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Bio-active monoterpenes from red seaweeds
0031-9422/84 $300+000 PergamonPressLtd
Phytochemlstry, Vol 23,No 7, pp 1449-1451, 1984 Pnntedm GreatBntam
BIO-ACTIVE MONOTERPENES PHILLIP CREWS, BARBARA L
FROM RED SEAWEEDS
MYERS, STEPHEN NAYLOR, ELISE L CLASON*, ROBERT S JACOBS*, GERARDUS STAALt
B
Thlmann Laboratones and Center for Coastal Manne Studies, Umverslty of Cahfomm, Santa Crux, CA 95064, U S A, *Marme Science Institute, Umverslty of Cahfomla, Santa Barbara, CA 93106, U S A, t Zoecon Corporation, Palo Alto, CA 94304, U S A (Rettsed recewed 29 December 1983) Key Word 1adex-Chondrococcu.s hornemmm, Plocanuaceae, Rhodophyceae, red seaweed, monoterpenes, ochtodane, biotoxlclty
Abstract-A reported
new ochtodane from Chondrococcus hornemanrz and the blotoxoclty of other seaweed monoterpenes
INTRODUcTION
IS
Compounds m the fourth skeletal fanuly (eg ochtodanes or l-ethyl-3,3-dimethylcyclohexanes) became avadable as a result of our recent field work m Tahiti A collection of Chondrococcus hornemantu yielded ochtodene (7) [3, 43, along with two new compounds 1,2dlchloro-ochtod-3,4-ene (8) and unpure epl-l,Zdlchloroochtod-3,4-ene (9) These were characterzed by spectroscop~c data Especmlly useful were “C NMR data, mcludmg APT and INEPT [8,9, Myers, B L , Loo, J , Ball, D and Crews, P., unpubhshed] We completely assigned the 13C NMR shifts m 7 [3] (see structures) based upon extensive SFORD Also, careful scrutmy of the ‘H NMR data for 7 showed a long range coupling J+ s = 2 Hz and this, along with “C NMR methyl shifts at 6 20 4and 28 9, were consistent with the assigned C-8 relative stereochemistry% The equatollal Cs-Br m 8 (CIOH14BrC13, [M]’ at m/z 318, 320, 322, 324) was assigned by a “CNMR SFORD correlation of the proton at 64 56 (dd, J = 10 8, 7 2 Hz) to the carbon at 654 3 (d) The chemical shift of the latter vs models clearly indicates Br rather than Cl at C-6 An axial Cl at C-8 was also evident based upon the 13C NMR methyl slufts vs models [ 141 l] Compound 9 could not be completely puked, but It was isolated m HPLC fractions accompanied by 8 That these two were epunenc at C-2 was clearly evident by comparmg then “CNMR chenucal stits Wtth these data as a precedent, we believe that halogen regmchemlstry m 10, which appears to be uncertam [12-141 at C-6 and C-8, can now be confidently assigned as shown here The new ochtodane 8 shows biotoxlclty m the antlcell dlvrsion assay as summamed in Table 2 However, ochtodene 7 did not show activity m spite of its previously observed lcthyotoxlclty [3]
Resultsaccumulated to date show that red seaweeds from the fanuhes Plocamlaceae and Rhlzophylhdaceae produce numerous halogenated monoterpenes which are divided into Just four carbon skeletal types [l] Both crude extracts and mdlvldual compounds from such seaweeds are often of interest because of their vaned hologcal activity ms has ranged from lchthyotoxrclty [2, 33, to fish antlfeedant [3], antlmlcroblal [4, 51 and antifungal [6] activities We Hrlsh to describe further examples of pronotmced bloactlvlty for these simple seaweed halogenated monoterpenes In addition we now report the isolation of a new ochtodane from Chondrococcus hornemannr RESULTS AND DlSCUSSlON The toxicity of Plocanuaceae crude extracts on goldfish ongmally prompted us to explore its chenustry [7] Interestingly, these crude extracts also show, at low concentrations, anti-insect activity, as sm in Table 1 Punfied metabohtes including compounds 1-Q which are nqor components from Plocamwn cartdagrneum or P vlolaceum, also show slgmficant anti-insect activity (Table 1) and are probably responsible for the biotoxlaty of the crude extracts Moreover, the actlvlty levels, especmlly mhlbltlon of mosquito larvae emergence, are comparable to those of commercial products It should also be noted that l-6 represent three of the known monoterpene skeleton types mcludmg 2,6-dlmethyloctanes, 1-ethyl-1,3&nethylLyclohexanes and lethyl-2,4-dlmethylcyclohexanes These same pure compounds (l-6) were next subJected to model pharmacolo@cal assays The results recorded m Table 2 show that compounds 2 and 6 exhlblt the most stgnficant activity levels
EXPERIMENTAL Our
SCornpounds l-6 are well known and are not illustrated $The followmg shifts (ppm) are predIcted for a XHX- m a C(6)HX-C(Me)2-C(8)HX army where X = Br C-6 = 55, C-8 = 56, X = Cl C-6 = 63, C-8 = 64-69 [l l]
general a&y&d, chenucal and chromatographlc methods have been described previously [lo] NMR spectra were recorded on a JEOL FX-100 PFT spectrometer operatmg at 25 0 MHz for “C and 100 MHz for ‘H Additional ‘“C NMR spectra at 75 MHz were recorded at Syntex and ‘H NMR spectra at 360 MHz were recorded at the Stanford Magnetic Resonance Lab (SMRL) Mass spectra were obtamed by chrectinlet at 20 eV
1449
1450
P CREWSet al Table 1 Ant]-insect activity agamst insect-senslfive synchromzed mstars* Hellothls
Manduca
tobacco hornworm larva-III Ocg/larva) LDSO
Aedes
Musca
mosqutto larvae (ppm) EC-SO
flY larvae Octiprepupa) ED-SO
tobacco budworm larva-III Ocg/larva) ED-SO
Crude extracts P cartdagmeum P vlolaceum P oregonum
Natural productst Cartilagmeal (1) 7-Bromochloromethyl-3,4,8tnchloro-3-methyl-1,5,7-octa-tnene (2) Vlolacene (3) Plocamene B (4) Plocamene D (5) Plocamene E (6) Standards Benzene hexachlorlde Methoprene Padan Permethrm Testmg threshold3
-
-
> 100 28 > 100
>lO >lO
> 100
-
> 100
>Ol
> loo
> loo
> 100 24 > 100 > loo > 100
>lO 005 >lO >Ol
30 65 -
> 100 32 -
> 100 > 100
> loo -
> 100 > 100 220 0 029 100
0 14 oooo2 041 -
003 0004 10 035 100
43 > 100 > 10 0018 100
00054
10
92
50
*ED-50 or EC-50 values are effective dose or concentration reqmred reduce metamorphosis to 50 ‘A,but m the case of methoprene ID-50 and K-50 values are c&d tFor chemical structures see 1, ref [7], 2, ref [lo], 36, ref [2], methoprene, ref [15] *Values greater than the testmg threshold mdlcate little or no actmty
7
8
CL
Tahiti (June 1982), extracted with CHZC12 munedlately after collection ylelded a crude 011 (0 848 g) Partitlonmg between hexane-MeOH (1 1) yielded semi-pure fractions 023Og (hexane), 0618 g (MeOH) ‘H NMR (360 MHz, benzene-d,) of the MeOH fraction revealed charactenstlc peaks for compounds 7-9 The MeOH fraction was subjected to flash chromatography (solvent gradlent of hexane to EtOAc) A total of five fractions were collected, and Fr 1 (hexane) and Fr 2 (hexane-EtOAc, 4 1) were combined (0 398 g) then SubJected to HPLC Ochtodene (7) HPLC fractions 15-20 gave 7 as a clear od (74 mg) with spectral proper&s and rotation [aD] = + 162” (c 0 065, CHCIs) matchmg those m the literature [3,4] An SFORD ‘H NMR at 6115 gave a sharp 13C peak at 628 8 1,2-Dtchloro-ochtod-3,4-enes (8 and 9) HPLC fractions 8 and 9 (14 mg) and 10-13 (82 mg) contamed respectively pure 8 and a mixture of 8 and 9 (ratlo of 5 1) Specdic physical propertles for 8 were [aD] = +50” (c 0045, CHCI,), ‘H NMR (360 MHz, CDCl,)S588(dd,J=54,36Hz,H-4),46O(t,J=72Hz,H-2), 4 56 (dd, J = 10 8,7 2 Hz, H&), 4 52 (s, H-Se), 3 95 (dd, J = 10 8, 7 2 Hz, H-l), 3 85 (dd, J = 10 8,7 2 Hz, H-l), 2 94 (add, J = 19 8, 7 2,5 4 Hz, H&z.), 2 69 (ddd, J = 19 8,10 8,3 6 Hz, H-5a), 130 (s,
with temperature programmmg, 100” for 1 mm followed by 3”/mm to 200” Rotations were measured on a Perkm Elmer polanmeter with a quartz mIcrocell (0 1 ml) Bloassays were camed out according to past procedures [15-171 The alga (60 14 g, dry wt), C hornemannz, from Bora Bora,
Me-lo), 1 10 (s, Me-9) Spm decoupling at 65 88 (H-4) revealed a clear ABX pattern at 62 69 (J = 3 6 Hz ehmmated), 2 94 (J = 5 4 Hz ehmmated) and 4 56 13C NMR (benzene-d,, 25 and 75 MHz) 134 4 (s, C-3), 1310 (d, C-4), 63 9 (d, C-S), 63 6 (d, C-2), 54 3 (d, C-6), 47 9 (t, C-l), 39 9 (s, C-7), 35 7 (t, C-5), 27 9 (q, C-lo), 19 7 (q, C-9) SFORD at 75 MHz was used to assign C-6, mass spectrum, m/z 318,320,322,324 [Ml’, 283,285,287 [M-Cl]‘, 203, 205, 207 [M-Cl, -HBr]+, 169, 167 [M-Cl, -HBr,
bo-active monoterpenes from red seaweeds
1451
Table 2 F&lo-assayactivity with animal model preparations Gumea prg heart auncle contraction rate and force
Compound* Cartilagmeal (1) 7-Bromochloromethyl-3,4,8tnchloro-3-methyl-1,5-7octatnene (2) Violacene (3) Plocamene B (4)
No effect
Plocamene D (5) Plocamene E (6) Ochtodene (7) Dichloro-ochtodene
(8)
Frog heart ventricle contraction force
Sea urchin cell dwrslon mhibition
Guinea pig ileum agomst, antagomst, or potentiator
No effect
Weak lustamme antagonism 45 % Histamine antagonism 25 % Acetylchohne antagonism Agonist Acetylchohne potentiation Histamme potentiation No effect Acetylchohne antagonism Histamine antagonism
-
No effect
No effect
76%
Force + 50 % No effect
Mild effect Mild effect
No effect No effect
No effect
No effect
Force + 30 %
-21%
No effect No effect
No effect
Mild effect Mild effect
No effect
18%
-
*All dose concentrations = 16 pg/ml
-HCl]+ Specdic physIcal properties for 9 were ‘H NMR (360 MHz, CD’&) 6 5 78 (dd, J = 5 4, 3 6, H-4), 4 65 (t, J = 7 2 HZ, H-2), 4 51 (dd, J = 10 8,7 2 Hz, H&), 4 45 (s, H-Se), 389(dd,J=108,72Hz,H-1),375(dd,J=108,72Hz,H-l), 294(ddd,J=198,72,54Hz,H-5a),125andlll(s,s,Me-9 and lo), “C NMR (25 and 75 MHZ, benzene&) 6 134 6 (s, C-3), 127 4 (d, C-4), 65 9 (d, C-2), 59 4 (d, C-S), 54 3 (d, C-6), 44 8 (t, C-l), 39 9 (s, C-7), 35 1 (t. C-5), 28 0 (q, C-lo), 19 9 (q, C-9)
2 Crews, P , Kho-Wiseman, E and Montana, P (1978) J Org Chem 43, 116 3 Paul, V J, McConnell, 0 J and Femcal, W (1980) J Org them. 45,340l 4 McConnell, 0 J and Femcal, W (1978) J Org Chem 43, 4238 5 Stalhud, M 0 and Faulkner, D J (1974) Camp &o&em Physlol 49B, 25
6 Stierle, D B , Wmg, R M and Suns, J J (1979) Tetrahedron 35,2855
Acknowledgements-Support for tlus research came from NOAA, National Sea Grant College Program, Department of Commerce, under University of Cahfomla Protect Numbers R/MP-24 (to PC) and R/MP-21 (to RSJ) The U S Government is author4 to produce and distnbute repnnts for governmental purposes We also thank the Sea Grant program for a trameeslllp to BLM Our field work m Tahiti was supported by a grant from the University Research Expeditions Program, and we thank MS J Colvm (program director) for her patient help We are grateful to Dr Michael Maddox for providing time on the HFX300 NMR spectrometer and to Dr James Jenson (UCSC) for the seaweed ldent&ation The 360 MHz NMR at SMRL IS sup ported by the National science Foundation (Grant No GR 23633) and the National Institutes of Health (Grant No RR 00711)
7 Crews, P and Kbo, E (1974) J Org Chem 39,3303 8 Patt, S L and Shoolery, J N (1982)J Magn Reson 46,535 9 Freeman, R and Moms, G A (1979) J Am Chem Sot 101, 760 10 Crews, P , Naylor, S , Hanke, F J , Hogue, E R , Kho, E and Bra&u, R J (1984) J Org Chem 49 (m press) 11 Crews, P and Kho-Wiseman, E (1978) Tetrahedron Letters 2483
12 Burreson, B J , Wollard, F X and Moore, R E (1975) Chem Letters 1111 13 Burreson, B J, Wollard, F X and Moore, R E (1975) Tetrahedron Letters 2155
14 Suns, J J, Rose, A F and Izac, R R (1978) m Marrne Natural Products Chernwry (Scheuer, P J , ed ) Vol 2, p 179 Acadenuc Press, New York 15 Hennck, C A, Wiley, W E and Staal, G B (1976) J Agnc Food Chem 24,207
REFERENCES 1 Naylor, S, Hanke, F J , Manes, L V and Crews, P (1983) Prog Chem Org Nat Prod 44, 189
16 Qmstad, G B, Cerf, D C, Schooley, D A and Staal, G B (1981) Nature 289, 176 17 Jacobs,R S, White,S and Wdson,L S (1981)Fed Proc 40, 26
Phytochemlstry, Vol 23,No 7, pp 1449-1451, 1984 Pnntedm GreatBntam
BIO-ACTIVE MONOTERPENES PHILLIP CREWS, BARBARA L
FROM RED SEAWEEDS
MYERS, STEPHEN NAYLOR, ELISE L CLASON*, ROBERT S JACOBS*, GERARDUS STAALt
B
Thlmann Laboratones and Center for Coastal Manne Studies, Umverslty of Cahfomm, Santa Crux, CA 95064, U S A, *Marme Science Institute, Umverslty of Cahfomla, Santa Barbara, CA 93106, U S A, t Zoecon Corporation, Palo Alto, CA 94304, U S A (Rettsed recewed 29 December 1983) Key Word 1adex-Chondrococcu.s hornemmm, Plocanuaceae, Rhodophyceae, red seaweed, monoterpenes, ochtodane, biotoxlclty
Abstract-A reported
new ochtodane from Chondrococcus hornemanrz and the blotoxoclty of other seaweed monoterpenes
INTRODUcTION
IS
Compounds m the fourth skeletal fanuly (eg ochtodanes or l-ethyl-3,3-dimethylcyclohexanes) became avadable as a result of our recent field work m Tahiti A collection of Chondrococcus hornemantu yielded ochtodene (7) [3, 43, along with two new compounds 1,2dlchloro-ochtod-3,4-ene (8) and unpure epl-l,Zdlchloroochtod-3,4-ene (9) These were characterzed by spectroscop~c data Especmlly useful were “C NMR data, mcludmg APT and INEPT [8,9, Myers, B L , Loo, J , Ball, D and Crews, P., unpubhshed] We completely assigned the 13C NMR shifts m 7 [3] (see structures) based upon extensive SFORD Also, careful scrutmy of the ‘H NMR data for 7 showed a long range coupling J+ s = 2 Hz and this, along with “C NMR methyl shifts at 6 20 4and 28 9, were consistent with the assigned C-8 relative stereochemistry% The equatollal Cs-Br m 8 (CIOH14BrC13, [M]’ at m/z 318, 320, 322, 324) was assigned by a “CNMR SFORD correlation of the proton at 64 56 (dd, J = 10 8, 7 2 Hz) to the carbon at 654 3 (d) The chemical shift of the latter vs models clearly indicates Br rather than Cl at C-6 An axial Cl at C-8 was also evident based upon the 13C NMR methyl slufts vs models [ 141 l] Compound 9 could not be completely puked, but It was isolated m HPLC fractions accompanied by 8 That these two were epunenc at C-2 was clearly evident by comparmg then “CNMR chenucal stits Wtth these data as a precedent, we believe that halogen regmchemlstry m 10, which appears to be uncertam [12-141 at C-6 and C-8, can now be confidently assigned as shown here The new ochtodane 8 shows biotoxlclty m the antlcell dlvrsion assay as summamed in Table 2 However, ochtodene 7 did not show activity m spite of its previously observed lcthyotoxlclty [3]
Resultsaccumulated to date show that red seaweeds from the fanuhes Plocamlaceae and Rhlzophylhdaceae produce numerous halogenated monoterpenes which are divided into Just four carbon skeletal types [l] Both crude extracts and mdlvldual compounds from such seaweeds are often of interest because of their vaned hologcal activity ms has ranged from lchthyotoxrclty [2, 33, to fish antlfeedant [3], antlmlcroblal [4, 51 and antifungal [6] activities We Hrlsh to describe further examples of pronotmced bloactlvlty for these simple seaweed halogenated monoterpenes In addition we now report the isolation of a new ochtodane from Chondrococcus hornemannr RESULTS AND DlSCUSSlON The toxicity of Plocanuaceae crude extracts on goldfish ongmally prompted us to explore its chenustry [7] Interestingly, these crude extracts also show, at low concentrations, anti-insect activity, as sm in Table 1 Punfied metabohtes including compounds 1-Q which are nqor components from Plocamwn cartdagrneum or P vlolaceum, also show slgmficant anti-insect activity (Table 1) and are probably responsible for the biotoxlaty of the crude extracts Moreover, the actlvlty levels, especmlly mhlbltlon of mosquito larvae emergence, are comparable to those of commercial products It should also be noted that l-6 represent three of the known monoterpene skeleton types mcludmg 2,6-dlmethyloctanes, 1-ethyl-1,3&nethylLyclohexanes and lethyl-2,4-dlmethylcyclohexanes These same pure compounds (l-6) were next subJected to model pharmacolo@cal assays The results recorded m Table 2 show that compounds 2 and 6 exhlblt the most stgnficant activity levels
EXPERIMENTAL Our
SCornpounds l-6 are well known and are not illustrated $The followmg shifts (ppm) are predIcted for a XHX- m a C(6)HX-C(Me)2-C(8)HX army where X = Br C-6 = 55, C-8 = 56, X = Cl C-6 = 63, C-8 = 64-69 [l l]
general a&y&d, chenucal and chromatographlc methods have been described previously [lo] NMR spectra were recorded on a JEOL FX-100 PFT spectrometer operatmg at 25 0 MHz for “C and 100 MHz for ‘H Additional ‘“C NMR spectra at 75 MHz were recorded at Syntex and ‘H NMR spectra at 360 MHz were recorded at the Stanford Magnetic Resonance Lab (SMRL) Mass spectra were obtamed by chrectinlet at 20 eV
1449
1450
P CREWSet al Table 1 Ant]-insect activity agamst insect-senslfive synchromzed mstars* Hellothls
Manduca
tobacco hornworm larva-III Ocg/larva) LDSO
Aedes
Musca
mosqutto larvae (ppm) EC-SO
flY larvae Octiprepupa) ED-SO
tobacco budworm larva-III Ocg/larva) ED-SO
Crude extracts P cartdagmeum P vlolaceum P oregonum
Natural productst Cartilagmeal (1) 7-Bromochloromethyl-3,4,8tnchloro-3-methyl-1,5,7-octa-tnene (2) Vlolacene (3) Plocamene B (4) Plocamene D (5) Plocamene E (6) Standards Benzene hexachlorlde Methoprene Padan Permethrm Testmg threshold3
-
-
> 100 28 > 100
>lO >lO
> 100
-
> 100
>Ol
> loo
> loo
> 100 24 > 100 > loo > 100
>lO 005 >lO >Ol
30 65 -
> 100 32 -
> 100 > 100
> loo -
> 100 > 100 220 0 029 100
0 14 oooo2 041 -
003 0004 10 035 100
43 > 100 > 10 0018 100
00054
10
92
50
*ED-50 or EC-50 values are effective dose or concentration reqmred reduce metamorphosis to 50 ‘A,but m the case of methoprene ID-50 and K-50 values are c&d tFor chemical structures see 1, ref [7], 2, ref [lo], 36, ref [2], methoprene, ref [15] *Values greater than the testmg threshold mdlcate little or no actmty
7
8
CL
Tahiti (June 1982), extracted with CHZC12 munedlately after collection ylelded a crude 011 (0 848 g) Partitlonmg between hexane-MeOH (1 1) yielded semi-pure fractions 023Og (hexane), 0618 g (MeOH) ‘H NMR (360 MHz, benzene-d,) of the MeOH fraction revealed charactenstlc peaks for compounds 7-9 The MeOH fraction was subjected to flash chromatography (solvent gradlent of hexane to EtOAc) A total of five fractions were collected, and Fr 1 (hexane) and Fr 2 (hexane-EtOAc, 4 1) were combined (0 398 g) then SubJected to HPLC Ochtodene (7) HPLC fractions 15-20 gave 7 as a clear od (74 mg) with spectral proper&s and rotation [aD] = + 162” (c 0 065, CHCIs) matchmg those m the literature [3,4] An SFORD ‘H NMR at 6115 gave a sharp 13C peak at 628 8 1,2-Dtchloro-ochtod-3,4-enes (8 and 9) HPLC fractions 8 and 9 (14 mg) and 10-13 (82 mg) contamed respectively pure 8 and a mixture of 8 and 9 (ratlo of 5 1) Specdic physical propertles for 8 were [aD] = +50” (c 0045, CHCI,), ‘H NMR (360 MHz, CDCl,)S588(dd,J=54,36Hz,H-4),46O(t,J=72Hz,H-2), 4 56 (dd, J = 10 8,7 2 Hz, H&), 4 52 (s, H-Se), 3 95 (dd, J = 10 8, 7 2 Hz, H-l), 3 85 (dd, J = 10 8,7 2 Hz, H-l), 2 94 (add, J = 19 8, 7 2,5 4 Hz, H&z.), 2 69 (ddd, J = 19 8,10 8,3 6 Hz, H-5a), 130 (s,
with temperature programmmg, 100” for 1 mm followed by 3”/mm to 200” Rotations were measured on a Perkm Elmer polanmeter with a quartz mIcrocell (0 1 ml) Bloassays were camed out according to past procedures [15-171 The alga (60 14 g, dry wt), C hornemannz, from Bora Bora,
Me-lo), 1 10 (s, Me-9) Spm decoupling at 65 88 (H-4) revealed a clear ABX pattern at 62 69 (J = 3 6 Hz ehmmated), 2 94 (J = 5 4 Hz ehmmated) and 4 56 13C NMR (benzene-d,, 25 and 75 MHz) 134 4 (s, C-3), 1310 (d, C-4), 63 9 (d, C-S), 63 6 (d, C-2), 54 3 (d, C-6), 47 9 (t, C-l), 39 9 (s, C-7), 35 7 (t, C-5), 27 9 (q, C-lo), 19 7 (q, C-9) SFORD at 75 MHz was used to assign C-6, mass spectrum, m/z 318,320,322,324 [Ml’, 283,285,287 [M-Cl]‘, 203, 205, 207 [M-Cl, -HBr]+, 169, 167 [M-Cl, -HBr,
bo-active monoterpenes from red seaweeds
1451
Table 2 F&lo-assayactivity with animal model preparations Gumea prg heart auncle contraction rate and force
Compound* Cartilagmeal (1) 7-Bromochloromethyl-3,4,8tnchloro-3-methyl-1,5-7octatnene (2) Violacene (3) Plocamene B (4)
No effect
Plocamene D (5) Plocamene E (6) Ochtodene (7) Dichloro-ochtodene
(8)
Frog heart ventricle contraction force
Sea urchin cell dwrslon mhibition
Guinea pig ileum agomst, antagomst, or potentiator
No effect
Weak lustamme antagonism 45 % Histamine antagonism 25 % Acetylchohne antagonism Agonist Acetylchohne potentiation Histamme potentiation No effect Acetylchohne antagonism Histamine antagonism
-
No effect
No effect
76%
Force + 50 % No effect
Mild effect Mild effect
No effect No effect
No effect
No effect
Force + 30 %
-21%
No effect No effect
No effect
Mild effect Mild effect
No effect
18%
-
*All dose concentrations = 16 pg/ml
-HCl]+ Specdic physIcal properties for 9 were ‘H NMR (360 MHz, CD’&) 6 5 78 (dd, J = 5 4, 3 6, H-4), 4 65 (t, J = 7 2 HZ, H-2), 4 51 (dd, J = 10 8,7 2 Hz, H&), 4 45 (s, H-Se), 389(dd,J=108,72Hz,H-1),375(dd,J=108,72Hz,H-l), 294(ddd,J=198,72,54Hz,H-5a),125andlll(s,s,Me-9 and lo), “C NMR (25 and 75 MHZ, benzene&) 6 134 6 (s, C-3), 127 4 (d, C-4), 65 9 (d, C-2), 59 4 (d, C-S), 54 3 (d, C-6), 44 8 (t, C-l), 39 9 (s, C-7), 35 1 (t. C-5), 28 0 (q, C-lo), 19 9 (q, C-9)
2 Crews, P , Kho-Wiseman, E and Montana, P (1978) J Org Chem 43, 116 3 Paul, V J, McConnell, 0 J and Femcal, W (1980) J Org them. 45,340l 4 McConnell, 0 J and Femcal, W (1978) J Org Chem 43, 4238 5 Stalhud, M 0 and Faulkner, D J (1974) Camp &o&em Physlol 49B, 25
6 Stierle, D B , Wmg, R M and Suns, J J (1979) Tetrahedron 35,2855
Acknowledgements-Support for tlus research came from NOAA, National Sea Grant College Program, Department of Commerce, under University of Cahfomla Protect Numbers R/MP-24 (to PC) and R/MP-21 (to RSJ) The U S Government is author4 to produce and distnbute repnnts for governmental purposes We also thank the Sea Grant program for a trameeslllp to BLM Our field work m Tahiti was supported by a grant from the University Research Expeditions Program, and we thank MS J Colvm (program director) for her patient help We are grateful to Dr Michael Maddox for providing time on the HFX300 NMR spectrometer and to Dr James Jenson (UCSC) for the seaweed ldent&ation The 360 MHz NMR at SMRL IS sup ported by the National science Foundation (Grant No GR 23633) and the National Institutes of Health (Grant No RR 00711)
7 Crews, P and Kbo, E (1974) J Org Chem 39,3303 8 Patt, S L and Shoolery, J N (1982)J Magn Reson 46,535 9 Freeman, R and Moms, G A (1979) J Am Chem Sot 101, 760 10 Crews, P , Naylor, S , Hanke, F J , Hogue, E R , Kho, E and Bra&u, R J (1984) J Org Chem 49 (m press) 11 Crews, P and Kho-Wiseman, E (1978) Tetrahedron Letters 2483
12 Burreson, B J , Wollard, F X and Moore, R E (1975) Chem Letters 1111 13 Burreson, B J, Wollard, F X and Moore, R E (1975) Tetrahedron Letters 2155
14 Suns, J J, Rose, A F and Izac, R R (1978) m Marrne Natural Products Chernwry (Scheuer, P J , ed ) Vol 2, p 179 Acadenuc Press, New York 15 Hennck, C A, Wiley, W E and Staal, G B (1976) J Agnc Food Chem 24,207
REFERENCES 1 Naylor, S, Hanke, F J , Manes, L V and Crews, P (1983) Prog Chem Org Nat Prod 44, 189
16 Qmstad, G B, Cerf, D C, Schooley, D A and Staal, G B (1981) Nature 289, 176 17 Jacobs,R S, White,S and Wdson,L S (1981)Fed Proc 40, 26