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Synlett 2017; 28(10): 1187-1190
DOI: 10.1055/s-0036-1588723
letter
© Georg Thieme Verlag Stuttgart · New York

A New Process for the Total Synthesis of Sparstolonin B

Xiaohang Tang
,
Le Tong
,
Mengyi Yao
,
Qiaoli Liang
,
Xiaolong Wang
,
Haitao Yu*
Further Information

Publication History

Received: 04 January 2017

Accepted after revision: 27 January 2017

Publication Date:
23 February 2017 (online)

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Abstract

A novel and simple route was developed that gives sparstolonin B in high yields from affordable commercial compounds. A Diels–Alder strategy was used for the facile construction of the multisubstituted diphenyl ether. The xanthenone segment was obtained by cyclization in an intramolecular Friedel–Crafts reaction, followed by selective reduction of a ketone group and a transformation from a hydroxy group into a cyano group. The final part of the lactone was directly derived by the reduction of the cyano group with Raney nickel.

Key words

sparstolonin B - xanthenone - lactone - total synthesis - medicinal chemistry

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0036-1588723.
  • Supporting Information

Primary Data

    Primary data for this article are available online at http://www.thieme-connect.com/ejournals/toc/synthesis and can be cited using the following DOI: 10.4125/pd0087th.

  • Primary Data
 

  • References and Notes

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  • 2 New address: M.-Y. Yao, School of Life Sciences, Fudan University, 2005 Songhu Rd, Yangpu District, Shanghai, 200438, P. R. of China.
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  • 16 4,10-Dimethoxy-3H-pyrano[3,4,5-kl]xanthen-3-one (10) A mixture of nitrile 2 (8.8 g, 0.027 mol), pyridine (3.2 g, 0.04 mol), NaH2PO2 (4.75 g, 0.054 mol), AcOH (66 mL), H2O (54 mL), and Raney nickel catalyst (1 g) was stirred for 5 h at 0 °C under argon. The mixture was then diluted with EtOAc (100 mL) and H2O (100 mL), then filtered. The filtrate was extracted with EtOAc (2 × 100 mL), and the organic phase was washed with H2O (80 mL), dried (Na2SO4), and concentrated under reduced pressure. The crude residue was purified by flash chromatography [silica gel, PE–EtOAc (5:1)] to give a pale-yellow solid; yield: 6.4 g (80 %); mp 201–203 °C. 1H NMR (400 MHz, CDCl3): δ = 7.49 (s, 1 H), 7.33 (d, J = 9.0 Hz, 1 H), 7.02 (dd, J = 9.0, 2.8 Hz, 2 H), 6.88 (d, J = 10.3 Hz, 2 H), 4.01 (s, 3 H), 3.85 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ = 157.80, 156.26, 155.75, 144.02, 142.10, 134.57, 122.84, 121.64, 118.24, 116.51, 114.98, 112.33, 108.63, 108.42, 104.97, 56.61, 55.75. HRMS (ESI): m/z [M + Na]+ calcd for C17H12NaO5: 319.0582; found: 319.0571. Sparstolonin B (SsnB) A 1.0 M soln of BBr3 in CH2Cl2 (85 mL, 0.085 mol) was added dropwise to a solution of xanthenone 10 (5.2 g, 0.017mol) in CH2Cl2 (180 mL) at –5 to 0 °C under argon, and the mixture was stirred for 1 h at r.t. The reaction was then quenched with ice–water (150 mL) and the mixture was extracted with CH2Cl2 (2 × 150 mL). The organic phase was washed with H2O (80 mL), dried (Na2SO4), and concentrated under reduced pressure. The crude residue was purified by flash chromatography [silica gel, PE–EtOAc (5:1)] to give a yellow solid; yield: 4.2 g (92%). 1H NMR (400 MHz, DMSO-d 6): δ = 10.37 (s, 1 H), 9.54 (s, 1 H), 7.99 (s, 1 H), 7.49 (d, J = 9.0 Hz, 1 H), 7.11 (d, J = 2.8 Hz, 1 H), 7.08 (d, J = 9.0 Hz, 1 H), 7.03 (d, J = 8.9 Hz, 1 H), 6.83 (dd, J = 8.9, 2.8 Hz, 1 H). 13C NMR (101 MHz, DMSO-d 6): δ = 164.30, 155.35, 154.14, 143.13, 140.89, 135.27, 123.86, 120.14, 118.55, 118.49, 117.53, 114.94, 109.86, 108.00, 105.02. HRMS (ESI): m/z [M + Na]+ calcd for C15H8NaO5: 291.0269; found: 291.0261.