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A diterpene from the marine brown alga Dictyota bartayresii
Phymchemistry.Vol. 31. No. 7, pp. 2541-2542, 1992 Printed in Great B&am.
0
003 I -9422p2 s5.00 + 0.00 1992 Pcrgamon Press Ltd
A DITERPENE FROM THE MARINE BROWN ALGA DICTYOTA BARTAYRESII GABRIELE
Department
M. K~NIG, ANTHONYD. WRIGHT, ROCKY DE NYS and OTTO STICHER
of Pharmacy,
Swiss Federal Institute of Technology
(ETH) Zurich, CH-8092, Ziirich, Switzerland
(Received18 November 1991) Key Word I&x-Dictyota
bartoyresii, Dictyotaceae; brown algae; diterpeneq 8p-hydroxypachydictyol A.
Abe&act-From the dichloromethane extract of the brown alga Dictyota bartayresii a new diterpene, 8/?-hydroxypachydictyol A, of the hydroazulenoid type has been isolated and characterized. The structure of the new compound was determined from spectroscopic data (‘H NMR, 13C NMR, MS, IR).
INTRODUffION
Brown algae of the family Dictyotaceae have been shown to be very good sources of interesting and biologically active natural products. In the last few years we have been concentrating some of our research efforts into the investigation of algae from this family found growing around Magnetic Island, Queensland, Australia Cl, 23. Continuation of this effort now leads us to report on a further sample from this geographic region, the brown alga Dictyota bartayresii Lamouraux.
Anovm
indicateNOE .s
RESULTS AND DISCUSSION
From the marine brown alga D. bartayresii we isolated and characterized a single new bicarbocyclic diterpene (l), belonging to the hydroazulenoid diterpene structural type. Compound 1 was found to have the molecular formula C,,H,,O, by mass spectrometry. Three of the five degrees of unsaturation implied by the molecular formula of 1 were accounted for by carbon-carbon double bonds [al12.1 (t), 124.0(d), 124.7(d), 131.7(s), 141.9(s), 147.7(s)]. Further, inspection of both the IR and ’ 3C NMR spectra1 data for 1 indicated that both of the oxygen atoms present were in the form of secondary hydroxyl functions [3420cm-I, 668.9 (d), 72.6 (d)]. From the ‘H-‘H and *H-l 3C (one bond, J = 136 Hz) COSY spectra of 1 it was possible to trace proton-proton couplings through the molecule in such a way as to establish the gross structure of 1 on the basis of these data alone. Thus, the protons of the C-16 and C-20 methyl groups [S 1.68 (s), 1.61 (s)] both showed long range coupling to the C-14 olefinic proton Ca5.12 (br t, 5=7.2 Hz)], which in turn coupled to both of the allylic methylene protons at C-13 [S 1.95 (m), 2.12 (m)]. The latter two protons showed a geminal coupling as well as vicinal couplings to the two protons at C- 12 [a 1.34 (m), 1.68 (m)], which further coupled to the C-11 methine proton [S 1.94 (m)]. The proton with resonance at 6 1.94 further coupled to the protons of the C-19 secondary methyl group Cdl.12 (d, J=7.0 Hz)] and to the C-7 methine proton C61.53 (m)]. The C-7 proton in turn coupled to both of the protons attached to the carbons
1
bearing hydroxyl functions, H-6 Ca4.07 (m)], H-8 Ca4.10 (m)]. H-8 further coupled to the protons with resonances at 62.37 (dd, J=3.6, 14.5 Hz) and 63.00 (br dd, 5=4.3, 14.5 Hz). The latter proton then had long range couplings to one of the C-18 exo-methylene protons Ca4.96 (br s)]. Both exo-methylene protons C64.86 (br s), 4.96 (br s)] long range coupled to the proton at C-l cS2.73 (m)], which in turn coupled to the protons of both the C-2 methylene C62.13 (m), 2.48 (m)] and the C-5 methine C62.53 (m)] groups. The proton of the C-5 methine group further coupled to the methine proton of the C-6 secondary alcohol, completing one of the two rings implied by the molecular formula of 1. The two methylene protons at C2, as well as coupling to the proton at C-l cS2.73 (m)], coupled to the C-3 olefinic proton C65.34 (br s)], which in turn showed long range coupling to the protons of the C17 methyl group. Clearly C-4 must then bond to C-5 giving rise to the second of the two rings implied by the molecular formula of 1.The basic structure of 1 contained six asymmetric centres and one double bond that required stereochemical assignment. The double bond was assigned as Z on the basis of literature precedents [3,4], and the fact that the E-configuration is virtually impossible to construct with Dreiding models. The six asymmetric centres were all assigned, with the exceptions of C-6
2541
2542
Short Reports
and C-l 1, the latter of which has no relative stereochemistry, from the results of a ZD-NOESY experiment performed with 1. The important and diagnostic NOES are illustrated in 1. The stereochemistry at C-6 was assigned on the basis of ‘H and “CNMR data comparisons made between I and a series of known compounds, dictyols, possessing the same functionality at C-6 [5 81. WC propose the non-systematic name of X/j’-hydroxypachydictyol A for 1. EXPERIMENTAL
Grnerul c.xpenmenrol procedures. See ref. [9]. PIant materiul. The plant material was obtained during July 1984 from Geoffrey Bay, Magnetic Island. Queensland, Australia. Plants growing at (r6 m depth were collected, deepfrozen and then freeze-dried. A museum specimen is deposited in the Department of Chemistry. James Cook University (voucher number mm IO). Extraction und isolarion. Deep frozen tissue was freeze-dried. Dry tissue (163 g) was extracted with CH,CI, (3 I) to afford 5.2 g (3.2%) of CH,Cl,-soluble material. Vacuum liquid chromatography (VLC) of the CH,CI, solubles over silica gel, using hexane containing Increasing proportions of EtOAc as eluent. afforded 21 fractions. HPLC separation of fraction 12, employing normal phase silica and hexane EtOAc (4: I) as eluent. yielded a single pure compound. I. 88-HL’dn)r~pach~di[.rJ.f~~ A (1). (I 6 mg, 0.01%) was obtained as a yellow oil with [z]c -22.0’ (CHCI,; ~0.20); IR v,,,cm -I: 3420,292O. 1710. 1640, 1450, 1375; ‘H NMR (300 MHz, CDCI,) 61.12(6. J=7.0 H7.3H. H-19). 1.34(m, IH, H-12). 1.53(m. IH, H7). 1.61 (s. 3H. H-20), 1.68 (5. 3H, H-16), 1.68 (m, IH, H-I?), 1.79 (brs.3H. H-17). 1.94(m. IH. H-II). 1.95(nt, IH. H-13). 2.12(m, 1H. H-13),2.13(m. IH,H-2),2.37(dd,J=3.6, 14.5 Hz, IH, H-9). 2.48(m. IH, H-2). 2.53(m, 1H. H-5).2.73(m. IH, H-l), 3.00(hrdd. J-4.3, 14.5Hz. lH.H-9),4.07(dd,J=2.6,6.5Hz. lH.H-6),4.10 (m,lH.H-8),4.86(hrs. lH.H-IX),4.96(hrs. IH.H-l8),5.l2(hrr. J-7.2 Hz. IH. H-14). 5.34(hr.s. IH. H-3); “CNMR(75.5 MHz.
CDCl,) 6 14.6 (4. C-17), 17.7 (q, C-20). 18.4 (q. C-19). 25.7 (q. Cl@, 26.6(r,C-13), 34.1 (d,C-I I), 35.6&C-12). 35.8(1.C-2),45.4(1. C-9), 47.4 (d. C-l), 52.0 (d, C-7), 58.3 (d. C-5). 68.9 (d, C-8). 72.6 (d, C-6), 112.1 (r,C-18). 124.0(d.C-3). 124.7(d.C-14). 131.7(s,C-15). 141.9 (s. C-4). 147.7 (s. C-IO); HREIMS, obsd, m/z 304.2398, C,,H,,O, requires 304.2408; EIMS. m,:z (rel. mt.): 304 [M] + (4). 286 (12). 26X (5). 253 (3). 225 (4). 186 (16). 173 (20). 157 (30). 135 (45). 121 (73). IO7 (87). 69 (100).
Aclino&dgements-We thank Dr Ian Price. Department of Botany. James Cook University, Townsville Q481 I, Australia, for species assignment; Dr E. Zass, ETH Chemistry Department, for performmg hterature searches and Mr Oswald Greter and Dr Walter Amrem, ETH Chemistry Department Mass Spectral Service. for recording all mass spectra and making accurate mass measurements.
REFERENCES I. Kanig.
G. M.. Wright. hedron 46. 3X5 I. 2. Kiinig, G M., Wright,
A. D. and Sticher,
0. (1990) T&a-
A. D. and Stlcher.
0. (1991) Tetra-
hedron 47, 1399.
3. Vazquez. J. T.. Chang, M., Nakamshi, K.. Manta E., Perez_ C. and Martin, J. D. (1988) J. Org. Chem. 53, 4797. 4. Hirschfcld, D. R.. Fenical, W.. Lin, G. H. Y., Wing, R. M., Radlick. P. and Sims, J. J. (1973) J. Am. Chem. Sot. 95.4049. A. G., Manta. E. and 5. Rivera. A. P.. Astudillo. L. A., Gonzalel Cataldo. F. (1987) J. .Var. Prod. 50. 965. C. and Anderson, R. J. (1984) Can. J. Chem. 62, 6. Pathirana. 1666. De Rosa, S., De Stefano. S. and Zavodnik. N. (1986) Phytochemisrr), 25, 2 179.
Alvarado. A. B and Gerwick, W. H. (1985) J. Not. Prod. 48, 132. Wright, A. D., Khnrg, G. M. and Sticher, 0. (1991) J. Nat. Prod. 54. 1025.
0
003 I -9422p2 s5.00 + 0.00 1992 Pcrgamon Press Ltd
A DITERPENE FROM THE MARINE BROWN ALGA DICTYOTA BARTAYRESII GABRIELE
Department
M. K~NIG, ANTHONYD. WRIGHT, ROCKY DE NYS and OTTO STICHER
of Pharmacy,
Swiss Federal Institute of Technology
(ETH) Zurich, CH-8092, Ziirich, Switzerland
(Received18 November 1991) Key Word I&x-Dictyota
bartoyresii, Dictyotaceae; brown algae; diterpeneq 8p-hydroxypachydictyol A.
Abe&act-From the dichloromethane extract of the brown alga Dictyota bartayresii a new diterpene, 8/?-hydroxypachydictyol A, of the hydroazulenoid type has been isolated and characterized. The structure of the new compound was determined from spectroscopic data (‘H NMR, 13C NMR, MS, IR).
INTRODUffION
Brown algae of the family Dictyotaceae have been shown to be very good sources of interesting and biologically active natural products. In the last few years we have been concentrating some of our research efforts into the investigation of algae from this family found growing around Magnetic Island, Queensland, Australia Cl, 23. Continuation of this effort now leads us to report on a further sample from this geographic region, the brown alga Dictyota bartayresii Lamouraux.
Anovm
indicateNOE .s
RESULTS AND DISCUSSION
From the marine brown alga D. bartayresii we isolated and characterized a single new bicarbocyclic diterpene (l), belonging to the hydroazulenoid diterpene structural type. Compound 1 was found to have the molecular formula C,,H,,O, by mass spectrometry. Three of the five degrees of unsaturation implied by the molecular formula of 1 were accounted for by carbon-carbon double bonds [al12.1 (t), 124.0(d), 124.7(d), 131.7(s), 141.9(s), 147.7(s)]. Further, inspection of both the IR and ’ 3C NMR spectra1 data for 1 indicated that both of the oxygen atoms present were in the form of secondary hydroxyl functions [3420cm-I, 668.9 (d), 72.6 (d)]. From the ‘H-‘H and *H-l 3C (one bond, J = 136 Hz) COSY spectra of 1 it was possible to trace proton-proton couplings through the molecule in such a way as to establish the gross structure of 1 on the basis of these data alone. Thus, the protons of the C-16 and C-20 methyl groups [S 1.68 (s), 1.61 (s)] both showed long range coupling to the C-14 olefinic proton Ca5.12 (br t, 5=7.2 Hz)], which in turn coupled to both of the allylic methylene protons at C-13 [S 1.95 (m), 2.12 (m)]. The latter two protons showed a geminal coupling as well as vicinal couplings to the two protons at C- 12 [a 1.34 (m), 1.68 (m)], which further coupled to the C-11 methine proton [S 1.94 (m)]. The proton with resonance at 6 1.94 further coupled to the protons of the C-19 secondary methyl group Cdl.12 (d, J=7.0 Hz)] and to the C-7 methine proton C61.53 (m)]. The C-7 proton in turn coupled to both of the protons attached to the carbons
1
bearing hydroxyl functions, H-6 Ca4.07 (m)], H-8 Ca4.10 (m)]. H-8 further coupled to the protons with resonances at 62.37 (dd, J=3.6, 14.5 Hz) and 63.00 (br dd, 5=4.3, 14.5 Hz). The latter proton then had long range couplings to one of the C-18 exo-methylene protons Ca4.96 (br s)]. Both exo-methylene protons C64.86 (br s), 4.96 (br s)] long range coupled to the proton at C-l cS2.73 (m)], which in turn coupled to the protons of both the C-2 methylene C62.13 (m), 2.48 (m)] and the C-5 methine C62.53 (m)] groups. The proton of the C-5 methine group further coupled to the methine proton of the C-6 secondary alcohol, completing one of the two rings implied by the molecular formula of 1. The two methylene protons at C2, as well as coupling to the proton at C-l cS2.73 (m)], coupled to the C-3 olefinic proton C65.34 (br s)], which in turn showed long range coupling to the protons of the C17 methyl group. Clearly C-4 must then bond to C-5 giving rise to the second of the two rings implied by the molecular formula of 1.The basic structure of 1 contained six asymmetric centres and one double bond that required stereochemical assignment. The double bond was assigned as Z on the basis of literature precedents [3,4], and the fact that the E-configuration is virtually impossible to construct with Dreiding models. The six asymmetric centres were all assigned, with the exceptions of C-6
2541
2542
Short Reports
and C-l 1, the latter of which has no relative stereochemistry, from the results of a ZD-NOESY experiment performed with 1. The important and diagnostic NOES are illustrated in 1. The stereochemistry at C-6 was assigned on the basis of ‘H and “CNMR data comparisons made between I and a series of known compounds, dictyols, possessing the same functionality at C-6 [5 81. WC propose the non-systematic name of X/j’-hydroxypachydictyol A for 1. EXPERIMENTAL
Grnerul c.xpenmenrol procedures. See ref. [9]. PIant materiul. The plant material was obtained during July 1984 from Geoffrey Bay, Magnetic Island. Queensland, Australia. Plants growing at (r6 m depth were collected, deepfrozen and then freeze-dried. A museum specimen is deposited in the Department of Chemistry. James Cook University (voucher number mm IO). Extraction und isolarion. Deep frozen tissue was freeze-dried. Dry tissue (163 g) was extracted with CH,CI, (3 I) to afford 5.2 g (3.2%) of CH,Cl,-soluble material. Vacuum liquid chromatography (VLC) of the CH,CI, solubles over silica gel, using hexane containing Increasing proportions of EtOAc as eluent. afforded 21 fractions. HPLC separation of fraction 12, employing normal phase silica and hexane EtOAc (4: I) as eluent. yielded a single pure compound. I. 88-HL’dn)r~pach~di[.rJ.f~~ A (1). (I 6 mg, 0.01%) was obtained as a yellow oil with [z]c -22.0’ (CHCI,; ~0.20); IR v,,,cm -I: 3420,292O. 1710. 1640, 1450, 1375; ‘H NMR (300 MHz, CDCI,) 61.12(6. J=7.0 H7.3H. H-19). 1.34(m, IH, H-12). 1.53(m. IH, H7). 1.61 (s. 3H. H-20), 1.68 (5. 3H, H-16), 1.68 (m, IH, H-I?), 1.79 (brs.3H. H-17). 1.94(m. IH. H-II). 1.95(nt, IH. H-13). 2.12(m, 1H. H-13),2.13(m. IH,H-2),2.37(dd,J=3.6, 14.5 Hz, IH, H-9). 2.48(m. IH, H-2). 2.53(m, 1H. H-5).2.73(m. IH, H-l), 3.00(hrdd. J-4.3, 14.5Hz. lH.H-9),4.07(dd,J=2.6,6.5Hz. lH.H-6),4.10 (m,lH.H-8),4.86(hrs. lH.H-IX),4.96(hrs. IH.H-l8),5.l2(hrr. J-7.2 Hz. IH. H-14). 5.34(hr.s. IH. H-3); “CNMR(75.5 MHz.
CDCl,) 6 14.6 (4. C-17), 17.7 (q, C-20). 18.4 (q. C-19). 25.7 (q. Cl@, 26.6(r,C-13), 34.1 (d,C-I I), 35.6&C-12). 35.8(1.C-2),45.4(1. C-9), 47.4 (d. C-l), 52.0 (d, C-7), 58.3 (d. C-5). 68.9 (d, C-8). 72.6 (d, C-6), 112.1 (r,C-18). 124.0(d.C-3). 124.7(d.C-14). 131.7(s,C-15). 141.9 (s. C-4). 147.7 (s. C-IO); HREIMS, obsd, m/z 304.2398, C,,H,,O, requires 304.2408; EIMS. m,:z (rel. mt.): 304 [M] + (4). 286 (12). 26X (5). 253 (3). 225 (4). 186 (16). 173 (20). 157 (30). 135 (45). 121 (73). IO7 (87). 69 (100).
Aclino&dgements-We thank Dr Ian Price. Department of Botany. James Cook University, Townsville Q481 I, Australia, for species assignment; Dr E. Zass, ETH Chemistry Department, for performmg hterature searches and Mr Oswald Greter and Dr Walter Amrem, ETH Chemistry Department Mass Spectral Service. for recording all mass spectra and making accurate mass measurements.
REFERENCES I. Kanig.
G. M.. Wright. hedron 46. 3X5 I. 2. Kiinig, G M., Wright,
A. D. and Sticher,
0. (1990) T&a-
A. D. and Stlcher.
0. (1991) Tetra-
hedron 47, 1399.
3. Vazquez. J. T.. Chang, M., Nakamshi, K.. Manta E., Perez_ C. and Martin, J. D. (1988) J. Org. Chem. 53, 4797. 4. Hirschfcld, D. R.. Fenical, W.. Lin, G. H. Y., Wing, R. M., Radlick. P. and Sims, J. J. (1973) J. Am. Chem. Sot. 95.4049. A. G., Manta. E. and 5. Rivera. A. P.. Astudillo. L. A., Gonzalel Cataldo. F. (1987) J. .Var. Prod. 50. 965. C. and Anderson, R. J. (1984) Can. J. Chem. 62, 6. Pathirana. 1666. De Rosa, S., De Stefano. S. and Zavodnik. N. (1986) Phytochemisrr), 25, 2 179.
Alvarado. A. B and Gerwick, W. H. (1985) J. Not. Prod. 48, 132. Wright, A. D., Khnrg, G. M. and Sticher, 0. (1991) J. Nat. Prod. 54. 1025.