A Convergent and Stereoselective Total Synthesis of Phomolides G and H

Abstract

A stereoselective total synthesis of phomolides G and H, a polyketide natural products is described. The synthesis involves organocatalytic enantioselective asymmetric epoxidation, C1-Wittig olefination, and ring-closing metathesis as key steps. The use of organocatalytic MacMillan asymmetric epoxidation for the construction of two chiral centers of phomolides G and H makes this approach more attractive.

Key words

MacMillan asymmetric epoxidation - ring-closing metathesis - decalactones

• References and Notes

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• 16 Phomolide G (1) [α]_D ²⁵ –6.42 (c 1.0, MeOH). ¹H NMR (300 MHz, CDCl₃ + DMSO-d ₆): δ = 5.72 (dd, 1 H, J = 8.6, 15.8 Hz), 5.18 (dd, 1 H, J = 9.4, 15.8 Hz), 5.09 (s, 1 H), 4.70–4.80 (m, 1 H), 4.58 (s, 1 H), 4.35 (q, 1 H, J = 7.4 Hz), 3.30–3.40 (m, 1 H), 2.58–2.70 (m, 2 H), 2.34 (t, 1 H, J = 10.4 Hz), 1.80–1.90 (m, 2 H), 1.41–1.55 (m, 2 H), 1.23–1.36 (m, 2 H), 0.88 (t, 3 H, J = 7.4 Hz). ¹³C NMR (75 MHz, CDCl₃ + DMSO-d ₆): δ = 169.8, 135.8, 126.8, 77.2, 74.8, 71.9, 70.4, 44.4, 40.1, 38.1, 17.3, 13.0. IR (neat): ν_max = 3356, 2926, 2858, 1743, 1718, 1266, 1198, 776 cm^–1. ESI-HRMS: m/z calcd for C₁₂H₂₀O₅Na: 267.1208; found: 267.1253. Phomolide H (2) [α]²⁰ _D –16.5 (c 1.0, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 5.92 (dd, 1 H, J = 2.8, 15.8 Hz), 5.60 (dd, 1 H, J = 9.1, 15.8 Hz), 4.66 (s, 1 H), 3.75 (t, 1 H, J = 9.3 Hz), 3.35–3.36 (m, 2 H), 3.31 (s, 3 H), 2.57 (dd, 1 H, J = 2.9, 11.8 Hz), 2.47 (dd, 1 H, J = 2.9, 11.8 Hz), 1.83–1.85 (m, 2 H), 1.47–1.35 (m, 2 H), 1.30–1.34 (m, 2 H), 0.91 (t, 3 H, J = 7.5 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 170.1, 135.5, 126.4, 78.8, 75.9, 72.2, 66.6, 48.8, 43.6, 41.1, 38.9, 18.1, 13.1. IR (neat): ν_max = 3356, 2924, 2853, 1734, 1385, 1266, 1163, 1092, 775 cm^–1. ESI-HRMS: m/z calcd for C₁₃H₂₂O₅Na: 281.1365; found: 281.1432.