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Synlett 2008(14): 2103-2106  
DOI: 10.1055/s-2008-1078015
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Synthesis of the C(17)-C(27) Fragment of Bryostatin 1

Anthony P. Green, Simon Hardy, Eric J. Thomas*
The School of Chemistry, The University of Manchester, Manchester M13 9PL, UK
Fax: +44(161)2754939; e-Mail: e.j.thomas@manchester.ac.uk;
Further Information

Publication History

Received 8 July 2008
Publication Date:
31 July 2008 (online)

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Abstract

An approach to the C(17)-C(27) fragment of bryostatin 1, based on forming the C(19)-C(20) bond by reaction of an acyl carbanion equivalent at C(19) with an aldehyde, is described.

Key words

acetals - metathesis - natural products - stereoselective synthesis - total synthesis

    References and Notes

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15

To a solution of dithiane 23 (341 mg, 0.34 mmol) in THF (5.5 mL) and MeOH (5.5 mL) at 0 ˚C was added 2,6-lutidine (0.27 mL, 2.3 mmol) and mercury(II) perchlorate trihydrate (273 mg, 0.68 mmol). After stirring at 0 ˚C for 10 min, the reaction mixture was allowed to warm to r.t. and was stirred for 8 h. The resulting white suspension was filtered through Celite and partitioned between ether and sat. aq NaHCO3. After separation of the organic layer, the aqueous phase was extracted with Et2O. The combined organic extracts were dried (MgSO4), filtered, and concentrated under reduced pressure. Flash chromatography of the residue using Et2O (2%) in light PE as eluent afforded the acetal 3 (277 mg, 88%) as a colourless oil, R f  = 0.34 (light PE-Et2O, 15:1); [α]D ²4 -32 (c 0.5, CH2Cl2). IR: νmax = 2954, 2894, 2864, 1471, 1463, 1380, 1361, 1251, 1148, 1102, 1058, 939, 883, 859, 835, 775 cm-¹. ¹H NMR (500 MHz, C6D6): δ = 0.00 [9 H, s, Si(CH3)3], 0.15, 0.16, 0.17, 0.23 [each 3 H, s, Si(CH3)], 0.96 [2 H, m, CH 2Si(CH3)3], 1.01, 1.03 [each 9 H, s, SiC(CH3)3], 1.05-1.15 {21 H, m, Si[CH(CH3)2]3}, 1.31 (3 H, d, J = 6.0 Hz, 4′′′-H3), 1.52 (6 H, s, 2 × 1′-CH3), 1.68 (1 H, t, J = 12.5 Hz, 1′′′-H), 2.13 (1 H, dd, J = 10.5, 13.0 Hz, 1′′′-H′), 2.26 (1 H, dd, J = 3.0, 13.5 Hz, 5-H), 2.33 (1 H, t,
J = 12.5 Hz, 5-H′), 3.38 (3 H, s, OCH3), 3.47 (1 H, m, OCHHCH2Si), 3.75 (1 H, br. s, 2′-H), 3.82 (1 H, m, OCHHCH2Si), 4.03-4.21 (3 H, m, 6-H, 2′-H′ and 2′′′-H), 4.28 (1 H, dd, J = 5.5, 12.5 Hz, 2′′-H), 4.30-4.38 (3 H, m, 3-H, 2′′-H′ and 3′′′-H), 4.60, 4.63 (each 1 H, d, J = 12.5 Hz, CHHPh), 4.74 (1 H, d, J = 7.0 Hz, OCHHO), 4.91 (1 H, br d, J = 7.0 Hz, OCHHO), 5.75 (1 H, m, 1′′-H), 7.10 (1 H, t, J = 7.4 Hz, ArH), 7.21 (2 H, t, J = 7.5 Hz, ArH), 7.44 (2 H, d, J = 7.5 Hz, ArH). ¹³C NMR (75 MHz, C6D6): δ = -4.4, -4.2, -4.0, -3.4, -0.9, 12.7, 17.6, 18.7, 18.7, 18.8, 19.0, 21.9, 22.5, 26.6, 26.7, 31.9, 36.3, 46.7, 52.3, 60.1, 65.9, 68.7, 69.8, 73.9, 76.3, 76.9, 80.1, 97.2, 104.2, 127.8, 127.9, 128.9, 137.2, 140.4. MS (ES+): m/z (%) = 962 (100) [M + 23], 963 (70), 964 (38), 965 (13).