Total Synthesis of Marine OxylipinsConstanolactone A and B

Abstract

A short, high-yielding synthesis of the marine oxylipins constanolactoneA and B was reported. Starting from cinnamyl alcohol (3), the cylopropyl lactone moiety 2 was obtained in 28% yield (11steps). The second coupling partner, vinyl iodide 1,was isolated in 7 steps and 32% yield. Chromium mediatedaddition yielded the natural products as a 2:1 mixture (74%).

Key words

natural products - total synthesis - asymmetricsynthesis - cyclopropane - ozonolysis

References

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17

Spectroscopic data of the key intermediate 15: [α]_D ²⁰ = 57(c 0.96, CHCl₃). IR(film): ν = 2957(br OH), 2861, 2622, 1729 (C=O), 1718 (C=O) cm^-1.HRMS (CI, 70 eV) for [M + H⁺] (C₉H₁₃O₄):Calcd 185.0755. Found: 185.0808. ¹H NMR (500MHz, CDCl₃): δ = 1.09 (ddd, ³ J = 8.5 Hz, ³ J = 6.8 Hz, ² J _4a,4b = 4.7Hz, 1 H, 4-H_a), 1.29 (ddd, ³ J = 9.4 Hz, ³ J = 4.7 Hz, ² J _4b,4a = 4.6Hz, 1 H, 4-H_b), 1.72 (1 H, dddd, ² J _{5 ′ a,5 ′ b} = 13.8 Hz, ³ J _{5 ′ a,4 ′ a} = 11.7Hz, ³ J _{5 ′ a,6 ′} = 10.6 Hz, ³ J _{5 ′ a,4 ′ b} = 5.0Hz, 5′-H_a), 1.75-1.79 (2 H, m _c , 2-H, 3-H), 1.84 (ddddd, ² J _{4 ′ a,4 ′ b} = 13.0 Hz, ³ J _{4 ′ a,5 ′ a ′} = 11.7 Hz, ³ J _{4 ′ a,3 ′ a} = 9.0 Hz, ³ J _{4 ′ a,3 ′ b} = 7.0Hz, ³ J _{4 ′ a,5 ′ b} = 4.7Hz, 1 H, 4′-H_a), 1.97 (ddddd, ² J _{4 ′ b,4 ′ a} = 13.0 Hz, ³ J _{4 ′ b,3a ′} = 7.1Hz, ³ J _{4 ′ b,3 ′ b} = 5.0Hz, ³ J _{4 ′ b,5 ′ a} = 5.0Hz, ³ J _{4 ′ b,5 ′ b} = 4.7Hz, 1 H, 4′-H_b), 2.05 (1 H, ddddd, ² J _{5 ′ b,5 ′ a} = 13.8Hz, ³ J _{5 ′ b,4 ′ b} = 4.7Hz, ³ J _{5 ′ b,4 ′ a} = 4.7Hz, ³ J _{5 ′ b,6 ′} = 3.3Hz, ⁴ J _{5 ′ b,3 ′ b} = 1.3Hz, 5′-H_b), 2.48 (ddd, ² J _{3 ′ a,3 ′ b} = 17.9 Hz, ³ J _{3 ′ a,4 ′ a} = 9.0Hz, ³ J _{3 ′ a,4 ′ b} = 7.1Hz, 3′-H_a), 2.59 (dddd, ² J _{3 ′ b,3 ′ a} = 17.9 Hz, ³ J _{3 ′ b,4a ′} = 7.0 Hz, ³ J _{3 ′ b,4b ′} = 5.0 Hz, ⁴ J _{3 ′ b,5 ′ b} = 1.3Hz, 1-H, 3′-H_b), 3.91 (1 H, ddd, ³ J _{6 ′ ,5 ′ b} = 10.6 Hz, ³ J _{6 ′ ,3} = 6.7Hz, ³ J _{6 ′ ,5 ′ b} = 3.3Hz, 6′-H), 10.74 (1 H, b, COOH). ¹³CNMR (125 MHz, CDCl₃): δ = 12.1 (C-4),17.8 (C-3), 18.3 (C-4′), 26.6 (C-2), 27.8 (C-5′),29.4 (C-3′), 80.9 (C-6′), 171.4 (C-2′),179.0 (COOH).