Synlett 2012; 23(12): 1793-1796
DOI: 10.1055/s-0031-1290402
letter
© Georg Thieme Verlag Stuttgart · New York

Serendipitous Synthesis and Configurational Assignment of (–)-Gabosine J

Tony K. M. Shing*
Department of Chemistry and Center of Novel Functional Molecules, The Chinese University of Hong Kong, Shatin, Hong Kong, P. R. of China, Fax: +85226035057   Email: tonyshing@cuhk.edu.hk
,
Y. Chen
Department of Chemistry and Center of Novel Functional Molecules, The Chinese University of Hong Kong, Shatin, Hong Kong, P. R. of China, Fax: +85226035057   Email: tonyshing@cuhk.edu.hk
,
Ho T. Wu
Department of Chemistry and Center of Novel Functional Molecules, The Chinese University of Hong Kong, Shatin, Hong Kong, P. R. of China, Fax: +85226035057   Email: tonyshing@cuhk.edu.hk
› Author Affiliations
Further Information

Publication History

Received: 22 March 2012

Accepted after revision: 06 May 2012

Publication Date:
29 June 2012 (online)


Abstract

2-epi-Gabosine I, unambiguously synthesized from benzyl d-mannopyranoside in nine steps with 34% overall yield, has been shown to be identical to gabosine J by NMR spectral analysis, thereby indicating that the relative stereochemistry of gabosine J was incorrectly determined formerly as a syn-triol. The relative and absolute configurations of (–)-gabosine J are now revised and confirmed as (2S,3S,4R)-trihydroxy-5-hydroxymethylcyclohex-5-en-1-one. Since the specific rotation of the natural product has not been recorded, the absolute configuration of natural gabosine J is either (–)-gabosine J or its enantiomer.

Supporting Information

 
  • References

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  • 16 Synthesis of Enone 14 To a mixture of 3 Å MS (200 mg), CH2Cl2 (3 mL), and DMSO (0.36 ml, 5.00 mmol) was added dropwise TFAA (0.42 mL, 3.00 mmol) at –78 °C under N2. After 30 min, a solution of the diols 12 (0.265 mg, 0.45 mmol) in CH2Cl2 (2 mL) was added dropwise. The reaction mixture was stirred for an additional 5 h at –78 °C, and DIEPA (1.75 mL, 10.00 mmol) was added dropwise. The reaction mixture was stirred at –78 °C for 15 min and then warmed to 25 °C over a period of 2 h. LiCl (38 mg, 0.90 mmol) and Et3N (0.25 mL, 1.80 mmol) was added to the reaction mixture, and stirring was continued for an additional 1.5 h at the same temperature. The reaction mixture was then filtered, and the filtrate was concentrated under vacuum. Flash chroma-tography (hexane–EtOAc = 8:1) of the crude residue yielded enone 14 (0.144 mg, 70%) as a yellow oil. [α]D 20 137.4 (c 1.23, CHCl3). Rf = 0.6 (n-hexane–EtOAc, 3:1). IR (thin film): 2953, 2886, 2857, 1685, 1630, 1472, 1378, 1257, 1164, 1114, 1034 cm–1. 1H NMR (300 MHz, CDCl3): δ = 0.05 (3 H, s), 0.06 (3 H, s), 0.88 (9 H, s), 1.17 (3 H, t, J = 7.2 Hz), 1.31 (3 H, s), 1.30 (3 H, s), 3.23 (3 H, s), 3.27 (3 H, s), 3.52–3.63 (2 H, m), 3.94 (1 H, dd, J = 2.7, 13.2 Hz), 4.12 (1 H, dd, J = 1.5, 3.0 Hz), 4.33 (1 H, dt, J = 1.8, 18.3 Hz), 4.58 (1 H, d, J = 18.3 Hz), 4.80 (2 H, s), 4.93 (1 H, dt, J = 1.2, 8.7 Hz), 6.12 (1 H, dd, J = 1.2, 2.1 Hz). 13C NMR (75.47 MHz, CDCl3): δ = –4.9, –4.8, 15.5, 18.2, 18.3, 18.8, 26.4, 26.5, 48.7, 48.7, 61.4, 64.1, 66.0, 71.6, 77.3, 95.1, 100.5, 100.9, 122.2, 162.6, 194.7. ESI-MS: m/z (%) = 483 (100) [M + Na]+. ESI-HRMS: m/z calcd for C22H40O8Si [M + Na]+: 483.2385; found: 483.2392
  • 17 Synthesis of (–)-Gabosine J (4) To enone 14 (35 mg, 0.08 mmol) was added TFA (2 mL) and H2O (0.1 mL) at r.t. The resulting solution was stirred for 5 min at r.t. Concentration of the solution followed by flash chromatography (CHCl3–MeOH = 8:1) yielded (–)-gabosine J (4; 12 mg, 96%) as colorless oil. [α]D 20 –75.0 (c 0.70, MeOH). Rf = 0.3 (CHCl3–MeOH = 4:1). IR (thin film): 3311, 2912, 1682, 1438, 1384, 1119, 1087, 1040 cm–1. 1H NMR (300 MHz, MeOD): δ = 4.16–4.25 (3 H, m), 4.41 (1 H, dd, J = 17.8, 1.7 Hz), 4.55 (1 H, d, J = 2.5 Hz), 6.10 (1 H, t, J = 1.7 Hz). 13C NMR (75.47 MHz, MeOD): δ = 63.2, 69.9, 73.8, 76.5, 122.1, 162.2, 199.9. ESI-MS: m/z (%) = 197 (100) [M + Na]+. ESI-HRMS: m/z calcd for C7H10O5 [M + Na]+: 197.0420; found: 197.0423