Enantioselective Stereodivergent Synthesis of Jaspine B and 4-epi-Jaspine B from Axially Chiral Allenols

Abstract

A short enantioselective synthetic route to the cytotoxic marine natural product jaspine B has been developed. A chiral non-racemic primary α-allenol, obtained from pentadecanal, gave access to an enantioenriched 2-tetradecyl-2,5-dihydrofuran as key intermediate. A stereodivergent functionalization of this dihydrofuran allowed access in a few steps to jaspine B and its 4-epimer.

Key words

jaspine B - pachastrissamine - allenol - enatioselective allenylation - epoxydation

• References and Notes

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• 17 (1S,2S,5R)-2-Tetradecyl-3,6-dioxabicyclo[3.1.0]hexane (trans-6) and (1R,2S,5S)-2-tetradecyl-3,6-dioxabicyclo[3.1.0]hexane (cis-6): Trifluoroacetic acid (1.29 mL, 9 mmol) was added slowly to a solution of (S)-2-tetradecyl-2,5-dihydrofuran (400 mg, 1.50 mmol) and urea-hydrogen peroxide complex (2.8 g, 22.5 mmol) in CH₂Cl₂ (20 mL). After 15 min stirring at r.t., the reaction mixture was diluted with an aqueous solution of Na₂SO₃ (1 M, 15 mL) and extracted with CH₂Cl₂ (3 × 20 mL). The organic phases were collected, dried over magnesium sulfate, and concentrated to dryness to give a residue, which was purified by flash chromatography on neutral alumina (EtOAc/petroleum ether 2:98) to give the epoxide trans-6 (188 mg, 44%) and epoxide cis-6 (149 mg, 35%). trans-6: ¹H NMR (CDCl₃, 300 MHz): δ = 4.1–4.0 (m, 1 H, H2), 3.97 (d, J = 10.6 Hz, 1 H, H5a), 3.75 (dd, J = 3.0, 0.7 Hz, 1 H, H4), 3.70 (d, J = 10.6 Hz, 1 H, H5b), 3.58 (d, J = 3.0 Hz, 1 H, H3), 1.5–1.35 (m, 2 H, H1′), 1.35–1.2 (m, 24 H, H2′–H13′), 0.95–0.8 (m, 3 H, H14′). ¹³C NMR (CDCl₃, 75 MHz): δ = 77.8 (C2), 66.1 (C5), 59.1 (C3), 56.0 (C4), 32.1, 31.1, 29.8, 29.7, 29.6, 29.5, 25.6, 22.8 (C1′–C13′), 14.3 (C14′). HRMS: m/z [M+H]⁺ calcd for C₁₈H₃₅O₂: 283.2637; found: 283.2645. [α]_D ²⁵= –11.8 (c 1.23, CHCl₃). cis-6: ¹H NMR (CDCl₃, 300 MHz): δ = 4.04 (d, J = 10.6 Hz, 1 H, H5a); 3.76 (t, J = 6.7 Hz, 1 H, H2), 3.72 (dd, J = 3.1, 0.5 Hz, 1 H, H4), 3.66 (dd, J = 10.6, 0.6 Hz, 1 H, H5b), 3.64 (d, J = 3.2 Hz, 1 H, H3), 1.75–1.6 (m, 2 H, H1′), 1.5–1.2 (m, 24 H, H2′–H13′), 0.95–0.8 (m, 3 H, H14′). ¹³C NMR (CDCl₃, 75 MHz): δ = 77.8 (C2), 67.6 (C5), 57.6 (C3), 56.0 (C4), 32.1, 31.1, 30.3, 29.8, 29.7, 29.5, 26.3, 22.8 (C1′–C13′), 14.3 (C14′). HRMS: m/z [M+H]⁺ calcd for C₁₈H₃₅O₂: 283.2637; found: 283.2624. [α]_D ²⁵= +17.6 (c 1.48, CHCl₃).
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• 19 All analyses were in agreement with the data reported in the literature (ref. 3f). [α]_D ²⁵ = +18.1 (c 0.80, EtOH). Lit. (ref. 3f) [α]_D ²⁵ = +18.8 (c 0.85, EtOH).
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• 21 All analyses were in agreement with the data reported in the literature (ref. 3h). [α]_D ²⁵ = –7.1 (c 0.46, MeOH). Lit. (ref. 3h) [α]_D ²⁵= –7.3 (c 0.46, MeOH).