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Synlett 2020; 31(17): 1730-1734
DOI: 10.1055/s-0040-1706405
DOI: 10.1055/s-0040-1706405
letter
Total Synthesis of Ascospiroketal B
Weitere Informationen
Publikationsverlauf
Received: 15. Juni 2020
Accepted after revision: 23. Juni 2020
Publikationsdatum:
30. Juli 2020 (online)
![](https://www.thieme-connect.de/media/synlett/202017/lookinside/thumbnails/st-2020-u0345-l_10-1055_s-0040-1706405-1.jpg)
Abstract
An enantioselective total synthesis of the marine tricyclic polyketide ascospiroketal B, previously isolated from the marine-derived fungus Ascochyta salicorniae, was accomplished in 21 steps by using an improved route. The intriguing 5,5-spiroketal-cis-fused-γ-lactone core was constructed through rearrangement of an epoxide, in conjunction with an acid-mediated spiroketalization.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1706405.
- Supporting Information
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References and Notes
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- 17 Spiroketals 19 and 20 A solution of ketone 18 (58.4 mg, 62.3 μmol) in MeOH (300 μL) and THF (900 μL) was added to 2.0 M aq HCl (10.0 μL) at 30 °C, and the mixture was stirred for 3 h. The reaction was quenched with 2.0 M aq NaOH, and the mixture was diluted with Et2O. The organic layer was washed with H2O and brine, dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, hexane–EtOAc (3:2)] to afford spiroketals 19 and 20. Spiroketal 19 Colorless oil; yield: 12.4 mg (35%); Rf = 0.15 (hexane–EtOAc, 2:1); [α]D 25 +18.6 (c 1.32, CHCl3). IR (neat): 3435, 2959, 2933, 2588, 1776 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.64–7.58 (m, 4 H), 7.47–7.36 (m, 6 H), 6.54 (ddt, J = 1.0, 11.2, 15.0 Hz, 1 H), 6.16 (t, J = 11.2 Hz, 1 H), 5.69 (dd, J = 7.4, 15.0 Hz, 1 H), 5.52 (dt, J = 8.0, 11.0 Hz, 1 H), 5.22 (ddd, J = 2.2, 4.6, 6.9 Hz, 1 H), 4.68 (d, J = 4.5 Hz, 1 H), 4.59 (q, J = 7.1 Hz, 1 H), 3.88 (sextet, J = 6.2 Hz, 1 H), 3.77 (d, J = 9.7 Hz, 1 H), 3.62 (d, J = 9.7 Hz, 1 H), 2.65 (dd, J = 7.0, 15.0 Hz, 1 H), 2.40–2.04 (m, 6 H), 1.69 (m, 1 H), 1.26 (br s, 1 H), 1.23 (d, J = 6.2 Hz, 3 H), 1.03 (s, 3 H), 0.96 (s, 9 H). 13C NMR (100 MHz, CDCl3): δ = 180.2 (C), 135.7 (CH × 2), 135.4 (CH × 2), 133.7 (CH), 132.6 (C), 131.7 (C), 130.5 (CH), 130.0 (CH), 129.9 (CH), 128.3 (CH), 127.9 (CH × 4), 126.8 (CH), 115.1 (C), 83.7 (CH), 82.0 (CH), 79.2 (CH), 69.4 (CH2), 67.6 (CH), 51.0 (C), 42.4 (CH2), 37.5 (CH2), 35.1 (CH2), 31.1 (CH2), 26.7 (CH3 × 3), 22.9 (CH3), 19.1 (C), 13.6 (CH3). HRMS (ESI–TOF): m/z [M + Na]+ calcd for C34H44NaO6Si: 599.2805; found: 599.2808. Spiroketal 20 Colorless oil; yield: 12.8 mg (36%); Rf = 0.10 (hexane–EtOAc, 2:1); [α]D 25 –5.04 (c 1.16, CHCl3). IR (neat): 3435, 2963, 2933, 2858, 1773 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.64–7.58 (m, 4 H), 7.47–7.36 (m, 6 H), 6.49 (ddt, J = 1.2, 11.2, 15.2 Hz, 1 H), 6.16 (t, J = 11.1 Hz, 1 H), 5.69 (dd, J = 5.2, 15.2 Hz, 1 H), 5.45 (m, 1 H), 5.14 (t, J = 5.1 Hz, 1 H), 4.68 (d, J = 5.0 Hz, 1 H), 4.52 (quint, J = 7.1 Hz, 1 H), 3.88–3.75 (m, 2 H), 3.57 (d, J = 9.7 Hz, 1 H), 2.55–2.44 (m, 2 H), 2.28–2.02 (m, 5 H), 1.83 (m, 1 H), 1.62 (br s, 1 H), 1.22 (d, J = 6.2 Hz, 3 H), 1.13 (s, 3 H), 1.04 (s, 9 H). 13C NMR (100 MHz, CDCl3): δ = 180.3 (C), 135.6 (CH × 2), 135.5 (CH × 2), 133.3 (CH), 132.8 (C), 131.9 (C), 130.3 (CH), 130.0 (CH), 129.9 (CH), 128.1 (CH), 127.89 (CH × 2), 127.86 (CH × 2), 126.0 (CH), 115.1 (C), 85.3 (CH), 81.8 (CH), 81.0 (CH), 70.1 (CH2), 68.0 (CH), 51.3 (C), 41.7 (CH2), 37.8 (CH2), 36.2 (CH2), 31.3 (CH2), 26.8 (CH3 × 3), 22.6 (CH3), 19.2 (C), 14.1 (CH3). LRMS (ESI–TOF): m/z (%) = 599 (100) [M + Na]+. HRMS (ESI-TOF): m/z [M + Na]+ calcd for C34H44NaO6Si: 599.2805; found: 599.2808.