Concise Diastereoselective Total Synthesis of (±)-Parvistemonine A

Abstract

We have developed a concise diastereoselective total synthesis of (±)-parvistemonine A. By using a Mukaiyama–Michael addition, an aza-Wittig reaction, a Paal–Knorr pyrrole synthesis, an acid-mediated annulation, and a Mitsunobu reaction as key steps, we achieved a total synthesis in which the longest linear sequence was ten steps and the overall yield was 19.6%. Additionally, the relative stereochemistry of parvistemonine A was confirmed by X-ray crystallographic analysis for the first time.

Key words

parvistemonine A - natural product - total synthesis - aza-Wittig reaction - Mitsunobu reaction

Publikationsverlauf

Eingereicht: 04. August 2020

Angenommen nach Revision: 20. August 2020

Artikel online veröffentlicht:
18. September 2020

• References and Notes

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• 19 (±)-Parvistemonine A [(±)-1)]A 1 M solution of NaOH in MeOH (527 µL) was added to a stirred solution of lactone 19 (13.8 mg, 52.7 µmol) in THF (5.3 mL) at 25 °C, and the mixture was stirred for 1 h at 25 °C. The pH of the reaction mixture was adjusted to 4–5 by addition of 1 M aq HCl, and the resulting mixture was diluted with EtOAc/H₂O and extracted with EtOAc (×6). The combined organic layer was dried (Na₂SO₄), filtered, and concentrated. The residue was treated at 25 °C with a second reaction mixture separately prepared in advance from bis(2-methoxyethyl) azodicarboxylate (185 mg, 791 µmol) and PPh₃ (207 mg, 791 µmol). The resulting mixture was stirred for 1 h at 25 °C, and the reaction was then quenched by addition of sat. aq NaHCO₃. The mixture was diluted with EtOAc/H₂O and extracted with EtOAc (×3). The combined organic layer was dried (Na₂SO₄), filtered, and concentrated. The residue was purified by flash column chromatography [silica gel, hexane–Et₂O (100:0 to 3:1)] to give a colorless oil; yield: 10.6 mg (40.6 µmol, 77%).¹H NMR (600 MHz, CDCl₃): d = 5.85 (d, J = 3.6 Hz, 1 H), 5.82 (d, J = 3.6 Hz, 1 H), 4.19 (dd, J = 14.4, 5.4 Hz, 1 H), 3.89 (ddd, J = 11.4, 9.6, 3.6 Hz, 1 H), 3.63 (dd, J = 14.4, 11.4 Hz, 1 H), 3.03–2.93 (m, 2 H), 2.57–2.48 (m, 3 H), 2.14–2.10 (m, 1 H), 1.80–1.73 (m, 1 H), 1.61–1.54 (m, 3 H), 1.45–1.37 (m, 5 H), 0.94 (t, J = 7.2 Hz, 3 H). ¹³C NMR (151 MHz, CDCl₃): d = 178.44, 134.27, 128.06, 104.32, 102.98, 81.75, 49.42, 44.12, 39.41, 34.34, 31.53, 26.30, 25.98, 22.51, 13.90, 13.83. HRMS (ESI) m/z [M + Na]⁺calcd for C₁₆H₂₃NNaO₂: 284.1621; found: 284.1646.