Concise Synthesis of (1R,2S,3R,6R)-6-Ethoxy-4-(hydroxymethyl)cyclohex-4-ene-1,2,3-triol, a Key Intermediate for the Synthesis of Uvacalols I and J

Abstract

Uvacalols are novel carbasugars isolated from the genera Uvaria. In this study, we report concise syntheses of (1R,2S,3R,6R)-6-ethoxy-4-(hydroxymethyl)cyclohex-4-ene-1,2,3-triol, a key intermediate for the synthesis of uvacalols I and J, and of its epimer (1R,2S,3S,6R)-6-ethoxy-4-(hydroxymethyl)cyclohex-4-ene-1,2,3-triol, starting from cheap and readily available methyl d-glucopyranoside.

Keywords

uvacalols - carbasugars - methyl glucopyranoside - asymmetric synthesis

• References and Notes

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• 21 (1R,2S,3R,6R)-6-Ethoxy-4-(hydroxymethyl)cyclohex-4-ene-1,2,3-triol (16)¹³ Anhyd FeCl₃ (0.036 g, 0.22 mmol) was added to a solution of 24 (0.070 g, 0.14 mmol) in anhyd CH₂Cl₂ (5 mL) at rt, and the resulting mixture was stirred at rt for 3 h until the reaction was complete (TLC). The solvent was evaporated under reduced pressure and the residue was purified by column chromatography [silica gel, EtOAc–MeOH (9:1)] to give a colorless syrup; yield: 0.027 g (75%); [α]_D ²³ –3.3 (c = 0.5, MeOH).IR (neat): 3356, 1674, 1438, 1199, 1142, 771, 723 cm^–1. ¹H NMR (400 MHz, CD₃OD): δ = 5.58 (s, 1 H), 4.11–3.96 (m, 3 H), 3.76 (s, 1 H), 3.66–3.52 (m, 2 H), 3.34–3.22 (m, 2 H,), 1.13 (t, J = 0.9 Hz, 3 H). ¹³C NMR (100 MHz, CD₃OD): δ = 141.36, 122.87, 81.31, 77.71, 75.78, 73.81, 66.27, 62.73, 15.90. MS (ESI): m/z = 227 [M + Na]⁺. HRMS (ESI): m/z [M + Na]⁺ calcd for C₉H₁₆NaO₅: 227.0895; found: 227.0893.
• 22 (1R,2S,3S,6R)-6-Ethoxy-4-(hydroxymethyl)cyclohex-4-ene-1,2,3-triol (17)Prepared from compound 25 by using a similar procedure to the above to give a syrup; yield: 0.081 g (74%); [α]_D ²³ +1.2 (c = 1.0, MeOH).IR (neat): 3332, 1641, 1433, 1201, 1014, 771 cm^–1. ¹H NMR (400 MHz, CD₃OD): δ = 5.77 (s, 1 H), 4.20–4.06 (m, 3 H), 3.60–3.56 (m, 3 H), 3.36 (s, 2 H,), 1.21 (t, J = 6.9 Hz, 3 H). ¹³C NMR (125 MHz, CD₃OD): δ = 140.69, 125.38, 81.59, 72.87, 72.45, 68.15, 65.97, 63.77, 15.92. MS (ESI): m/z = 227 [M + Na]⁺. HRMS (ESI): m/z [M + Na]⁺ calcd for C₉H₁₆NaO₅: 227.0895; found: 227.0889.