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Synlett 2012; 23(7): 1021-1024
DOI: 10.1055/s-0031-1290527
letter
© Georg Thieme Verlag Stuttgart · New York

Enantiospecific First Total Synthesis of ent-Allothapsenol

A. Srikrishna*
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India, Fax: +91(80)3600683   Email: askiisc@gmail.com
,
K. Mahesh
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India, Fax: +91(80)3600683   Email: askiisc@gmail.com
› Author Affiliations
Further Information

Publication History

Received: 15 January 2012

Accepted after revision: 14 February 2012

Publication Date:
29 March 2012 (online)

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Dedicated to Professor A. J. Rao on the occasion of his 70th birthday

Abstract

The enantiospecific first total synthesis of the enantiomer of the irregular sesquiterpene from Ligusticumgrayi allo­thapsenol, starting from the readily available monoterpene (R)-carvone, is described, which confirmed the assumed absolute configuration of the natural product.

Key words

allothapsane - enantiospecific synthesis - irregular sesquiterpenes - carvone

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

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  • 6 Yields refer to isolated and chromatographically pure compounds. All the compounds exhibited spectral data [IR, HRMS, 1H NMR (400 MHz) and 13C NMR (100 MHz)] consistent with their structures. Selected Spectral Data for (1R,2R,4R,6R,9S)-4-Isopropenyl-1,6,7,7-tetramethyltricyclo[4.3.0.02,9]-nonan-8-one (10): [α]D 23 +116.9 (c 3.7, CHCl3). IR (neat): νmax= 1721 (C=O), 1381, 1017, 885 cm–1. 1H NMR (400 MHz, CDCl3): δ = 4.65 (1 H, s) and 4.58 (1 H, s) [C=CH 2], 2.10–1.95 (2 H, m), 1.87 (1 H, d, J= 10.1 Hz), 1.69 (3 H, s, olefinic CH3), 1.75–1.25 (3 H, m), 1.28 (3 H, s), 1.17 (3 H, s), 1.06 (3 H, s) and 0.81 (3 H, s) [4 × t-CH3], 0.68 (1 H, td, J = 14.0, 6.4 Hz). 13C NMR (100 MHz, CDCl3): δ = 217.5 (C=O), 148.6 (C=CH2), 108.9 (C=CH2), 58.3 (C, C-7), 40.3 (C), 39.4 (CH), 38.5 (CH), 38.1 (CH2), 30.1 (CH), 28.9 (C), 26.3 (CH3), 24.7 (CH2), 24.1 (CH3), 21.3 (CH3), 19.9 (CH3), 18.6 (CH3). HRMS: m/z calcd for C16H24O [M + Na]: 255.1725; found: 255.1726.(1R,6S)-1,6,9,9-Tetramethylbicyclo[4.3.0]non-4-ene-3,8-dione (3): [α]D 23 –35.5 (c 2.4, CHCl3). IR (neat): νmax = 1737 (C=O), 1683 (C=O), 1458, 1390, 1379, 1267, 1117, 1087, 785 cm–1. 1H NMR (400 MHz, CDCl3 + CCl4): δ = 6.66 (1 H, d, J = 10.1 Hz, H-5), 5.98 (1 H, d, J = 10.1 Hz, H-4), 2.63 (1 H, d, J = 19.2 Hz), 2.47 (1 H, d, J = 16.4 Hz), 2.46 (1 H, d, J = 19.2 Hz), 2.29 (1 H, d, J = 16.4 Hz), 1.34 (3 H, s), 1.10 (3 H, s), 1.06 (3 H, s), 1.01 (3 H, s) [4 × t-CH3]. 13C NMR (100 MHz, CDCl3 + CCl4): δ = 219.9 (C, C-8), 198.8 (C, C-3), 156.8 (CH, C-5), 126.5 (CH, C-4), 53.3 (C), 48.6 (CH2), 47.8 (C), 45.0 (CH2), 41.1 (C), 25.3 (CH3), 22.8 (CH3), 22.6 (CH3), 19.5 (CH3). HRMS: m/z calcd for C13H18O2 [M + Na]: 229.1204; found: 229.1206. (1R,2R,3S,6R)-3-Hydroxy-1,2,6,9,9-pentamethylbicyclo-[4.3.0]nonan-8-one (21): [α]D 22 –54.4 (c 4.0, CHCl3). IR (neat): νmax = 3510 (OH), 1719 (C=O), 1381, 1246, 1227, 963 cm–1. 1H NMR (400 MHz, CDCl3): δ = 3.84 (1 H, br s, CHOH), 2.66 (1 H, d, J = 17.6 Hz, H-7A), 1.95 (1 H, ddd, J = 14.2, 9.3, 7.5 Hz), 1.86 (1 H, d J = 17.6 Hz, H-7B), 1.74–1.68 (2 H, m), 1.60 (1 H, br s), 1.33–1.28 (1 H, m), 1.10–1.05 (15 H, m, 4 × t-CH3 and s-CH3). 13C NMR (100 MHz, CDCl3): δ = 224.4 (C, C=O), 72.0 (CH, C-3), 54.1 (C), 48.3 (C), 47.9 (CH2), 40.1 (C), 38.1 (CH), 29.2 (CH2), 28.4 (CH2), 28.1 (CH3), 26.1 (CH3), 25.9 (CH3), 15.9 (CH3), 15.2 (CH3). HRMS: m/z calcd for C14H24O2Na [M + Na]: 247.1674; found: 247.1672.(1R,6R)-1,2,6,9,9-Pentamethyl-8-methylenebicyclo-[4.3.0]non-2-ene [Allothapsa-2,8(12)-diene (19)]: [α]D 22 –11.5 (c 1.1, CHCl3). IR (neat): νmax = 3069, 1648, 1377, 1075, 879 cm–1. 1H NMR (400 MHz, CDCl3): δ = 5.40 (1 H, br s, H-3), 4.84 (1 H, d, J= 2.2. Hz) and 4.79 (1 H, d, J = 2.3 Hz), 2.57 (1 H, dt, J = 15.6, 2.2 Hz) and 2.04 (1 H, d, J = 15.6 Hz) [H-7], 2.15–1.98 (1 H, m), 1.95–1.80 (1 H, m), 1.80–1.65 (1 H, m), 1.66 (3 H, s, vinylic CH3), 1.15–1.00 (1 H, m), 1.12 (3 H, s), 1.11 (3 H, s), 0.99 (3 H, s) and 0.90 (3 H, s) [4 × t-CH3]. 13C NMR (100 MHz, CDCl3): δ = 162.9 (C, C-8), 137.1 (C, C-2), 121.7 (CH, C-3), 104.6 (CH2, C=CH2), 51.4 (C, C-1), 47.2 (CH2), 46.7 (C), 41.2 (C), 32.3 (CH2), 31.5 (CH3), 30.3 (CH3), 22.1 (2 C, CH3 and CH2), 21.5 (CH3), 19.2 (CH3). MS: m/z (%) = 204 (100) [M+], 189 (12), 166 (22), 135 (18), 121 (100).(1R,6R,8S)-1,2,6,9,9-Pentamethylbicyclo[4.3.0]nona-2-ene-8-methanol [8-Epiallothapsenol (20)]: [α]D 22 –5.4 (c 0.4, CHCl3). IR (neat): νmax = 3338 (OH), 1545, 1377, 1083, 1067, 1018, 818, 669 cm–1. 1H NMR (400 MHz, C6D6): δ = 5.46 (1 H, br s, olefinic H), 3.51 (1 H, dd, J = 10.2, 5.8 Hz), 3.23 (1 H, dd, J= 10.2, 7.9 Hz), 2.13–1.76 (2 H, m), 1.74–1.68 (2 H, m), 1.67 (3 H, s, vinylic CH3), 1.33–1.30 (2 H, m), 1.23 (1 H, dd, J= 13.3, 9.8 Hz), 1.06 (3 H, s), 0.93 (3 H, s) 0.90 (3 H, s), 0.86 (3 H, s) [4 × t-CH3]. 13C NMR (100 MHz, C6D6): δ = 138.7 (C, C-2), 124.2 (CH, C-3), 64.9 (CH2, CH2OH), 53.6 (C), 49.2 (CH), 46.2 (C), 44.9 (CH2), 42.0 (C), 38.9 (CH2), 28.4 (CH3), 25.9 (CH3), 23.2 (CH2), 22.7 (CH3), 21.8 (CH3), 20.4 (CH3).(1R,6R,8R)-1,2,6,9,9-Pentamethylbicyclo[4.3.0]nona-2-ene-8-methanol [ent-Allothapsenol (ent-1)]: [α]D 22 –28.5 (c 0.3, CHCl3). IR (neat): νmax = 3342 (OH), 1376, 1074, 1017, 817 cm–1. 1H NMR (400 MHz, C6D6): δ = 5.42 (1 H, br s, olefinic H), 3.45 (1 H, dd, J = 10.4, 7.0 Hz), 3.26 (1 H, dd, J = 10.3, 6.7 Hz), 2.10–1.75 (4 H, m), 1.61 (3 H, s, vinylic CH3), 1.40 (1 H, br s), 1.35 (1 H, dd, J = 12.5, 5.3 Hz), 1.25 (1 H, t, J = 12.7 Hz), 1.12 (3 H, s), 0.96 (3 H, s), 0.86 (3 H, s), 0.85 (3 H, s) [4 × t-CH3]. 13C NMR (100 MHz, C6D6): δ = 137.7 (C, C-2), 122.2 (CH, C-3), 64.6 (CH2, CH2OH), 52.5 (C), 50.7 (CH), 44.2 (C), 42.8 (CH2), 42.5 (C), 33.6 (CH3), 32.9 (CH2), 23.5 (CH3), 23.3 (CH3), 22.7 (CH2), 21.7 (CH3), 20.1 (CH3)
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