ—C(2′)); 3.57 (m, 1H, Ha—C(5′)); 3.67 (m, 1H, Hb—C(5′)); 3.88 (m, 1H, H—C(4′); 4.43 (m, 1H, H—C(3′)); 4.99 (t, 1H, 3J(H,H)=5.2 Hz, 5′—OH); 5.38 (d, 1H, 3J(H,H)=3.8 Hz, 3′—OH); 6.47 (pt, 1H, 3J(H,H)=6.2 Hz, H—C(1′)); 7.55 (s, 1H, H—C(11); 8.07 (s, 1H, H—C(10); 8.53 (s, 1H, H—C(2)); 9.29 (s, 1H, H—C(8)).

Provenance & Evidence