Download PDF
Synlett 2008(8): 1199-1201  
DOI: 10.1055/s-2008-1072733
LETTER
© Georg Thieme Verlag Stuttgart · New York

The First Total Syntheses of the Sesquiterpenes (±)-1,10;7,10-Bisepoxy-1,10-seco-calamanene and (±)-6,7;7,10-Bisepoxy-6,7-seco-calamanene

A. Srikrishna*, G. Ravi, Hema S. Krishnan
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
Further Information

Publication History

Received 15 January 2008
Publication Date:
16 April 2008 (online)

    Permissions and Reprints All articles of this category

Abstract

First total syntheses of the tricyclic sesquiterpenes mentioned in the title containing a benzo-fused 2,8-dioxabicyclo[3.2.1]octane framework, confirming the structures of the natural products, are described.

Key words

natural products - sesquiterpenes - total synthesis - intramolecular acetalisation - dioxabicyclo[3.2.1]octanes

    References and Notes

  • 1 Weyerstahl P. Schweiger R. Schwope I. Hashem MdA. Liebigs Ann.  1995,  1389 ; and references cited therein
    Crossref
  • 2 Weyerstahl P. Marschall H. Thefeld K. Subba GC. Flavour Fragr. J.  1998,  13:  377 
    CrossrefSearch in Google Scholar
  • 3 Srikrishna A. Rao MS. Synlett  2004,  374 
    Thieme Connect
  • 4 Tsuji T. Organic Synthesis with Palladium Compounds   Springer; New York: 1980.  p.6-12  
  • 6 Cuong NM. Soejarto DD. Pezzuto JM. Fong HHS. J. Nat. Prod.  2003,  66:  609 
    CrossrefPubMedSearch in Google Scholar
  • 7 Although litseachromolaevane A (10) was reported as a new compound in 2003, it is the same as sesquichamaenol reported earlier from Chamaecyparis forrnosensis Matsum. See: Ando M. Ibe S. Kagabu S. Nakagawa T. Asao T. Takase K. J. Chem. Soc., Chem. Commun.  1970,  1538 
  • 8 Nemoto H. Miyata J. Fukumoto K. Tetrahedron  1996,  52:  10363 
    CrossrefSearch in Google Scholar
5

Yields refer to isolated and chromatographically pure compounds. All the compounds exhibited spectral data (IR, 1H NMR, 13C NMR, and HRMS) consistent with their structures.
Selected Spectral Data
Alcohol 7: IR (neat): νmax = 3531, 1639, 810 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.12 (1 H, s), 7.00-6.90 (2 H, m), 5.82-5.72 (1 H, m), 5.15 (2 H, br s), 4.90 (1 H, d, J = 15.9 Hz), 4.86 (1 H, d, J = 9.0 Hz), 3.45 (3 H, s), 3.11 (1 H, br s), 2.29 (3 H, s), 2.30-1.95 (3 H, m), 1.81 (1 H, td, J = 12.9 and 4.2 Hz), 1.70-1.60 (1 H, m), 0.96 (3 H, d, J = 6.6 Hz), 0.72 (3 H, d, J = 6.9 Hz). 13C NMR (75 MHz, CDCl3): δ = 152.4 (C), 139.4 (CH), 132.7 (C), 130.5 (C), 129.0 (CH), 128.1 (CH), 114.3 (CH), 114.1 (CH2), 94.5 (CH2), 79.8 (C), 56.0 (CH3), 36.6 (CH2), 36.2 (CH), 28.9 (CH2), 20.9 (CH3), 17.7 (CH3), 16.8 (CH3). HRMS: m/z calcd for C17H26O3Na [M + Na]: 301.1780; found: 301.1776.
Compound 1: IR (neat): νmax = 1492, 1262, 1199, 814 cm-1. 1H NMR (300 MHz, CDCl3): δ = 6.86 (1 H, d, J = 8.1 Hz), 6.83 (1 H, s), 6.58 (1 H, d, J = 8.1 Hz), 2.50-2.14 (3 H, m), 2.25 (3 H, s), 2.10-1.90 (2 H, m), 1.65 (3 H, s), 1.14 (3 H, d, J = 6.6 Hz), 1.03 (3 H, d, J = 6.9 Hz). 13C NMR (75 MHz, CDCl3): δ = 150.1 (C), 128.6 (C), 128.5 (C), 128.4 (CH), 123.8 (CH), 116.1 (CH), 106.6 (C), 87.7 (C), 38.9 (CH2), 38.1 (CH2), 30.4 (CH), 24.3 (CH3), 21.0 (CH3), 18.6 (CH3), 16.8 (CH3). HRMS: m/z calcd for C15H20O2Na [M + Na]: 255.1361; found: 255.1359.
Bis-MOM ether 14: IR (neat): νmax = 1613, 1151, 1016, 923, 817 cm-1. 1H NMR (400 MHz, CDCl3): δ 7.30 (1 H, d, J = 8.0 Hz), 6.90 (1 H, s), 6.76 (1 H, d, J = 8.0 Hz), 5.73 (1 H, ddt, J = 16.8, 10.4, 6.4 Hz), 5.17 (2 H, s, OCH2O), 4.90 (1 H, d, J = 16.8 Hz), 4.84 (1 H, d, J = 10.4 Hz), 4.75 and 4.70 (2 H, 2 × d, J = 7.2 Hz), 3.47 (3 H, s), 3.41 (3 H, s), 2.32 (3 H, s), 2.20-1.90 (3 H, m), 1.86-1.70 (1 H, m), 1.68 (3 H, s). 13C NMR (100 MHz, CDCl3): δ = 154.3 (C), 139.1 (CH), 138.1 (C), 130.0 (C), 127.8 (CH), 122.0 (CH), 115.1 (CH), 113.8 (CH2), 93.9 (CH2), 91.6 (CH2), 80.3 (C), 56.0 (CH3), 55.4 (CH3), 39.1 (CH2), 28.7 (CH2), 24.7 (CH3), 21.2 (CH3). HRMS: m/z calcd for C17H26O4Na [M + Na]: 317.1729; found: 317.1717.
Ketone 17: IR (neat): νmax = 1711, 1613, 1150, 1015, 923, 817 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.30 (1 H, d, J = 7.9 Hz), 6.89 (1 H, s), 6.75 (1 H, d, J = 7.9 Hz), 5.15 (2 H, s), 4.73 and 4.71 (2 H, 2 × d, J = 7.2 Hz), 3.45 (3 H, s), 3.39 (3 H, s), 2.50-2.35 (3 H, m), 2.30 (3 H, s), 2.15-2.07 (2 H, m), 1.66 (3 H, s), 1.00 (3 H, d, J = 6.9 Hz), 0.95 (3 H, d, J = 6.9 Hz). 13C NMR (100 MHz, CDCl3): δ = 214.3 (C), 154.0 (C), 138.2 (C), 129.8 (C), 127.5 (CH), 121.9 (CH), 115.2 (CH), 94.0 (CH2), 91.4 (CH2), 79.8 (C), 56.0 (CH3), 55.4 (CH3), 40.8 (CH), 35.6 (CH2), 33.3 (CH2), 24.7 (CH3), 21.2 (CH3), 18.3 (CH3), 18.2 (CH3). HRMS: m/z calcd for C19H30O5Na [M + Na]: 361.1991; found: 361.1990.
Compound 2: IR (neat): νmax = 1624, 1303, 1160, 907, 802 cm-1. 1H NMR (400 MHz, CDCl3): δ = 6.89 (1 H, d, J = 7.9 Hz), 6.59 (1 H, d, J = 7.9 Hz), 6.56 (1 H, s), 2.26 (3 H, s), 2.20-2.08 (4 H, m), 1.90-1.83 (1 H, m), 1.69 (3 H, s), 1.09 (3 H, d, J = 6.7 Hz), 1.08 (3 H, d, J = 6.8 Hz). 13C NMR (100 MHz, CDCl3): δ = 151.5 (C), 138.2 (C), 126.5 (C), 122.6 (CH), 120.4 (CH), 116.4 (CH), 111.0 (C), 82.6 (C), 42.8 (CH2), 34.9 (CH2), 34.8 (CH), 21.8 (CH3), 21.2 (CH3), 17.0 (CH3), 16.8 (CH3). HRMS: m/z calcd for C15H20O2Na [M + Na]: 255.1361; found: 255.1364.
Compound 3: IR (neat): νmax = 1237, 911, 815 cm-1. 1H NMR (400 MHz, CDCl3): δ = 6.92 (1 H, d, J = 7.8 Hz), 6.84 (1 H, s), 6.63 (1 H, d, J = 7.8 Hz), 2.24 (3 H, s), 2.22-2.05 (4 H, m), 1.95-1.83 (1 H, m), 1.69 (3 H, s), 1.09 (3 H, d, J = 6.9 Hz), 1.07 (3 H, d, J = 6.9 Hz). 13C NMR (100 MHz, CDCl3): δ = 149.4 (C), 129.7 (C), 128.8 (CH), 128.7 (C), 123.4 (CH) 115.6 (CH), 111.1 (C), 82.7 (C), 42.7 (CH2), 34.7 (CH), 34.6 (CH2), 21.7 (CH3), 20.7 (CH3), 16.9 (CH3), 16.7 (CH3). HRMS: m/z calcd for C15H20O2Na [M + Na]: 255.1361; found: 255.1360.
Compound 4: IR (neat): νmax = 1624, 1386, 1167, 1078
cm-1. 1H NMR (400 MHz, CDCl3): δ = 6.95 (1 H, d, J = 8.0 Hz), 6.63 (1 H, d, J = 8.0 Hz), 6.56 (1 H, s), 2.25 (3 H, s), 2.60-2.20 (4 H, m), 2.10-1.90 (1 H, m), 1.66 (3 H, s), 1.13 (3 H, d, J = 6.9 Hz), 1.03 (3 H, d, J = 6.9 Hz). 13C NMR (100 MHz, CDCl3): δ = 152.2 (C), 137.9 (C), 126.0 (C), 123.3 (CH), 120.5 (CH) 116.8 (CH), 106.9 (C), 87.8 (C), 38.9 (CH2), 38.2 (CH2), 30.6 (CH), 24.2 (CH3), 21.1 (CH3), 18.5 (CH3), 16.8 (CH3). HRMS: m/z calcd for C15H20O2Na [M + Na]: 255.1361; found: 255.1359.

9

In the 1H NMR spectrum of the synthetic sample 2, it was found that signals due to four methyl groups and two aromatic protons were identical to those reported in the literature for the natural compound 2. Since one of the aromatic resonances (δ = 6.59 ppm, d) did not match that reported (δ = 6.89 ppm, d) for 2 [reported in the literature2 on the basis of the NMR spectrum of a 1:3 mixture (80% pure) of 2 and 1, where the compound 2 is minor component], the 1H NMR spectrum of a ca. 3:1 mixture of 1 and 2 was recorded and confirmed that the reported resonance at δ = 6.89 ppm is not due to 2. To rule out the other possible regioisomers completely, synthesis of compounds 3 and 4 were also accomplished5 starting from 2-hydroxy-5-methylacetophenones and 2-hydroxy-4-methylisobutyro-
phenones employing the same sequence of reactions as depicted in Schemes [1] and [3] , respectively. The 1H NMR and 13C NMR spectra5 of compounds 3 and 4 were found to be different from those reported in the literature2 for the compound 2 (Scheme [4] ).

Scheme 4