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Synlett 2007(9): 1464-1466  
DOI: 10.1055/s-2007-980351
LETTER
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Total Synthesis of (+)-Goniothalesdiol and (+)-2,5-epi-­Goniothalesdiol from d-Mannitol

Subhash Ghosh*, Chapala Nageswara Rao, Samit Kumar Dutta
Division of Organic Chemistry-III, Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India
Fax: +91(40)27193108; e-Mail: subhashbolorg3@yahoo.com;
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Publication History

Received 22 February 2007
Publication Date:
23 May 2007 (online)

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Abstract

An efficient and practical total synthesis of (+)-gonio­thalesdiol and its 2,5-epi analogue is described herein. The key ­features include a diastereoselective reduction of C-5 keto with Zn(BH4)2 to generate the desired stereochemistry at C-5. The tetra­hydrofuran backbone of natural goniothalesdiol was synthesized under basic conditions via epoxide formation, followed by in situ 5-exo opening of the epoxide ring with γ-benzoyloxy oxygen upon ­debenzoylation. For the 2,5-epi analogue, the tetrahydrofuran ring was formed via acid-catalyzed acetonide deprotection followed by concomitant SN2 displacement of the O-mesyl group at C-5 center with C-2-γ-oxygen.

Key words

goniothalesdiol - Zn(BH4)2 reduction - cycloetherification - d-mannitol

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Spectral Data of Methyl 3-[2S,3S,4R,5R]-3,4-Dihydroxy-5-phenyltetrahydrofuran-2-yl)propionate (1): [α]D 27 +8.1 (c = 0.7, EtOH). IR (neat): 3429, 2951, 1736, 1441 cm-1. 1H NMR (600 MHz, CDCl3): δ = 7.42 (d, J = 7.3 Hz, 2 H), 7.35 (t, J = 7.3 Hz, 2 H, Ar), 7.29 (d, J = 7.3 Hz, 1 H), 4.60 (d, J = 4.6 Hz, 1 H), 4.04-4.10 (m, 3 H), 3.70 (s, 3 H), 2.63 (dt, J = 6.7, 17.1 Hz, 1 H), 2.51 (ddd, J = 6.7, 8.1, 17.1 Hz, 1 H), 2.12 (m, 1 H) 2.06 (dq, J = 6.7, 14.3 Hz, 1 H). 13C NMR (150 MHz, CDCl3): δ = 174.9, 139.7, 128.5, 127.8, 126.1, 85.9, 85.0, 80.7, 78.7, 52.0, 30.5, 23.4. MS (LCMS): m/z = 289 [M + Na]+.

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Spectral Data of Methyl 3-[2R,3S,4R,5S]-3,4-Dihydroxy-5-phenyltetrahydrofuran-2-yl)propionate (2): [α]D 27 +94.47 (c = 0.38, EtOH). IR (neat): 3420, 2951, 1724, 1440 cm-1. 1H NMR (600 MHz, CDCl3): δ = 7.30-7.40 (m, 5 H), 5.14 (d, J = 3.5 Hz, 1 H), 4.11 (dd, J = 1.2, 3.5 Hz, 1 H), 4.06 (dd, J = 1.2, 3.3 Hz, 1 H), 3.89 (ddd, J = 3.3, 6.2, 7.0 Hz, 1 H), 3.70 (s, 3 H), 2.52-2.64 (m, 2 H), 2.11-2.15 (m, 2 H). 13C NMR (150 MHz, CDCl3): δ = 174.2, 135.6, 128.6, 128.1, 126.8, 84.7, 82.9, 81.7, 80.1, 51.8, 30.6, 28.7. MS (LCMS): m/z = 289 [M + Na]+.