A Practical and Scalable Preparation of Lusianthridin

Abstract

The efficient preparation of the stilbenoid lusianthridin is described. This synthesis relies on a Suzuki–Miyaura coupling and an intramolecular nucleophilic substitution as key reactions to construct the 9,10-dihydrophenanthrene core. The synthesis is completed in seven steps with a 13.2% overall yield, and each step can be conducted on a >20 gram scale. The route has provided 20 grams of lusianthridin for further biological activity studies.

Key words

lusianthridin - dihydrophenanthrene - Suzuki–Miyaura reaction - intramolecular nucleophilic substitution - large-scale preparation of stilbenoids

Publication History

Received: 18 March 2022

Accepted after revision: 18 April 2022

Accepted Manuscript online:
18 April 2022

Article published online:
05 May 2022

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• 24 Lusianthridin (1)^6b After two vacuum/N₂ cycles to replace air inside the reaction tube, a mixture of compound 20 (118.0 mmol, 1.0 equiv) and 10% Pd/C (5.0 g) in MeOH (50 mL) was vigorously stirred at r.t. under 1 atm of H₂ for 12 h. Upon full consumption of 20, the mixture was filtered through Celite, and the filtrate was concentrated in vacuo and redissolved in CH₂Cl₂. The solution was stirred and mixed with hexane to afford a white precipitate that was collected by filtration to give a white solid; yield: 20 g (73%). ¹H NMR (600 MHz, CD₃OD): δ = 8.19–8.11 (m, 1 H), 6.66–6.56 (m, 2 H), 6.33 (s, 2 H), 3.75 (s, 3 H), 2.74–2.60 (m, 4 H). ¹³C NMR (150 MHz, CD₃OD): δ = 159.8, 156.4, 156.0, 141.8, 140.3, 130.1, 126.5, 116.2, 115.0, 113.6, 106.0, 101.4, 55.5, 31.9, 31.2. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₅H₁₅O₃: 243.1016; found: 243.1017.