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Synlett 2021; 32(07): 689-692
DOI: 10.1055/a-1326-9148
DOI: 10.1055/a-1326-9148
letter
Total Synthesis of (±)-Phaeocaulisin D
Support was provided by the National Institute of General Medical Sciences (1R15GM12068501). A student fellowship was provided by the Iraqi Ministry of High Education and Scientific Research.
Abstract
The tropone sesquiterpene phaeocaulisin D, isolated from the rhizomes of Curcuma phaeocaulis, has previously been shown to inhibit nitric oxide production in macrophages. A total synthesis of phaeocaulisin D was accomplished by using an intramolecular cyclization–dearomatization as a key step. The highlights of the synthesis are effective formation of the 5–7 fused tropone system, and selective methylation of a late-stage intermediate.
Key words
tropones - dearomatization - sesquiterpenes - medicinal chemistry - total synthesis - phaeocaulisinSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1326-9148.
- Supporting Information
Publication History
Received: 12 November 2020
Accepted: 01 December 2020
Accepted Manuscript online:
01 December 2020
Article published online:
05 January 2021
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Phaeocaulisin D (1)
A 3 M solution of MeMgBr in THF (230 μL, 0.68 mmol) was added to a solution of tropone ketone 17 (80 mg, 0.34 mmol) in anhyd THF (3 mL) at –20 °C, and the mixture was warmed to 0 °C and stirred for 2 h. The reaction was quenched by addition of sat. aq NH4Cl (2 mL), and the mixture was diluted with EtOAc (20 mL). The organic layer washed with H2O (5 mL) and brine (5 mL) then dried (Na2SO4). The solvent was evaporated under reduced pressure, and the crude product was purified by chromatography [silica gel, hexane–EtOAc (60:40 to 40:60 over 15 min)] to give a yellow oil; yield: 67.4 mg (79%).
FTIR (film): 2983, 1704, 1603, 1554, 1297, 1146, 1020 cm–1. 1H NMR (400 MHz, CD3OD): δ = 7.90 (s, 1 H), 6.99 (s, 1 H), 2.93 (m, 1 H), 2.81 (m, 1 H), 2.31 (s, 3 H), 2.19 (m, 1 H), 2.06 (m, 1 H), 1.58 (s, 3 H), 1.57 (s, 3 H), 1.43 (s, 3 H). 13C NMR (100 MHz, CD3OD): δ = 188.6, 157.4, 151.8, 148.4, 140.8, 131.6, 84.8, 75.4, 40.1, 32.6, 29.3, 29.0, 27.5, 24.6. HRMS (ESI): m/z [M + H]+ calcd for C15H21O3: 249.1485; found: 249.1463.