Stereoselective Total Synthesis of (-)-9-Deoxygoniopypyrone

Kavirayani R. Prasad; Madhuri G. Dhaware

doi:10.1055/s-2007-973873

LETTER

Stereoselective Total Synthesis of (-)-9-Deoxygoniopypyrone

Kavirayani R. Prasad*, Madhuri G. Dhaware
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
e-Mail: prasad@orgchem.iisc.ernet.in;

Abstract

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Abstract

Stereoselective synthesis of (-)-9-deoxygoniopypyrone was achieved from the naturally occurring l-(+)-tartaric acid. Key step involves the elaboration of a γ-hydroxybutyramide to the title compound involving high-yielding stereoselective transformations.

Key words

styryllactone - (-)-9-deoxygoniopypyrone - stereoselective reduction - tartaric acid

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Referenzen

References and Notes

For a review on the cytotoxic activity and other bioactivity of styryllactones, see:

1a Mereyala HB. Joe M. Curr. Med. Chem. Anti-Cancer Agents 2001, 1: 293

1b Blàzquez MA. Bermejo A. Zafra-Polo MC. Cortes D. Phytochem. Anal. 1999, 10: 161

2 Fang X.-P. Anderson JE. Chang C.-J. McLaughlin JL. Fanwick PE. J. Nat. Prod. 1991, 54: 1034

For recent synthesis of 9-deoxygoniopypyrone, see:

3a Yamashita Y. Saito S. Ishitani H. Kobayashi S. J. Am. Chem. Soc. 2003, 125: 3793

3b Ramachandran PV. Chandra JS. Reddy MVR. J. Org. Chem. 2002, 67: 7547

3c Chen J. Lin G.-Q. Wang Z.-M. Liu H.-Q. Synlett 2002, 1265

3d Tsubaki M. Kanai K. Nagase H. Honda T. Tetrahedron 1999, 55: 2493

3e Survivet J.-P. Vatèle J.-M. Tetrahedron 1999, 55: 13011

3f Mukai C. Hirai S. Hanaoka M. J. Org. Chem. 1997, 62: 6619

4a Prasad KR. Gholap SL. Synlett 2005, 2260

4b Prasad KR. Gholap SL. J. Org. Chem. 2006, 71: 3643

5 For the synthesis of α,β-dihydroxy-γ-alkyl(aryl)-γ-butyrolactones from γ-hydroxybutyramides, see: Prasad KR. Chandrakumar A. Tetrahedron 2007, 63: 1798

6

To circumvent the use of expensive Grubbs’ second-generation catalyst in the synthesis of lactone 14, an alternate route for 14 from alcohol 12 was examined. As shown below (Scheme [4] ), homoallylic alcohol 12 was protected as its allyl ether, which underwent smooth RCM reaction with Grubbs’ first generation catalyst to yield the dihydropyran 15 in 90% yield. PCC oxidation of the dihydropyran 15 resulted in the lactone 14 in 44% yield (72% based on recovered starting material).

7

All new compounds exhibited satisfactory spectral data. Compound 8: [α]_D ²⁵ -44.0 (c = 1, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 7.25-7.48 (m, 5 H), 5.12 (d, J = 8.4 Hz, 1 H), 4.11 (d, J = 8.4 Hz, 1 H), 4.04 (dd, J = 0.9, 8.4 Hz, 1 H), 3.74 (s, 3 H), 3.25 (dd, J = 1.8, 9.0 Hz, 1 H, OH, exchangeable with D₂O), 1.55 (s, 3 H), 1.50 (s, 3 H). ¹³C NMR (75 MHz): δ = 172.7, 136.9, 128.6, 128.4, 126.6, 109.8, 83.6, 78.4, 67.6, 52.6, 27.1, 26.5. HRMS: m/z [M + Na] calcd for C₁₄H₁₈O₅: 289.1054; found: 289.1052. Compound 12: [α]_D ²⁵ -18.9 (c = 0.9, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 7.27-7.44 (m, 5 H), 5.68-5.84 (m, 1 H), 4.94-5.07 (m, 3 H), 3.76 (ddd, J = 1.2, 2.4, 8.4 Hz, 1 H), 3.58-3.68 (m, 1 H), 2.13-2.35 (m, 3 H), 1.58 (s, 3 H), 1.53 (s, 3 H). ¹³C NMR (75 MHz): δ = 137.6, 134.2, 128.6, 128.3, 126.9, 117.8, 109.2, 84.9, 79.3, 68.0, 39.6, 27.2, 27.0. HRMS: m/z [M + Na] calcd for C₁₅H₂₀O₃: 271.1312; found: 271.1310. Compound 14: [α]_D ²⁵ -5.0 (c = 0.4, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 7.31-7.46 (m, 5 H), 6.87 (ddd, J = 2.5, 5.9, 9.6 Hz, 1 H), 6.04 (dd, J = 2.5, 9.6 Hz, 1 H), 5.24 (d, J = 8.6 Hz, 1 H), 4.42 (ddd, J = 2.5, 4.2, 11.7 Hz, 1 H), 3.82 (dd, J = 2.0, 8.6 Hz, 1 H), 2.63-2.75 (m, 1 H), 2.20-2.30 (m, 1 H), 1.59 (s, 3 H), 1.55 (s, 3 H). ¹³C NMR (100 MHz): δ = 163.6, 144.8, 137.1, 128.8, 128.6, 126.8, 121.2, 110.0, 83.9, 77.5, 73.5, 27.3, 26.7, 26.6. HRMS: m/z [M + Na] calcd for C₁₆H₁₈O₄: 297.1105; found: 297.1103.