Total Syntheses of Diospongins A and B

Abstract

The total syntheses of diospongins A and B employing 2,6-disubstituted dihydropyranones as key intermediates are described.

Key words

total synthesis - rearrangement - silicon - epoxide - diospongin

References and Notes

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6

To a well-stirred solution of TBS-dithiane 3 (120 mg, 0.51 mmol) in Et₂O (2 mL), t-BuLi was added (1.7 M in hexane, 0.43 mL) via syringe at -78 ˚C. The reaction mixture was stirred for 1 h at -40 ˚C. Then, a solution of epoxide 5
(1 mmol) in Et₂O (1 mL) was added to the reaction mixture at -78 ˚C. The mixture was allowed to warm to 0 ˚C over
1 h and then recooled to -78 ˚C. A solution of epoxide 4 (1.1 mmol) in Et₂O-HMPA (90 mg HMPA in 1 mL of Et₂O) was added. The reaction mixture was stirred from -78 to 0 ˚C overnight, then quenched with sat. aq NH₄Cl (1 mL). After dilution of the mixture with Et₂O, the organic layer was separated. The aqueous phase was extracted three times with Et₂O, and the combined organic layers were dried over MgSO₄, filtered, and concentrated under reduced pressure. Flash chromatography (hexanes-EtOAc, 30:1) provided
(-)-8 in 74% yield. IR: 3424, 2952, 1255, 1099 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 7.38-7.26 (m, 10 H), 5.12
(d, J = 7.2 Hz, 1 H), 4.53 (d, J = 2.7 Hz, 1 H), 4.52 (s, 2 H), 4.43-4.40 (m, 1 H), 3.63 (t, J = 6.3 Hz, 2 H), 2.79-2.72
(m, 4 H), 2.47-2.36 (m, 4 H), 1.97-1.90 (m, 4 H), 0.92 (s,
9 H), 0.18 (s, 3 H), 0.16 (s, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 145.6, 138.2, 128.3, 128.2, 127.7, 127.5, 126.8, 125.5, 73.2, 70.1, 69.2, 66.8, 51.6, 49.2, 43.6, 38.7, 26.3, 26.1, 25.9, 25.0, 18.1, -3.1, -4.5; [α]^²5 _D -41.5 (c 0.6, CHCl₃). ESI-MS: m/z = 555.9 [M + Na]⁺. HRMS: m/z calcd for calcd for C₂₉H₄₅O₃S₂Si: 533.2579; found: 533.2587 [M + H]⁺.