A Carbohydrate-Based Approach for the Total Synthesis of Xyolide

Abstract

We have achieved a total synthesis of xyolide, a bioactive nonenolide, by following a carbohydrate-based approach starting from d-(–)-ribose. The key reactions involved epoxide opening with a long-chain aliphatic Grignard reagent, Yamaguchi esterification, and a ring-closing-metathesis reaction. The longest linear sequence was nine steps and the overall yield was 30%.

Key words

lactones - total synthesis - Grignard reactions - esterification - ring closure - metathesis

• References and Notes


For a review on synthetic, biosynthetic, and pharmacological aspects of decanolides, see:
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• 23 Analytical Data for 10: [α]_D ²⁷ +47.2 (c 0.7, CHCl₃). IR (neat): 3484, 3082, 2956, 2928, 2858, 1737, 1459, 1378, 1166, 1065, 927, 874 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 5.81 (dd, J = 3.3, 15.8 Hz, 1 H), 5.65 (ddd, J = 1.8, 8.7, 15.8 Hz, 1 H), 4.92 (m, 1 H), 4.68 (m, 1 H), 4.16 (m, 1 H), 3.96 (q, J = 4.7, 10.0 Hz, 1 H), 2.34 (m, 1 H), 2.11–2.01 (m, 2 H), 1.78 (m, 1 H), 1.64 (m, 1 H), 1.46 (m, 1 H), 1.54 (s, 3 H), 1.37 (s, 3 H), 1.32–1.20 (m, 10 H), 0.86 (t, J = 6.7 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 175.0, 128.1, 126.2, 109.2, 78.4, 75.5, 75.5, 70.8, 33.5, 31.8, 31.6, 31.1, 29.2, 29.0, 28.3, 26.1, 24.3, 22.5, 13.9. MS (ESI): m/z = 363 [M + Na]⁺.
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• 25 Analytical Data for Xyolide (1): [α]_D ²⁷ +2.6 (c 1.2, CHCl₃). IR (neat): 3613, 3497, 3044, 1744, 1694, 1377, 1059, 968, 772 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 5.86 (dd, J = 1.4, 15.8 Hz, 1 H), 5.49 (ddd, J = 1.7, 9.3, 15.8 Hz, 1 H), 5.14 (m, 1 H), 4.99 (td, J = 2.2, 9.6 Hz, 1 H), 4.50 (br s, J = 1.3, 1.9 Hz, 1 H), 3.56 (dd, J = 1.9, 9.6 Hz, 1 H), 2.67–2.62 (m, 2 H), 2.61–2.51 (m, 2 H), 2.37–2.31 (m, 1 H), 2.09–1.96 (m, 3 H), 1.92–1.83 (m, 1 H), 1.59–1.49 (m, 1 H), 1.33–1.20 (m, 10 H), 0.87 (t, J = 6.7 Hz, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 176.1, 174.5, 171.60, 132.7, 123.4, 76.4, 73.1, 72.4, 70.8, 31.7, 31.4, 31.2, 29.5, 29.4, 29.3, 29.1, 28.8, 24.5, 22.6, 14.0. MS (ESI): m/z = 423 [M + Na]⁺, 399 [M − H]⁺.