Synlett 2008(18): 2773-2776  
DOI: 10.1055/s-0028-1087296
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Stereoselective Approach for the Total Synthesis of Clonostachydiol

J. S. Yadav*, T. Swamy, B. V. Subba Reddy
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax: +91(40)27160512; e-Mail: yadav@iict.res.in;
Further Information

Publication History

Received 5 June 2008
Publication Date:
21 October 2008 (online)

Abstract

A stereoselective synthesis of clonostachydiol is accomplished using readily available (±)-epichlorohydrin as a precursor. The synthesis involves direct and straightforward reactions such as Sharpless asymmetric epoxidation, iodination, stereoselective opening of epoxide with allylmagnesium chloride and Sharpless asymmetric dihydroxylation.

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Compound 15: [α]D +7.5 (c = 1, CDCl3). ¹H NMR (300 MHz, CDCl3): δ = 6.95 (dd, J = 15.8, 4.5 Hz, 1 H), 6.00 (d, J = 15.8 Hz, 1 H), 4.25 (dd, J = 6.7, 4.5 Hz, 1 H), 3.75-3.85 (m, 1 H), 3.72 (s, 3 H), 1.15 (d, J = 6.7 Hz, 3 H), 0.95 (s,
9 H), 0.10 (s, 3 H), 0.06 (s, 3 H). ¹³C NMR (50 MHz, CDCl3): δ = 166.4, 147.4, 121.6, 75.6, 70.2, 51.3, 25.6, 18.0, -4.6. IR (Neat): 3452, 2928, 2885, 1714, 1642, 1412, 1225, 915 cm. MS (ESI): m/z = 297 [M + Na+]. HRMS: m/z calcd for C13H26O4SiNa: 297.1498; found: 297.1491.
Compound 21: [α]D +7.5 (c = 0.6, CDCl3). ¹H NMR (300 MHz, CDCl3): δ = 7.22-7.35 (m, 5 H), 6.90 (dd, J = 15.6, 6.2 Hz, 1 H), 5.95 (d, J = 15.6 Hz, 1 H), 4.50-4.62 (m, 2 H), 4.45 (d, J = 6.6 Hz, 2 H), 4.06-4.15 (m, 1 H), 3.45-3.55 (m, 1 H), 3.35 (s, 3 H), 1.50-1.75 (m, 4 H), 1.20 (d, J = 6.0 Hz, 3 H). ¹³C NMR (50 MHz, CDCl3): δ = 173.4, 152.2, 130.0, 129.6, 129.4, 123.5, 97.2, 77.0, 76.1, 72.5, 55.0, 34.5, 32.2, 23.6. MS (ESI): m/z = 309 [M+ + 1], 331 [M+ + Na]. HRMS: m/z calcd for C17H24O5Na: 331.1521; found: 331.1519.
Compound 1: [α]D +101 (c = 1, MeOH). ¹H NMR (300 MHz, CDCl3): δ = 6.85 (dd, J = 14.3, 4.3 Hz, 1 H), 6.78 (dd, J = 15.1, 6.1 Hz, 1 H), 6.08 (d, J = 14.3 Hz, 1 H), 5.95 (d, J = 15.1 Hz, 1 H), 4.90-4.98 (m, 1 H), 4.15-4.25 (m, 2 H), 3.85-3.95 (m, 1 H), 1.55-1.68 (m, 4 H), 1.25 (d, J = 6.0 Hz, 3 H, Me), 1.25 (d, J = 6.0 Hz, 3 H, Me). IR (Neat): 3350, 2984, 2918, 1709, 1643, 1252, 1175 cm. LCMS: m/z = 307 [M+ + Na].