A Simple and Efficient Synthesis of 2-Deoxy-l-ribose from 2-Deoxy-d-ribose

Abstract

An efficient synthesis of 2-deoxy-l-ribose was achieved without chromatography starting from its enantiomer 2-deoxy-d-ribose in more than 30% overall yield. An unexpected product, 2-deoxy-xylose, was obtained under slightly different reaction conditions and isolated with partial racemization. The structure of the scalemic 2-deoxy-xylose was confirmed by X-ray crystallography.

synthesis - deoxyribose - enantiomer

References and Notes

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<A NAME="RW10106ST-8">8</A>

Typical procedure for 2-deoxy-xylose: To a solution of 4 (10 g, 0.022 mol) in DMF (30 mL) was added potassium benzoate (30 g, 0.19 mol), and the mixture was heated at reflux with stirring for 10 h. The resulting mixture was concentrated and stirred with H₂O (50 mL) and CH₂Cl₂ (30 mL), filtered, and the aqueous layer of the filtrate was separated and extracted with CH₂Cl₂ (30 mL). The combined organic layers were evaporated to dryness and the residue recrystallized from EtOH-H₂O to give 7 as white crystals (3.9 g, 50%). This material was dissolved in MeOH (60 mL), the solution was saturated with NH₃, and stirred at r.t. for 24 h. After evaporation, the residual syrup was partitioned between H₂O (70 mL) and CH₂Cl₂ (70 mL), and the aqueous layer was separated and washed again with CH₂Cl₂ (50 mL). The resulting aqueous solution was saturated with benzoic acid and heated at reflux for 1 h. After cooling to r.t., CHCl₃ (25 mL) was added, and the aqueous layer separated and washed again with CHCl₃ (25 mL). The aqueous layer was concentrated to dryness and recrystallized from acetone-EtOAc (1:1) to give 2-deoxy-xylose (9) as white crystals (1.6 g, 83%). Single crystals suitable for X-ray diffraction measurements were obtained from acetone-EtOAc by slow evaporation at r.t. Analytical data: mp 77-78 °C; [α]²⁰ _D +0.6 (c 1.00, H₂O); ¹H NMR (300 MHz, DMSO-d ₆): δ = 6.47 (d, J = 6.6 Hz, 1 H), 4.84 (dd, J ₁ = 4.6 Hz, J ₂ = 4.8 Hz, 2 H), 4.59-4.53 (m, 1 H), 3.68-3.62 (dd, J ₁ = J ₂ = 5.0 Hz, 1 H), 3.33-3.27 (m, 1 H), 3.19-3.10 (m, 1 H), 2.98-2.91 (m, 1H), 1.93-1.87 (dddd, J ₁ = J ₂ = J ₃ = J ₄ = 2.0 Hz, 1 H), 1.31-1.20 (m, 1 H); ESI-MS: m/z = 179 [M + HCOO^-]; Anal. Calcd for C₅H₁₀O₄: C, 44.77; H, 7.52. Found: C, 45.02; H, 7.33.

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<A NAME="RW10106ST-10">10</A>

CCDC 293775 contains the supplementary crystallographic data and collection parameters for 9. These data can be obtained free of charge via ww.ccdc.cam.ac.uk/conts/retrieving.html.

<A NAME="RW10106ST-11">11</A>

Typical procedure for 2-deoxy-l-ribose: To a solution of 4 (10 g, 0.022 mol) in DMF (30 mL) was added H₂O (5 mL) and potassium benzoate (25 g, 0.16 mol), and the mixture was heated at reflux with stirring for 6 h. The resulting mixture was concentrated and stirred with H₂O (50 mL) and CH₂Cl₂ (30 mL), filtered, and the aqueous layer of the filtrate was separated and extracted with CH₂Cl₂ (30 mL). The organic layers were combined and treated with Na₂CO₃ and evaporated to a syrup (mixture 10). This material was dissolved in MeOH (60 mL), the solution saturated with NH₃, and stirred at r.t. for 24 h. After evaporation, the residual syrup was partitioned between H₂O (20 mL) and CH₂Cl₂ (20 mL), and the aqueous layer was separated and washed again with CH₂Cl₂ (20 mL) before being evaporated to dryness and the residue recrystallized from Et₂O to give mixture 11 as a white solid (1.9 g, 46%). The solid was heated at reflux in a saturated aqueous solution of benzoic acid (80 mL) for 1 h. After cooling to r.t., CHCl₃ (30 mL) was added, and the aqueous layer separated and washed again with CHCl₃ (20 mL) before being concentrated to give a colorless syrup. The syrup was treated with a small amount of acetone-isopropanol (7:1) and refrigerated for about a week to give 2-deoxy-l-ribose (12) as a white powder (1.6 g, 95%). Data: mp 74-76 °C; [α]²⁰ _D +53 (c 1.00, H₂O); ¹H NMR (300 MHz, D₂O): δ = 5.47-5.13 (m, 1 H), 4.22-3.42 (m, 4 H), 2.29-1.50 (m, 2 H); ESI-MS: m/z = 179 [M+HCOO^-] (weak); Anal. Calcd for C₅H₁₀O₄: C, 44.77; H, 7.52. Found: C, 44.61; H, 7.75.