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DOI: 10.1055/a-1967-1284
Total Synthesis and Structural Revision of Cephalosporolide J
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Abstract
Herein, we report the first total synthesis of cephalosporolide J, which is a deep sea sediment derived polyketide harboring a unique bicyclo[3.3.0]furanolactone moiety. The adopted synthetic strategy consisted of the alkynylation of γ-lactone with lithium alkynyltrifluoroborate followed by a spiroketalization triggered by hydrogenation of the triple bond. Through this synthesis, the correct structure of cephalosporolide J is shown to be that of the 9-epi stereoisomer of the structure originally proposed.
Key words
cephalosporolide J - polyketide - bicyclo[3.3.0]furanolactone - total synthesis - structural revisionSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1967-1284.
- Supporting Information
Publikationsverlauf
Eingereicht: 06. Oktober 2022
Angenommen nach Revision: 24. Oktober 2022
Accepted Manuscript online:
24. Oktober 2022
Artikel online veröffentlicht:
23. November 2022
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References and Notes
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- 21 Procedure for the Synthesis of α,β-Unsaturated Ynone 8 BuLi (2.40 mL, 1.59 M in hexane, 3.76 mmol) was added slowly at –78 °C under argon to a solution of benzyl ether (+)-4 (1.71 g, 3.99 mmol) in THF (8.40 mL). The reaction mixture was stirred for 45 min at the same temperature, after which BF3·OEt2 (0.487 mL, 3.88 mmol) was added dropwise. Stirring was continued for 15 min, and then γ-lactone 7 (269 mg, 1.14 mmol) in THF (3.00 mL) was added. The resulting mixture was warmed to room temperature and stirred for 1 h, after which a solution of saturated aqueous NH4Cl solution/aqueous NH3 solution (1:8, v/v, 4.0 mL) was added. The mixture was allowed to warm to room temperature and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified with flash column chromatography on silica gel (hexane/EtOAc = 3:1 to 1:1) to give α,β-unsaturated ynone 8 (545 mg, 72% yield) as a colorless oil; Rf = 0.55 (hexane/EtOAc = 1:1); [α]D 25 +38.5 (c 2.16, CHCl3). IR (neat): νmax = 3434, 3069, 3031, 2929, 2857, 2209, 1756, 1676, 1112 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.63–7.60 (m, 4 H), 7.43–7.28 (m, 16 H), 4.78 (d, J = 11.6 Hz, 1 H), 4.61 (dd, J = 5.7, 7.9 Hz, 1 H), 4.53 (s, 2 H), 4.50 (d, J = 11.6 Hz, 1 H), 4.07 (m, 1 H), 3.86 (ddd, J = 4.7, 7.6, 10.5 Hz, 1 H), 3.79–3.66 (m, 4 H), 3.13 (d, J = 4.2 Hz, 1 H), 2.90 (d, J = 5.5 Hz, 1 H), 2.87 (dd, J = 8.3, 17.2 Hz, 1 H), 2.80 (dd, J = 4.2, 17.2 Hz, 1 H), 2.13–1.87 (m, 3 H), 1.78 (m, 1 H), 1.04–0.99 (m, 9 H). 13C NMR (100 MHz, CDCl3): δ = 186.2 (C), 137.6 (C), 137.2 (C), 135.5 (CH) × 4, 133.42 (C), 133.40 (C), 129.7 (CH), 129.6 (CH), 128.5 (CH) × 2, 128.4 (CH) × 2, 127.92 (CH) × 2, 127.87 (CH), 127.8 (CH), 127.70 (CH) × 2, 127.68 (CH) × 2, 127.66 (CH) × 2, 91.8 (C), 84.8 (C), 73.4 (CH2), 72.6 (CH), 71.4 (CH2), 69.8 (CH), 68.3 (CH2), 65.3 (CH), 59.3 (CH2), 49.0 (CH2), 38.0 (CH2), 32.9 (CH2), 26.8 (CH3) × 3, 19.1 (C). HRMS (ESI-TOF): m/z [M + Na]+ calcd for C41H48O6SiNa: 687.3118; found: 687.3119.
- 22 The relative configuration of the C6 spirocenter of the synthesized tricyclic lactones 9, 10, 12, and 13 is also supported by comparison of their NMR spectra with cephalosporolide E and F,12 whose structures have been determined by X-ray crystallography (see the Supporting Information).
- 23 Raghavan S, Samanta PK. Synlett 2013; 24: 1983
Goniofufurone:
Cephalosporolide I:
Ascospiroketal B: