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(+)-14-HYDROXY-ISOSTEPHODELINE, a morphinan alkaloid from pachygone dasycarpa
\
Pergamon PII] S9920Ð8311"85#99753Ð2
Phytochemistry\ Vol[ 38\ No[ 7\ pp[ 1450Ð1452\ 0887 Þ 0887 Elsevier Science Ltd[ All rights reserved Printed in Great Britain 9920Ð8311:87:,*see front matter
"¦#!03!HYDROXY!ISOSTEPHODELINE\ A MORPHINAN ALKALOID FROM PACHYGONE DASYCARPA HEłLEŠNE GUINAUDEAU\ LONG!ZE LIN\% GEOFFREY A[ CORDELL and NIJSIRI RUANGRUNGSI$ Program for Collaborative Research in the Pharmaceutical Sciences\ Department of Medicinal Chemistry and Pharmacognosy\ College of Pharmacy\ University of Illinois at Chicago\ Chicago\ IL 59501\ U[S[A[^ $ Department of Pharmacognosy\ Faculty of Pharmaceutical Sciences\ Chulalongkorn University\ Bangkok\ Thailand "Received in revised form 03 November 0885#
Key Word Index*Pachy`one dasycarpa^ Menispermaceae^ Alkaloids^ Morphinan^ "¦#!03! hydroxy!isostephodeline[
Abstract*"¦#!03!Hydroxy!isostephodeline "0# is a new morphinan alkaloid isolated from the stem bark of Pachy`one dasycarpa\ a menispermaceous plant from Thailand[ Structure elucidation was achieved by the analysis of spectral data[ Þ0887 Elsevier Science Ltd[ All rights reserved
Pachy`one dasycarpa Kurz "Menispermaceae#\ a woody climber\ is known locally in Thai as {pok phaai| or {Yaa naang channg|[ The stem is used traditionally for its diuretic\ antinephritic\ antipyretic and anti! edema properties ð0Ł[ A study of the alkaloidal content of an extract of the stems bark has resulted in the isolation of numerous bisbenzylisoquinoline alkaloids ð1Ł\ an aporphine alkaloid\ "−#!anonaine\ and a new morphinan alkaloid\ "¦#!03!hydroxy!isostephodeline "0# whose structure elucidation is reported here[ "¦#!
Author to whom correspondence should be addressed^ alternative address] Faculty of Pharmacy\ 05 Boulevard Dav! iers\ 38934 Angers Cedex\ France[ % Present address] East Earth Herb Inc[\ 3980 W[ 00th Ave[\ Eugene\ OR 86391\ U[S[A[
03!Hydroxy!isostephodeline "0# possesses a mor! phinan alkaloid skeleton[ The EI!MS spectrum dis! plays a molecular ion at m:z 278 "69)# and a base peak at m:z 263[ This pattern is similar to that observed in the mass spectrum of other morphinans such as "¦#!isostephodeline "1# ð2Ł[ However\ the molecular ion and the base peak are 05 daltons higher than those of "¦#!isostephodeline "1#\ indicating that 0 bears an extra hydroxyl group[ The 0H NMR spectrum presents the characteristic signals of a morphinan molecule as observed in the spectrum of 1 "see Table 0#[ The chemical shift of the N!methyl signal is at d 1[30 ppm\ and four methyl singlets are observed at d 2[30\ 2[70\ 2[71 and 3[99 ppm[ Two one!proton singlets at d 5[30 and 5[50 ppm are\ respectively\ due to H!0 and H!3[ Two doublets at d 1[72 and 2[04 ppm "J 06[4 Hz# are due to the methylene group at C!4[ Instead of the usual CH1! CH!CH system observed for the protons at C!09\ C! 8 and C!03 in a morphinan type alkaloid ð2Ł\ a CH1! CH system is present at d 2[99 ppm "d\ Jgem 07[3 Hz#\ 1[80 ppm "dd\ Jgem 07[3 Hz\ Jvic 5[5 Hz#\ and 2[32 ppm "d\ Jvic 5[5 Hz#[ This suggests that C!03 is substituted and bears the hydroxyl group\ the presence of which is indicated by the mass spectrum[ Finally\ the methylene protons of C!04 and C!05 absorb as multiplets in the up_eld area of the spectrum at d 1[39 ppm "0H#\ 1[05 ppm "1H#\ and 0[22 ppm[ A signal at 080[2 ppm in the 02C NMR spectrum indicates the presence of a carbonyl group whose location was assigned through a ROESY experiment[ A correlation between the methoxyl singlet at d 3[99 ppm and the methylene protons of C!4 "d 1[72 and 2[04 ppm# indicates that C!5 bears a methoxyl group\ as in "¦#!isostephodeline "1# ð2Ł[ Therefore\ the car!
1450
1451
H[ GUINADEAU et al[ Table 0[ 0H and 02C NMR data of "¦#!03!hydroxy!isostephodeline "0# and "¦#!isostephodeline "1# in CDCl2
Carbon position 0 1 2 3 4
5 6 7 8 09
00 01 02 03 04 05 N!Me 1!OMe 2!OMe 5!OMe 6!OMe
"¦#!03!Hydroxy!isostephodeline "0#
"¦#!Isostephodeline "1# ð2Ł
0
02
0
02
5[40
009[3 036[8 036[8 095[4 23[2
5[41
009[6 036[4 036[2 095[3 28[4
H NMR
5[50 2[04 d 1[72 d "Jgem 06[4#
2[32 d J8[09 5[5 2[99 d 1[80 dd Jgem 07[3\ J8\09 5[5
* 1[05 m 0[22 m 1[39 m 1[05 m 1[30 2[70 2[71 3[99 2[30
C NMR
051[9 023[7 080[2 46[3 12[7
018[3 018[2 39[5 61[3 23[6 34[6 31[5 44[6 45[9 47[6 59[2
bonyl group is located at C!7[ This assignment was con_rmed by the chemical shift of C!4 "d 23[2 ppm\ determined by CSCM experiment# in the 02C NMR spectrum ð2Ł\ in the case of a C!5 carbonyl\ the chemi! cal shift of C!4 is around 36 ppm[ Complete assign! ments of the 0H and 02C NMR spectra were obtained by ROESY\ CSCM and selective INEPT experiments[ Comparison of the spectra of "¦#!03!hydroxy!iso! stephodeline "0# and "¦#!isostephodeline "1# con! _rmed the presence of a hydroxyl group at C!03[ Thus\ the C!03 resonance appears at d 42[2 ppm in the 02C NMR spectrum of "¦#!isostephodeline "1#\ whereas the chemical shift of the same carbon is 61[3 ppm for 0\ indicating substitution by an oxygenated group[ The C!02 signal "d 39[5 ppm# is also shifted down_eld by more than 09 ppm\ while the resonances of C!4 and C!04 are shifted up_eld by about 4 ppm[ The methoxyl at C!6 resonates at d 2[30 ppm which is characteristic of a B:C cis!fusion of rings B and C as in "¦#!isostephodeline "1# ð2Ł[ As "¦#!isostephodeline "1#\ "¦#!03!hydroxy!isostephodeline "0# is dextra! rotatory^ moreover the CD curves of 0 and 1 are very similar[ Therefore 0 and 1 possess the same absolute con_guration[ "¦#!03!Hydroxy!isostephodeline is the _rst natural morphinan bearing a hydroxyl at C!03[ Unfor!
H NMR
C NMR
5[52 2[00 d 1[57 d "Jgem 06[3#
2[55 m 1[76 dd 1[68 d Jgem 07[2\ J8\09 5[9
1[51 d 0[81 m 0[42 m 1[37 m 1[09 m 1[34 2[70 2[72 2[87 2[24
059[7 025[0 082[1 41[5 12[0
029[3 018[1 16[9 42[2 28[3 35[1
tunately\ the new morphinan did not show any anti! plasmodial activity as shown by the alkaloidal extract[ No cytotoxicity could be detected when the alkaloid was tested against a battery of cultures mammalian cells ð3Ł[ EXPERIMENTAL
General experimental procedures Optical rotations were measured with a PerkinÐ Elmer 130 polarimeter[ CD spectra were obtained with a JASCO J!609 spectropolarimeter[ NMR spec! tra] recorded with General Electric GE Omega 499 "0H and 02C NMR spectra and ROESY experiment#\ Nicolet NMC!259 "CSCM and selective INEPT experiments#\ and Varian XL!299 "APT spectrum# spectrometers in CDCl2 soln with TMS as int[ std[ EI!MS and HREI!MS were recorded on a Finnegan MAT!89 instrument[ All solvents were analytical grade or distilled prior to use[ Plant material[ Stems of Pachy`one dasycarpa were collected in MayÐJune 0882 from Erawan Waterfall\ Kanchanaburi Province\ Thailand[ Authentication was achieved by comparison with the herbarium speci! men at the Botany Section\ Technical Division\
A morphinan alkaloid from Pachy`one dasycarpa
Department of Agriculture\ Ministry of Agriculture and Cooperatives\ Thailand[ The herbarium specimen has been deposited in the Faculty of Pharmaceutical Sciences\ Chulalongkorn University\ Bangkok[
Extraction and isolation The dried powdered stem bark of Pachy`one dasy! carpa "4 kg# was macerated twice for a 2!day!period in EtOH and _ltered[ The combined _ltrate was evapd under reduced pressure to give a syrupy mass "119 g#[ The residue was treated with aq[ HCl "4)#\ the acidic soln was basi_ed with NH3OH to pH 8Ð09 and extracted with CHCl2[ Evapn of the organic solvent under reduced pressure a}orded the crude tertiary alkaloids "03[2 g#[ The aq soln containing quaternary alkaloids was treated with concentrated Mayers| reagent[ The ppt was dried and stored[ The tertiary alkaloid extract was passed through a column of silica gel 59 "Merck\ 69!129 mesh ASTM#[ Elution was con! ducted with CHCl2 gradually enriched with MeOH[ Further puri_cation was obtained by CC using silica gel 59 for TLC "Merk# with CHCl2ÐC5H01ÐMeOHÐ NH3OH "69]19]7]0# as solvent followed by prep TLC "Merk pre!coated TLC plates silica gel 59 F!143\ 9[14 cm# with acetonitrileÐEtOAcÐC5H5Ðdiethylamine "3]1]2]0#[ The _nal puri_cation furnished 0 "10 mg# as an amorphous powder[ "¦#!03!Hydroxy!isostephodeline "0#[ ðaŁD¦046> MeOH "MeOH\ c 9[052#^ UV lmax "log o# 193 "3[59#\ 115sh "3[93#\ 168 "2[85#\ CD MeOH\ Do "l nm# 9 "252#\ ¦19 "294#\ 9 "178#\ −13 "165#\ −3[2 "141sh#\ 9 "126#\ ¦0[5 "120#\ 9 "104#\ negative tail^ HREIMS 278[07246 "calc[
1452
for C10H16NO5] 278[07272#^ EI!MS m:z 289 "07#\ 278 "69#\ 264 "13#\ 263 "099#\ 261 "8#\ 247 "3#\ 245 "5#\ 150 "09#\ 107 "09#\ 195 "7#^ Selective INEPT experiment enhancements] H!0 to C!2^ OMe!1 to C!1^ OMe!2 to C!2^ H!3 to C!3\ C!1\ C!00\ and C!02^ H!4a to C!02\ C!03\ and C!6^ H!4b to C!01\ C!02\ C!03\ and C!5^ OMe!5 to C!5^ OMe!6 to C!6^ H!8 to C!03^ N!Me to C!8^ "¦#!Isostephodeline "1#[ CD] MeOH\ Do "l nm# 9 "289#\ ¦08 "290#\ 9 "176#\ −16 "163#\ −0 "140sh#\ 9 "136#\ ¦09 "116#\ 9 "100#\ negative tail[ Assays of antimalarial activity[ See ref[ ð3Ł[ Cell lines for cytotoxicity assays and evaluation of cytotoxic potential[ See ref[ ð3Ł[ Acknowled`ements*The authors would like to thank the Research Resources Center\ UIC\ for the pro! vision of NMR Spectroscopic facilities\ and Dr J[ M[ Pezzuto and Dr C[ K[ Angerhofer of the Bioassay Research Facility for the biological data[ REFERENCES
0[ Pongboonrod\ S[\ Mai Thet Muan` Thai[ Kasem! bunnakich Press\ Bangkok\ 0868\ p[ 312[ 1[ Guinaudeau\ H[\ Bohlke\ M[\ Lin\ L[!Z[\ Cordell\ G[ A[ and Ruangrungsi\ N[\ Journal of Natural Products\ 0886\ 59\ 147[ 2[ Charles\ B[\ Guinaudeau\ H[\ Bruneton\ J[ and Cabalion\ P[\ Canadian Journal of Chemistry\ 0878\ 56\ 0146[ 3[ Likhitwitaywuid\ K[\ Angerhofer\ C[ K[\ Cordell\ G[ A[ and Pezzuto\ J[ M[\ Journal of Natural Pro! ducts\ 0882\ 45\ 29[
Pergamon PII] S9920Ð8311"85#99753Ð2
Phytochemistry\ Vol[ 38\ No[ 7\ pp[ 1450Ð1452\ 0887 Þ 0887 Elsevier Science Ltd[ All rights reserved Printed in Great Britain 9920Ð8311:87:,*see front matter
"¦#!03!HYDROXY!ISOSTEPHODELINE\ A MORPHINAN ALKALOID FROM PACHYGONE DASYCARPA HEłLEŠNE GUINAUDEAU\ LONG!ZE LIN\% GEOFFREY A[ CORDELL and NIJSIRI RUANGRUNGSI$ Program for Collaborative Research in the Pharmaceutical Sciences\ Department of Medicinal Chemistry and Pharmacognosy\ College of Pharmacy\ University of Illinois at Chicago\ Chicago\ IL 59501\ U[S[A[^ $ Department of Pharmacognosy\ Faculty of Pharmaceutical Sciences\ Chulalongkorn University\ Bangkok\ Thailand "Received in revised form 03 November 0885#
Key Word Index*Pachy`one dasycarpa^ Menispermaceae^ Alkaloids^ Morphinan^ "¦#!03! hydroxy!isostephodeline[
Abstract*"¦#!03!Hydroxy!isostephodeline "0# is a new morphinan alkaloid isolated from the stem bark of Pachy`one dasycarpa\ a menispermaceous plant from Thailand[ Structure elucidation was achieved by the analysis of spectral data[ Þ0887 Elsevier Science Ltd[ All rights reserved
Pachy`one dasycarpa Kurz "Menispermaceae#\ a woody climber\ is known locally in Thai as {pok phaai| or {Yaa naang channg|[ The stem is used traditionally for its diuretic\ antinephritic\ antipyretic and anti! edema properties ð0Ł[ A study of the alkaloidal content of an extract of the stems bark has resulted in the isolation of numerous bisbenzylisoquinoline alkaloids ð1Ł\ an aporphine alkaloid\ "−#!anonaine\ and a new morphinan alkaloid\ "¦#!03!hydroxy!isostephodeline "0# whose structure elucidation is reported here[ "¦#!
Author to whom correspondence should be addressed^ alternative address] Faculty of Pharmacy\ 05 Boulevard Dav! iers\ 38934 Angers Cedex\ France[ % Present address] East Earth Herb Inc[\ 3980 W[ 00th Ave[\ Eugene\ OR 86391\ U[S[A[
03!Hydroxy!isostephodeline "0# possesses a mor! phinan alkaloid skeleton[ The EI!MS spectrum dis! plays a molecular ion at m:z 278 "69)# and a base peak at m:z 263[ This pattern is similar to that observed in the mass spectrum of other morphinans such as "¦#!isostephodeline "1# ð2Ł[ However\ the molecular ion and the base peak are 05 daltons higher than those of "¦#!isostephodeline "1#\ indicating that 0 bears an extra hydroxyl group[ The 0H NMR spectrum presents the characteristic signals of a morphinan molecule as observed in the spectrum of 1 "see Table 0#[ The chemical shift of the N!methyl signal is at d 1[30 ppm\ and four methyl singlets are observed at d 2[30\ 2[70\ 2[71 and 3[99 ppm[ Two one!proton singlets at d 5[30 and 5[50 ppm are\ respectively\ due to H!0 and H!3[ Two doublets at d 1[72 and 2[04 ppm "J 06[4 Hz# are due to the methylene group at C!4[ Instead of the usual CH1! CH!CH system observed for the protons at C!09\ C! 8 and C!03 in a morphinan type alkaloid ð2Ł\ a CH1! CH system is present at d 2[99 ppm "d\ Jgem 07[3 Hz#\ 1[80 ppm "dd\ Jgem 07[3 Hz\ Jvic 5[5 Hz#\ and 2[32 ppm "d\ Jvic 5[5 Hz#[ This suggests that C!03 is substituted and bears the hydroxyl group\ the presence of which is indicated by the mass spectrum[ Finally\ the methylene protons of C!04 and C!05 absorb as multiplets in the up_eld area of the spectrum at d 1[39 ppm "0H#\ 1[05 ppm "1H#\ and 0[22 ppm[ A signal at 080[2 ppm in the 02C NMR spectrum indicates the presence of a carbonyl group whose location was assigned through a ROESY experiment[ A correlation between the methoxyl singlet at d 3[99 ppm and the methylene protons of C!4 "d 1[72 and 2[04 ppm# indicates that C!5 bears a methoxyl group\ as in "¦#!isostephodeline "1# ð2Ł[ Therefore\ the car!
1450
1451
H[ GUINADEAU et al[ Table 0[ 0H and 02C NMR data of "¦#!03!hydroxy!isostephodeline "0# and "¦#!isostephodeline "1# in CDCl2
Carbon position 0 1 2 3 4
5 6 7 8 09
00 01 02 03 04 05 N!Me 1!OMe 2!OMe 5!OMe 6!OMe
"¦#!03!Hydroxy!isostephodeline "0#
"¦#!Isostephodeline "1# ð2Ł
0
02
0
02
5[40
009[3 036[8 036[8 095[4 23[2
5[41
009[6 036[4 036[2 095[3 28[4
H NMR
5[50 2[04 d 1[72 d "Jgem 06[4#
2[32 d J8[09 5[5 2[99 d 1[80 dd Jgem 07[3\ J8\09 5[5
* 1[05 m 0[22 m 1[39 m 1[05 m 1[30 2[70 2[71 3[99 2[30
C NMR
051[9 023[7 080[2 46[3 12[7
018[3 018[2 39[5 61[3 23[6 34[6 31[5 44[6 45[9 47[6 59[2
bonyl group is located at C!7[ This assignment was con_rmed by the chemical shift of C!4 "d 23[2 ppm\ determined by CSCM experiment# in the 02C NMR spectrum ð2Ł\ in the case of a C!5 carbonyl\ the chemi! cal shift of C!4 is around 36 ppm[ Complete assign! ments of the 0H and 02C NMR spectra were obtained by ROESY\ CSCM and selective INEPT experiments[ Comparison of the spectra of "¦#!03!hydroxy!iso! stephodeline "0# and "¦#!isostephodeline "1# con! _rmed the presence of a hydroxyl group at C!03[ Thus\ the C!03 resonance appears at d 42[2 ppm in the 02C NMR spectrum of "¦#!isostephodeline "1#\ whereas the chemical shift of the same carbon is 61[3 ppm for 0\ indicating substitution by an oxygenated group[ The C!02 signal "d 39[5 ppm# is also shifted down_eld by more than 09 ppm\ while the resonances of C!4 and C!04 are shifted up_eld by about 4 ppm[ The methoxyl at C!6 resonates at d 2[30 ppm which is characteristic of a B:C cis!fusion of rings B and C as in "¦#!isostephodeline "1# ð2Ł[ As "¦#!isostephodeline "1#\ "¦#!03!hydroxy!isostephodeline "0# is dextra! rotatory^ moreover the CD curves of 0 and 1 are very similar[ Therefore 0 and 1 possess the same absolute con_guration[ "¦#!03!Hydroxy!isostephodeline is the _rst natural morphinan bearing a hydroxyl at C!03[ Unfor!
H NMR
C NMR
5[52 2[00 d 1[57 d "Jgem 06[3#
2[55 m 1[76 dd 1[68 d Jgem 07[2\ J8\09 5[9
1[51 d 0[81 m 0[42 m 1[37 m 1[09 m 1[34 2[70 2[72 2[87 2[24
059[7 025[0 082[1 41[5 12[0
029[3 018[1 16[9 42[2 28[3 35[1
tunately\ the new morphinan did not show any anti! plasmodial activity as shown by the alkaloidal extract[ No cytotoxicity could be detected when the alkaloid was tested against a battery of cultures mammalian cells ð3Ł[ EXPERIMENTAL
General experimental procedures Optical rotations were measured with a PerkinÐ Elmer 130 polarimeter[ CD spectra were obtained with a JASCO J!609 spectropolarimeter[ NMR spec! tra] recorded with General Electric GE Omega 499 "0H and 02C NMR spectra and ROESY experiment#\ Nicolet NMC!259 "CSCM and selective INEPT experiments#\ and Varian XL!299 "APT spectrum# spectrometers in CDCl2 soln with TMS as int[ std[ EI!MS and HREI!MS were recorded on a Finnegan MAT!89 instrument[ All solvents were analytical grade or distilled prior to use[ Plant material[ Stems of Pachy`one dasycarpa were collected in MayÐJune 0882 from Erawan Waterfall\ Kanchanaburi Province\ Thailand[ Authentication was achieved by comparison with the herbarium speci! men at the Botany Section\ Technical Division\
A morphinan alkaloid from Pachy`one dasycarpa
Department of Agriculture\ Ministry of Agriculture and Cooperatives\ Thailand[ The herbarium specimen has been deposited in the Faculty of Pharmaceutical Sciences\ Chulalongkorn University\ Bangkok[
Extraction and isolation The dried powdered stem bark of Pachy`one dasy! carpa "4 kg# was macerated twice for a 2!day!period in EtOH and _ltered[ The combined _ltrate was evapd under reduced pressure to give a syrupy mass "119 g#[ The residue was treated with aq[ HCl "4)#\ the acidic soln was basi_ed with NH3OH to pH 8Ð09 and extracted with CHCl2[ Evapn of the organic solvent under reduced pressure a}orded the crude tertiary alkaloids "03[2 g#[ The aq soln containing quaternary alkaloids was treated with concentrated Mayers| reagent[ The ppt was dried and stored[ The tertiary alkaloid extract was passed through a column of silica gel 59 "Merck\ 69!129 mesh ASTM#[ Elution was con! ducted with CHCl2 gradually enriched with MeOH[ Further puri_cation was obtained by CC using silica gel 59 for TLC "Merk# with CHCl2ÐC5H01ÐMeOHÐ NH3OH "69]19]7]0# as solvent followed by prep TLC "Merk pre!coated TLC plates silica gel 59 F!143\ 9[14 cm# with acetonitrileÐEtOAcÐC5H5Ðdiethylamine "3]1]2]0#[ The _nal puri_cation furnished 0 "10 mg# as an amorphous powder[ "¦#!03!Hydroxy!isostephodeline "0#[ ðaŁD¦046> MeOH "MeOH\ c 9[052#^ UV lmax "log o# 193 "3[59#\ 115sh "3[93#\ 168 "2[85#\ CD MeOH\ Do "l nm# 9 "252#\ ¦19 "294#\ 9 "178#\ −13 "165#\ −3[2 "141sh#\ 9 "126#\ ¦0[5 "120#\ 9 "104#\ negative tail^ HREIMS 278[07246 "calc[
1452
for C10H16NO5] 278[07272#^ EI!MS m:z 289 "07#\ 278 "69#\ 264 "13#\ 263 "099#\ 261 "8#\ 247 "3#\ 245 "5#\ 150 "09#\ 107 "09#\ 195 "7#^ Selective INEPT experiment enhancements] H!0 to C!2^ OMe!1 to C!1^ OMe!2 to C!2^ H!3 to C!3\ C!1\ C!00\ and C!02^ H!4a to C!02\ C!03\ and C!6^ H!4b to C!01\ C!02\ C!03\ and C!5^ OMe!5 to C!5^ OMe!6 to C!6^ H!8 to C!03^ N!Me to C!8^ "¦#!Isostephodeline "1#[ CD] MeOH\ Do "l nm# 9 "289#\ ¦08 "290#\ 9 "176#\ −16 "163#\ −0 "140sh#\ 9 "136#\ ¦09 "116#\ 9 "100#\ negative tail[ Assays of antimalarial activity[ See ref[ ð3Ł[ Cell lines for cytotoxicity assays and evaluation of cytotoxic potential[ See ref[ ð3Ł[ Acknowled`ements*The authors would like to thank the Research Resources Center\ UIC\ for the pro! vision of NMR Spectroscopic facilities\ and Dr J[ M[ Pezzuto and Dr C[ K[ Angerhofer of the Bioassay Research Facility for the biological data[ REFERENCES
0[ Pongboonrod\ S[\ Mai Thet Muan` Thai[ Kasem! bunnakich Press\ Bangkok\ 0868\ p[ 312[ 1[ Guinaudeau\ H[\ Bohlke\ M[\ Lin\ L[!Z[\ Cordell\ G[ A[ and Ruangrungsi\ N[\ Journal of Natural Products\ 0886\ 59\ 147[ 2[ Charles\ B[\ Guinaudeau\ H[\ Bruneton\ J[ and Cabalion\ P[\ Canadian Journal of Chemistry\ 0878\ 56\ 0146[ 3[ Likhitwitaywuid\ K[\ Angerhofer\ C[ K[\ Cordell\ G[ A[ and Pezzuto\ J[ M[\ Journal of Natural Pro! ducts\ 0882\ 45\ 29[