A Cautionary Tale in Decanolide Synthesis

Abstract

An efficient convergent approach to the synthesis of the novel dioxolenone alcohol 3 is described and on thermolysis of 3 a macrodiolide, 12, was obtained via an intermediate β-acyl ketene. Macrodiolide 16 was obtained on thermolysis of the known dioxolenone alcohol 2 rather than the decanolide, diplodialide A.

Key words

decarestrictines - polyketides - dioxolenones - cyclisation - dimerisation

References and Notes

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12

Macrodiolide 12: [α] _d +40.5 (c 2, CHCl₃); IR (neat): n_max = 1735, 1666, 1633 and 1591 cm^-¹; ^¹H NMR (400 MHz, CDCl₃): δ = 1.34 (6 H, d, J = 6.4 Hz, 2 × CH₃), 2.44 (2 H, dddd, J = 15.0, 7.0, 3.5, 1.0 Hz, 8-HH and 8′-HH), 2.67 (2 H, dddd, J = 15.0, 9.3, 7.8, 1.0 Hz, 8-HH and 8′-HH), 3.54 (2 H, d, J = 15.0 Hz, 2-HH and 2′-HH), 3.60 (2 H, d, J = 15.0 Hz, 2-HH and 2′-HH), 5.10 (2 H, m, 9-H and 9′-H), 5.96 (2 H, m, 7-H and 7′-H), 6.11 (2 H, d, J = 15.5 Hz, 4-H and 4′-H), 6.24 (2 H, t, J = 11.5 Hz, 6-H and 6′-H), 7.45 (2 H, ddd, J = 15.5, 11.5, 1.0 Hz, 5-H and 5′-H); ^¹³C NMR (100 MHz, CDCl₃): δ = 19.8 (2 × CH₃), 34.6 (C-8 and C-8′), 47.6 (C-2 and C-2′), 70.8 (C-9 and C-9′), 129.3 (C-4 and C-4′), 130.1 (C-6 and C-6′), 136.8 (C-7 and C-7′), 138.8 (C-5 and C-5′), 166.9 (C-1 and C-1′) and 191.9 (C-3 and C-3′); MS (CI): m/z = 361.1652 (MH⁺, C₂₀H₂₅O₆ requires 361.1651), 361 (MH⁺, 100%) and 181 (99).

15

Macrodiolide 16: [α] _d + 124 (c 1, CHCl₃); IR (neat): n_max = 1732, 1673, 1627 cm^-¹; ^¹H NMR (400 MHz, CDCl₃): δ = 1.24 (6 H, d, J = 6.4 Hz, 2 × CH₃), 1.40-1.65 (8 H, m, 7-H₂, 7′-H_2, 8-H₂ and 8′-H₂), 2.20 (4 H, m, 6-H₂ and 6′-H₂), 3.52 (2 H, d, J = 14.0 Hz, 2-HH and 2′-HH), 3.57 (2 H, d, J = 14.0 Hz, 2-HH and 2′-HH), 4.97 (2 H, m, 9-H and 9′-H), 6.13 (2 H, dt, J = 16.0, 1.5 Hz, 4-H and 4′-H), 6.86 (2 H, dt, J = 16.0, 6.5 Hz, 5-H and 5′-H); ^¹³C NMR (100 MHz, CDCl₃): δ = 20.0 (2 × CH₃), 23.7 (C-7 and C-7′), 32.2 (C-6 and C-6′), 35.2 (C-8 and C-8′), 47.3 (C-2 and C-2′), 71.5 (C-9 and C-9′), 129.1 (C-4 and C-4′), 148.5 (C-5 and C-5′), 165.8 (C-1 and C-1′) and 190.7 (C-3 and C-3′); MS (EI): m/z = 364.1879 (M⁺, C₂₀H₂₈O₆ requires 364.1886), 364 (M⁺, 5%), 182 (50) and 81 (100).