Synthetic Studies toward Australifungin

Abstract

As a fungal metabolite, australifungin possesses an α-diketone and a β-ketoaldehyde moiety on its trans-decalin backbone. Microwave-assisted intramolecular Diels–Alder reaction was used as a key strategy to establish the trans-decalin moiety. Further functionalization of the ring B side chain installed the β-ketoaldehyde, one of the two unique functional groups along with the α-diketone.

Key words

Diels–Alder reaction - australifungin - total synthesis - natural product - antifungals - microwave heating

• References and Notes

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• 15 Product 22 A 4 M solution of HCl in 1,4-dioxane (0.2 mL, 0.7751 mmol) was added to a solution of 21 (20 mg, 0.0456 mmol) in THF (5 mL) at 0 °C, and the mixture was warmed to rt and stirred for 2 h. After dilution with H₂O, the mixture was extracted with CH₂Cl₂ and the extracts were washed with sat. aq NaHCO₃. The organic layer was dried (MgSO₄) and filtered through a glass filter. The filtrate was concentrated in vacuo and purified by flash column chromatography (silica gel, 10–15% EtOAc–hexane) to give a colorless oil; yield: 7 mg (39%; 1:1 keto–enol mixture); [α]_D ²⁰ = 34.88 (c = 0.086, CH₂Cl₂). ¹H NMR (500 MHz, CDCl₃): δ = 14.97 (br s, 1 H), 7.91 (s, 1 H), 5.88 (d, J = 10.3 Hz, 1 H), 5.77 (d, J = 4.7 Hz, 1 H), 5.67 (d, J = 10.5 Hz, 1 H), 4.73 (d, J = 6.9 Hz, 1 H), 4.64 (d, J = 6.8 Hz, 1 H), 3.60 (td, J = 9.2, 3.9 Hz, 1 H), 3.38 (s, 3 H), 2.63 (m, 1 H), 2.40 (m, 1 H), 2.26–2.23 (m, 1 H), 1.91 (m, 1 H), 1.57–1.18 (m, 15 H), 1.15 (s, 3 H), 1.01 (m, 1 H), 0.88–0.85 (m, 6 H). ¹³C NMR (500 MHz, CDCl₃): δ = 127.3, 126.7, 100.3, 95.5, 76.7, 55.5, 52.1, 46.0, 41.5, 39.9, 38.6, 32.4, 31.9, 31.1, 29.8, 29.4, 27.1, 25.6, 22.7, 22.0, 17.5, 16.7, 14.1. HRMS (ESI-TOF): m/z [M – H]^– calcd for C₂₄H₄₀O₄: 391.2872; found: 391.2854 (Δ ppm = –4.67).