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Synlett 2002(4): 0583-0587
DOI: 10.1055/s-2002-22700
LETTER
© Georg Thieme Verlag Stuttgart · New York

An IMDA Approach to Tigliane and Daphnane Diterpenoids: Generation of Rings A, B and C Incorporating C-18

Philip C. Bulman Page*, Colin M. Hayman, Heather L. McFarland, David J. Willock, Natasha M. Galea
Department of Chemistry, Loughborough University, Loughborough, Leicestershire LE11 3TU, England
e-Mail: p.c.b.page@lboro.ac.uk;
Further Information

Publication History

Received 5 February 2002
Publication Date:
05 February 2007 (online)

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Abstract

A synthesis of the tricyclic ring system of the daphnane and tigliane diterpenes, incorporating C-18 and the C-13 oxygen functionality found in phorbol and related compounds is described. The convergent synthesis utilizes an intramolecular Diels-Alder reaction as the key stereocontrolling step.

Key words

phorbol - synthesis - tigliane - daphnane - IMDA

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1

Department of Chemistry, University of Cardiff, P.O. Box 912, Cardiff CF1 3TB, Wales.

15

(±)-(3a S ,6a S ,10a R ,10b S )-3-Oxo-8-triisopropylsilyloxy-1,2,3a,4,6,6a,9,10,10a,10b-decahydro-3 H -benzo[ e ]azulene-5,5,10-tricarboxylic Acid Diethyl Ester Methyl Ester (8a) and (±)-(3a S ,6a R ,10a R ,10b S )-3-Oxo-8-triisopropylsilyloxy-1,2,3a,4,6,6a,9,10,10a,10b-decahydro-3 H -benzo[ e ]azulene-5,5,10-tricarboxylic Acid Diethyl Ester Methyl Ester (8b) NB IUPAC-style numbering is used here for clarity. A screw-cap test-tube, rinsed sequentially with triethylamine and dry toluene, was charged with 16 (484 mg, 0.84 mmol), hydroquinone (4 mg, 0.04 mmol) and dry toluene (5 mL). The mixture was irradiated with ultrasound for 10 min while under a stream of nitrogen. The test-tube was sealed and heated at 160 °C for 72 h. The reaction mixture was cooled and concentrated and the crude product was purified by silica gel column chromatography [10% ethyl acetate/light petroleum (40-60 °C)] to afford a mixture of 8a and 8b (437 mg, 93%) as a colourless oil, νmax/cm-1(neat): 2945, 2866, 1730, 1683, 1464, 1251, 1206, 1162, 883, 806, 682. 1H NMR (600 MHz, C6D6): δ = 0.84 (3 H, t, J = 7.1 Hz, CH 3CH2), 0.86-0.94 (4 H, m, 1 of 1-H8b, CH 3CH2), 0.96 (3 H, t, J = 6.9 Hz, CH 3CH2), 1.00-1.21 (47 H, m, 1 × CH 3CH2, 1 of 1-H8a, 10b-H8a, 6 × CH(CH 3)2), 1.34 (1 H, dd, J = 11.8, 14.1 Hz, 1 of 4-H8b), 1.53, (1 H, ddd, J = 9.1, 9.9, 10.8, 10a-H8a), 1.58-1.71 (5 H, m, 1 of 1-H8a, 1 of 2-H8a, 1 of 1-H8b, 1 of 2-H8b, 10b-H8b), 1.73 (1 H, dd, J = 10.2, 15.2, 4-H8a), 1.78-1.82 (1 H, m, 10a-H8b), 1.93-2.04 (3 H, m, 1 of 2-H8b, 1 of 2-H8a, 3a-H8a), 2.07 (1 H, dd, J = 2.6, 10.2, 15.1 Hz, 1 of 6-H8a), 2.13-2.24 (4 H, m, 3a-H8b, 1 of 6-H8b,1 of 9-H8b, 6a-H8a), 2.33 (1 H, ddd, J = 1.7, 5.0, 16.6 Hz, 1 of 9-H8a), 2.43-2.48 (3 H, m, 1 of 6-H8b, 6a-H8b, 10-H8a), 2.59 (1 H, ddd, J = 5.3, 10.1, 10.1 Hz, 10-H8b), 2.64 (1 H, d, J = 15.1 Hz, 6-H8a), 2.69 (1 H, dddd, J = 2.2, 3.7, 11.3, 16.6 Hz, 1 of 9-H8a), 2.76 (1 H, dddd, J = 1.8, 1.8, 10.1, 17.0 Hz, 1 of 9-H8b), 3.30, (3 H, s, CO2CH 3), 3.31, (3 H, s, CO2CH 3), 3.38 (1 H, d, J = 15.2 Hz, 1 of 4-H8a), 3.45 (1 H, br ddd, J = 2.3, 2.3, 14.1 Hz, 1 of 4-H8b), 3.81-4.01 (6 H, m, 6 of CH3CH 2), 4.09 (1 H, qd, J = 7.1, 10.9 Hz, 1 of CH3CH 2), 4.15 (1 H, qd, J = 7.0, 10.5 Hz, 1 of CH3CH 2), 5.03 (1 H, dd, J = 1.8, 5.2 Hz, 7-H8b), 5.11 (1 H, dd, J = 2.2, 2.4 Hz, 7-H8a); 13C NMR (150 MHz, C6D6): δ = 13.0 (CH(CH3)2, 13.9, 14.0, 14.1, 14.2 (4 × CH2 CH3), 18.2 (CH(CH3)2), 26.2 (1-C8a), 28.6 (1-C8b), 32.3 (4-C8a), 33.4 (9-C8b), 34.6 (9-C8a), 34.8 (6a-C8b), 36.7 (2-C8a), 36.8 (6-C8b), 37.0 (3a-C8b), 37.2 (4-C8b), 37.5 (2-C8b), 42.5 (6-C8a), 43.0 (10-C8b), 44.8 (10a-C8b), 45.6 (10b-C8b), 47.2 (10-C8a), 49.1 (10a-C8a), 49.8 (6a-C8a), 51.0 (10b-C8a), 51.2, 51.3 (2 x CO2 CH3), 51.9 (3a-C8a), 55.9 (5-C8a), 57.1 (5-C8b), 61.2, 61.3, 61.35, 61.44 (4 × CH2CH3), 107.7 (7-C8b), 109.2
(7-C8a), 148.3 (8-C8a), 148.9 (8-C8b), 170.9, 171.9, 172.2, 172.3 (4 × CO2C2H5), 175.1, 175.6 (2 × CO2CH3), 214.2 (3-C8a), 215.6 (3-C8b). MS (EI): m/z = 578 (14) [M+], 535 (35), 519 (17), 324 (30), 256 (77), 69 (100). C31H50O8Si requires 578.3275, found 578.3284.