Two chromenes from Evodia lepta

Article abstract of DOI:10.1016/S0031-9422(98)00122-8

Two new chromenes named, leptonol and methylleptol A, along with four known compounds, alloevodione, 7, 4-dihydroxy-3, 5, 3'-trimethoxyflavone, 3, 7-dimethylkaempferol and clovandiol have been isolated from Evodia lepta. Their structures were elucidated by spectroscopic analysis and chemical techniques.

Full text of DOI:10.1016/S0031-9422(98)00122-8

Phytochemistry\ Vol[ 37\ No[ 5\ pp[ 0940Ð0943\ 0887
Þ 0887 Elsevier Science Ltd[ All rights reserved
Printed in Great Britain
Pergamon
\
9920Ð8311:87 ,08[99¦9[99
PII] S9920Ð8311"87#99011Ð7
TWO CHROMENES FROM EVODIA LEPTA
GUO!LIN LI and DA!YUAN ZHU
State Key Laboratory of Drug Research of Shanghai Institute of Materia Medica\ Chinese Academy of Sciences\
Shanghai\ 199920 People|s Republic of China
"Received 4 January 0887#
Key Word Index*Evodia lepta^ Rutaceae^ chromenes^ leptonol^ methylleptol A^ alloevodione[
Abstract*Two new chromenes named\ leptonol and methylleptol A\ along with four known compounds\
alloevodione\ 6\ 3!dihydroxy!2\ 4\ 2?!trimethoxy~avone\ 2\ 6!dimethylkaempferol and clovandiol\ have been
isolated from Evodia lepta[ Their structures were elucidated by spectroscopic analysis and chemical techniques[
Þ 0887 Elsevier Science Ltd[ All rights reserved
INTRODUCTION
leptol A[ The IR spectrum demonstrated that this
compound had no hydroxyl group[ From the above
results\ we could infer methylleptol A was the product
of methylation of leptol A[ Methylation of leptol A
using methanol!formic acid method gave methylleptol
A\ and this con_rmed the above inference[ Thus\ the
structure of methylleptol A "1# was elucidated as 5!
"0?!methoxyethyl#!4\6\7!trimethoxy!1\1!dimethyl!1H!
ð0Ł!benzopyran[
Our previous study has resulted in the isolation and
structural elucidation of three new compounds "leptol
A\ ethylleptol A and leptene A# and two known com!
pounds "isoevodionol and evodione# ð0Ł from the tra!
ditional Chinese herb\ Evodia lepta[ As a part of our
continuing research into the same material\ we now
wish to report the isolation and structural elucidation
of two new chromenes\ leptonol "0# and methylleptol
A "1#\ and one known chromene\ alloevodione "2#[
Alloevodione "2# was isolated as pale yellow oil[ Its
0H NMR spectrum was almost identical to that of
evodione "0a# ð0Ł\ except for small chemical shift
di}erence[ They also had the same ðmŁ¦ and main
fragment ions peaks in their EI mass spectra ð0Ł[ These
data suggested that they had the same skeleton and
substituted groups\ but they were not the same
because they had di}erent TLCRf values[ "silica gel\
petrol!EtOAc\ 01]0#[ The di}erence in their structure
was the position of the acetyl group[ We cannot ident!
ify compound 2 as alloevodione\ which is a known
natural product from E[ elleyana ð3Ł\ without further
RESULTS AND DISCUSSION
0
Leptonol "0# was obtained as an orange oil[ Its H
NMR spectrum was very similar to that of evodione\
except that the hydroxyl signal "d 02[46# in compound
0 was substituted by that of methoxyl group[ Because
methylation of 0 using "CH2#1SO3ÐK1CO2!acetone ð1Ł
gave evodione "0a#\ the acetyl group in 0 was assigned
to position 5[ A chelated phenolic hydroxyl signal at d
02[46 in its 0H NMR spectrum and a chelated carbonyl
group absorption at 0539 cm−0 in its IR spectrum\
demonstrated that the hydroxyl group was at position
4 or 6[ Acetylation of 0 using acetic anhydride!pyri!
dine a}orded 0b[ The up_eld shift of H!3 "Ddꢀ9[31#
0
study\ because the H NMR spectrum of compound
2 was di}erent from that of alloevodione given in the
literature ð4Ł[ Reduction of 2 using NaBH3!MeOH
method gave compound 2a[ In the HMBC spectrum
of compound 2a\ H!3 was correlated with the carbons
at d 038[4 and 036[3\ respectively\ and the proton of
one methoxyl group at d 2[71 was also correlated with
the carbon at d 038[4[ This suggested that the carbon
at d 038[4 should be assigned to C!4 and the carbon
at d 036[3 should be assigned to C!8[ Because H!0?
was correlated with the carbons at d 036[3 "C!8#\ d
041[4 and d 012[3\ C!0? should be attached to C!7[
The carbon at d 041[4 should be assigned to C!6\ and
the carbon at d 012[3 to C!7[ Because compound 2a
0
in the H NMR spectrum after acetylation of 0 indi!
cated that the hydroxyl group was at position 4\
according to the rules of Arnone ð2Ł[ Thus\ leptonol
"0# was determined as 4!hydroxyl!5!acetyl!6\7!dime!
thoxy!1\1!dimethyl!1H!ð0Ł!benzopyran[
Methylleptol A "1# was colourless oil[ Its 0H NMR
spectrum showed the presence of a methoxyl group at
d 2[07 "2H\ s#^ other signals were similar to those of
leptol A\ a chromene from the same material ð0Ł[ The
EI mass spectrum of this compound indicated the was the product of reduction of compound 2\ the
ðmŁ¦ at m:z 297\ which was 03 mu more than that of acetyl group in compound 2a should be placed at
0940

0941
GUO!LIN LI AND DA!YUAN ZHU
position 7[ From above results\ compound 2 was
identi_ed as 4\ 5\ 6!trimethoxy!7!acetyl!1\ 1!dimethyl!
1Hð0Ł!benzopyran\ a known compound from E[
ellerya[
EXPERIMENTAL
General
EIMS] 69 eV\ direct inlet[ 0H NMR] 399 MHz\
Compounds 3\ 4\ and 5 were identi_ed as 6\ 3?! CDCl2 and CD2COCD2[ 02C NMR] 099 MHz\ CDCl2
dihydroxy!2\ 4\ 2?!trimethoxy~avone ð5Ł\ 2\ 6!dime! and CD2COCD2[ Chemical shifts are given in d and
thylkaempferol ð6Ł and clovandiol ð7Ł\ respectively\ by were referred in CDCl2 to the residual CHCl2 "d 6[13
comparison of their spectral data with those of the for 0H\ 66[9 for 02C# and in CD2COCD2 to the residual
corresponding compounds reported in the literature[
Me1CO "d 1[94 for 0H\ 18[7 for 02C#[

Two chromenes from Evodia lepta
0942
Plant material
Methylleptol A "1#
C06H13O4[ Colourless oil[ ðaŁ15Dꢀ ¦9[978>
Aerial parts of E[ lepta "Spreng# Merr[ were col!
lected from Hainan province\ P[ R[ China\ in July\ "CH2COCH2^ c 9[349#[ IR nfilmmax cm−0] 1879\ 1829\
0881[ A voucher sample "809931# is deposited in the 0639\ 0524\ 0482\ 0360\ 0264\ 0259\ 0083\ 0025\ 0942\
Herbarium of Shanghai Institute of Materia Medica\ 867[ 0H NMR "CD2COCD2#] d 5[43 "0H\ d\ Jꢀ8[7 Hz\
Chinese Academy of Sciences[ A specimen was auth! H!3#\ 4[62 "0H\ d\ Jꢀ8[7 Hz\ H!2#\ 3[60 "0H\ q\
enticated by Dr Xiao!qiang Ma\ Department of Phy! Jꢀ5[6 Hz\ H!0?#\ 2[70 "5H\ s\ 1×−OCH2#\ 2[58 "2H\
tochemistry\ Shanghai Institute of Materia Medica\ s\−OCH2#\ 2[07 "2H\ s\ H!0ý#\ 0[41 "2H\ d\ Jꢀ5[6 Hz\
Chinese Academy of Sciences[
H!1?#\ 0[36 "2H\ s\ CH2!1#\ 0[33 "2H\ s\ CH2!1#[ EIMS
m:z "rel[ int[#] 297 ðMŁ¦ "05#\ 182 ðM!CH2Ł¦ "099#\ 165
"04#\ 152 "29#\ 150 "60#\ 134 "04#\ 120 "29#[
Extraction and isolation
Dried and powdered aerial parts "09 kg# were
extracted ×1 with 84) EtOH at room temp[ over 1
weeks[ The combined extracts were evapd to dryness
under red[ pres[ "24># and the residue obtained "149 g#
was subjected to CC over silica gel\ eluting with petrol!
EtOAc "09]0# to give an orange oil "79 g#\ and then
eluting with CHCl2 to give a dark gum "54 g#[ Part of
this oil "19 g# was fractionated by silica gel CC eluting
with a petrol!EtOAc gradient[ The frs obtained were
repeatedly chromatographed by silica gel CC using a
petrol!EtOAc mix[ and _nally puri_ed by silica gel CC
using petrol!EtOAc "01]0# to give 0 "423 mg#\ petrol!
EtOAc "04]0# to give 2 "097 mg# and petrol!Me1CO
"19]0# to give 1 "49 mg#[ The CHCl2 part "54 g# was
fractionated by silica gel CC eluting with a CH1Cl1!
EtOAc gradient[ Compounds 3 "09 mg# and 4 "04 mg#
were isolated from frs[ 3 by silica gel CC eluting with
CH1Cl1!EtOAc "5]0#[ Compound 3 was puri_ed by
Sephadex LH!19 CC using CHCl2ÐMeOH "09]0# as
eluant[ Fr[ 4 was subjected to repeated CC over silica
gel eluting with CH1Cl1ÐMe1CO "4]0# to give com!
pound 5 "4 mg#[
Alloevodione "2#
C05H19O4[ Pale yellow oil[ lMeOHmax nm "loge#] 119
"3[23#\ 143 "3[02#\ 210 "2[41#[ IR nfilmmax cm−0] 1869\
1839\ 0691\ 489\ 0347\ 0276\ 0251\ 0181\ 0949[ 0H
NMR "CDCl2#] d 5[40 "0H\ d\ Jꢀ09[9 Hz\ H!3#\ 4[43
"0H\ d\ Jꢀ09[9 Hz\ H!2#\ 2[76 "2H\ s\ −OCH2#\ 2[74
"2H\ s\ −OCH2#\ 2[79 "2H\ s\ −OCH2#\ 1[36 "2H\ s\
CH2CO−6#\ 0[28 "5H\ s\ `em!dimethyl#[ 02C NMR
"CDCl2#] d 199[6 "CꢀO#\ 049[5\ 049[2\ 034[7 "C!8#\
028[7\ 018[1 "C!2#\ 010[0 "C!6#\ 005[3 "C!3#\ 000[2 "C!
09#\ 65[5 "C!1#\ 51[0 "!OCH2#\ 50[3 "−OCH2#\ 50[0
"−OCH2#\ 21[4 "−COCH2#\ 16[7 "CH2!1#[ EIMS m:z
"rel[ int[#] 181 ðMŁ¦ "20#\ 166 ðM!CH2Ł¦ "099#\ 136
"18#[
Compound 2a
C05H11O4[ Pale yellow oil[ IR nfilmmax cm−0] 2447\
1863\ 1829\ 0528\ 0484\ 0355\ 0306\ 0233\ 0170\ 0021\
0923\ 886[ 0H NMR "CD2COCD2#] d 5[42 "0H\ d\
Jꢀ09[9 Hz\ H!3#\ 4[56 "0H\ d\ Jꢀ09[9 Hz\ H!2#\ 4[95
"0H\ q\ Jꢀ5[6 Hz\ H!0?#\ 2[75 "2H\ s\ −OCH2#\ 2[71
"2H\ s\ −OCH2#\ 2[66 "2H\ s\ −OCH2#\ 0[34 "2H\ d\
Jꢀ5[6 Hz\ H!1?#\ 0[30 "5H\ s\ `em!dimethyl#[ 02C
NMR "CD2COCD2#] d 041[4 "C!6#\ 038[4 "C!4#\ 036[3
"C!8#\ 030[1 "C!5#\ 029[2 "C!2#\ 012[3 "C!7#\ 006[7 "C!
3#\ 001[4 "C!09#\ 66[3 "C!1#\ 53[3 "C!0?#\ 51[0
"−OCH2#\ 51[9 "−OCH2#\ 50[3 "−OCH2#\ 17[1 "CH2!
1#\ 16[83 "CH2!1#\ 14[9 "C!1?#[ EIMS m:z "re[ int[#] 183
ðMŁ¦ "06#\ 168 ðM!CH2Ł¦ "099#\ 150 "01#\ 120 "7#[
Leptonol "0#
C04H07O4[ Yellow oil[ lMeOHmax nm "loge#] 197
"3[06#\ 152 "3[36#\ 200 "3[90#\ 243 "2[47#[ IR nfilmmax
cm−0] 1869\ 1829\ 0539\ 0599\ 0267\ 0253\ 0199\ 0944[
0H NMR "CDCl2#] d 02[46 "0H\ s\ OH!4#\ 5[54 "0H\
d\ Jꢀ09[0 Hz\ H!3#\ 4[38 "0H\ d\ Jꢀ09[0 Hz\ H!2#\
2[86 "2H\ s\ −OCH2#\ 2[65 "2H\ s\ −OCH2#\ 1[50 "2H\
s\ −COCH2#\ 0[36 "5H\ s\ `em!dimethyl#[ 02C NMR
"CDCl2#] d 192[4 "CꢀO#\ 045[3\ 044[5\ 042[7\ 023[0\
015[5 "C!2#\ 005[9 "C!3#\ 097[1\ 094[8\ 67[2 "C!1#\ 50[0
"!OCH2#\ 50[0 "−OCH2#\ 21[9 "−COCH2#\ 17[2
"CH2Ð1#[ EIMS m:z "rel[ int[#] 167 ðMŁ¦"10#\ 152 "099#\
122 "6#[
Methylation of 0 to give evodione
Compound 0 "19 mg# in dry Me1CO "0 ml# was
re~uxed with Me1SO3 "49 ml# in the presence of dry
K1CO2 "019 mg# for 3 hr\ then _ltered\ inorganic salts
washed out with hot Me1CO and combined\ _ltered
and conc[ The residue was subjected to CC eluting
with petrol!EtOAc "09]0# to give evodione "2# "04 mg#\
Acetyleptonol "0b#
0
yield 69)[ IR\ MS and H NMR data identical to
C06H19O5[ Pale yellow oil[ 0H NMR "CDCl2#] d 5[12
"0H\ d\ Jꢀ8[8 Hz\ H!3#\ 4[59 "0H\ d\ Jꢀ8[8 Hz\ H!2#\
2[81 "2H\ s\ −OCH2#\ 2[73 "2H\ s\ −OCH2#\ 1[35 "2H\
s\ −COCH2#\ 1[13 "2H\ s\ −OCOCH2#\ 0[35 "5H\ s\
`em!dimethyl#[ EIMS m:z "rel[ int[#] 219 ðMŁ¦ "06#\
167 "42#\ 152 "099#\ 124 "14#[
natural product[
Synthesis of 1 from leptol A
Leptol A "29 mg# was dissolved in MeOH "2 ml#
and HCO1H "9[4 ml# added to the soln[ The mixt[ was

0943
GUO!LIN LI AND DA!YUAN ZHU
REFERENCES
stirred continuously for 4 hr at room temp[\ neu!
tralized with satd NaHCO2 soln\ extracted with Et1O\
the organic layer washed with brine and dried
"Na1SO3#[ Removal of solvent gave a residue which
was subjected to CC using petrol!EtOAc "7]0# to fur!
nish 1 "17 mg#\ yield 78)[
0[ Li\ G[ L[\ Zeng\ J[ F[\ Song\ C[ Q[ and Zhu\ D[ Y[\
Phytochemistry\ 0886\ 33\ 0064[
1[ Ahluwalia\ V[ K[\ Arora\ K[ K[ and Manchanda\
S[\ Indian Journal of Chemistry\ 0871\ 10B\ 0982[
2[ Arnone\ A[ and Cardillo\ G[\ Tetrahedron Letters\
0856\ 32\ 3190[
3[ Kirby\ K[ D[ and Sutherland\ M[ D[\ Australian
Journal of Chemistry\ 0845\ 8\ 300[
4[ Ahluwalia\ V[ K[ and Jain\ A[\ Goyal\ M[\ Indian
Journal of Chemistry\ 0873\ 12B\ 055[
Reduction of alloevodione "2# to `ive compound 2a
Alloevodione "29 mg# was dissolved in 3 ml of
MeOH and NaBH3 "239 mg# added to this soln in ten
batches at room temp[ The mixt[ was stirred con!
tinuously for 4 hr at room temp[ after addition of
NaBH3 was complete[ MeOH was then removed and
the residue dissolved in EtoAc "04 ml# and H1O[ The
EtoAc layer was separated and concd^ the residue
after silica gel CC eluting with petrol!EtOAc "09]0#
gave compound 2a "12 mg#\ yield 65)[
5[ Monache\ G[ D[\ Rosa\ M[ C[ D[\ Scurria\ R[\ et
al[ Phytochemistry\ 0880\ 29\ 0738[
6[ Wang\ Y[\ Hamburger\ M[\ Gueho\ J[\ et al[ Phy!
tochemistry\ 0878\ 17\ 1212[
7[ Delgado\ G[\ Cardenas\ H[\ Pelaez\ G[\ et al[ Jour!
ꢁ
ꢁ
nal of Natural Products\ 0873\ 36\ 0931[