Undemanding Synthesis of Novel C₁₉ and C₁₇ Analogues of C₁₈-Guggultetrol

Dedicated to the memory of Dr. B. P. Hiwale (Founder of Ahmednagar College).

Abstract

A simple and undemanding synthesis of (2S,3R,4R,5R)-nonadecane-1,2,3,4,5-pentol and (2S,3R)-heptadecane-1,2,3-triol as novel C₁₉ and C₁₇ analogues of C₁₈-guggultetrol was achieved by using l-ascorbic acid as a chiral pool.

Key words

ascorbic acid - chiral pool - guggultetrol - asymmetric synthesis - nonadecanepentol - heptadecanetriol

• References and Notes

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• 13 (2S,3R,4R,5R)-Nonadecane-1,2,3,4,5-pentol (2) Compound 9 (1.4 g, 3.27 mmol) was added to THF (20 mL), and the mixture was cooled to 0 °C. 5% dil aq HCl was added, and the mixture was stirred for 1 h. When the reaction was complete (TLC), the desired compound precipitated out and was collected by filtration then washed with H₂O and 5% EtOAc–hexane to give a white solid; yield: 0.5 g (1.44 mmol, 44%); mp 128–130 °C; [α]_D ²⁵ +20.45 (c 0.4, MeOH). IR (neat): 3433, 3254, 2915, 2848, 1468, 1064, 933, 766, 719 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 4.54 (d, J = 4.4 Hz, 1 H), 4.44 (t, J = 5.7 Hz, 1 H), 4.32 (dd, J = 5.9, 2.6 Hz, 2 H), 4.01 (d, J = 6.6 Hz, 1 H), 3.73–3.70 (m, 1 H), 3.58–3.53 (m, 1 H), 3.51–3.35 (m, 3 H), 3.27–3.21 (m, 1 H), 1.65–1.56 (m, 1 H), 1.51–1.41 (m, 1 H), 1.35–1.03 (br s, 24 H), 0.86 (t, J = 6.8 Hz, 3 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 74.82, 73.76, 70.33, 68.82, 62.51, 33.14, 31.30, 29.40, 29.23, 29.14, 29.12, 29.10, 29.08, 29.02, 28.71, 25.19, 22.08, 13.87. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₉H₄₁O₅: 349.2949; found: 349.2950.
• 14 (2S,3R)-Heptadecane-1,2,3-triol (3) H₅IO₆ (1.04 g, 4.58 mmol) was added to a soln of 9 (1.4 g, 3.27 mmol) in anhydrous THF (20 mL) at 0 °C, and the mixture was stirred for 6 h at r.t. The mixture was neutralized with NaHCO₃ (1.1 g), stirred for 30 min, and filtered through a Celite pad. The filtrate was evaporated to give the crude aldehyde that was used as prepared, without purification, in the next reaction. NaBH₄ (248 mg, 6.54 mmol) was added portionwise to a solution of the aldehyde in MeOH (15 mL), and mixture was stirred for 1 h. When the reaction was complete (TLC), the reaction was quenched with sat. aq NH₄Cl (20 mL), and the mixture was extracted with EtOAc (3 × 10 mL). The combined organic extracts were washed with brine, dried (Na₂SO₄), and concentrated to give a crude alcohol that was used as prepared, without purification, in the next reaction. The crude alcohol was dissolved in THF (7 mL), and the solution was cooled to 0 °C. 5% dil aq HCl was added, and the mixture was stirred for 1 h. When the reaction was complete (TLC), the desired compound precipitated out and was collected by filtration then washed with H₂O and 5% EtOAc–hexane to give a white solid; yield: 0.250 g (0.786 mmol, 24%); mp 110–112 °C; [α]_D ²⁵ +9.32 (c 1.0, MeOH). IR (neat): 3432, 3190, 3000, 2870, 1498, 1080, 903, 888, 719 cm^–1. ¹H NMR (500 MHz, MeOD): δ = 3.73 (dd, J = 11.3, 3.9 Hz, 1 H), 3.60 (dd, J = 11.3, 6.5 Hz, 1 H), 3.56–3.50 (m, 1 H), 3.54–3.46 (m, 1 H), 1.71–1.61 (m, 1 H), 1.60–1.50 (m, 1 H), 1.46–1.23 (br s, 24 H), 0.91 (t, J = 6.9 Hz, 3 H). ¹³C NMR (125 MHz, MeOD): δ = 74.85, 72.54, 63.40, 32.75, 31.57, 29.39, 29.29, 29.27, 29.25, 28.93, 25.35, 22.20, 12.89. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₇H₃₆NaO₃: 311.2562; found: 311.2561.