Phenolic compounds from Peperomia obtusifolia

Article abstract of DOI:10.1016/S0031-9422(97)01050-9

From the aerial parts of Pepermia obtusifolia, five phenolic compounds bearing a methyl, an isoprenyl and a geranyl group on a benzene ring core have been isolated. The structures were determined by the spectroscopic analysis including 2D NMR techniques and synthesis.

Full text of DOI:10.1016/S0031-9422(97)01050-9

Phytochemistry\ Vol[ 38\ No[ 0\ pp[ 118Ð121\ 0887
Þ 0887 Elsevier Science Ltd[ All rights reserved
Printed in Great Britain
Pergamon
\
9920Ð8311:87:,Ðsee front matter
PII] S9920Ð8311"86#90949Ð8
PHENOLIC COMPOUNDS FROM PEPEROMIA OBTUSIFOLIA
TOSHIYUKI TANAKA\ FUJIO ASAI and MUNEKAZU IINUMAꢀ
Department of Pharmacognosy\ Gifu Pharmaceutical University\ 5!0 Mitahora!higashi 4 chome\ Gifu 491\ Japan
"Received in revised form 29 October 0886#
Key Word Index*Peperomia obtusifolia^ Piperaceae^ piperogalin^ peperobtusins AÐB^ iso!
peperobtusin A\ 1?!hydroxydihydrochalcone[
Abstract*From the aerial parts of Pepermia obtusifolia\ _ve phenolic compounds bearing a methyl\ an
isoprenyl and a geranyl group on a benzene ring core have been isolated[ The structures were determined by
the spectroscopic analysis including 1D NMR techniques and synthesis[ Þ 0887 Elsevier Science Ltd[
All rights reserved
0
INTRODUCTION
that 0 had a benzene ring[ The H and 02C NMR
spectrum showed the presence of a geranyl\ an isop!
renyl\ a methyl and two phenolic hydroxyl groups[ By
NMR spectral analysis "HH long range COSY\ CH
COSY\ COLOC and NOE experiments#\ 0 was ident!
i_ed as piperogalin which has been isolated from P[
`alioides ð2Ł[
Some Peperomia species have been used as folk medi!
cine\ e[g[ P[ japonica Makino has been used for the
treatment of malignant tumors ð0Ł[ Compared with the
genus Piper\ few phytochemical studies of Peperomia
have been reported ð1Ð5Ł[ Nevertheless\ some struc!
turally attractive compounds have been isolated\ for
example\ unique secolignans "peperomins AÐD# from
P[ japonica Makino ð1Ł and P[ `labella "Sw[# A[ Dieter
ð2Ł and prenylated phenols with the antiparasite
activity from P[ `alioides H[B[K ð3\ 4Ł[ In this paper
we describe the isolation and structural determination
of phenolic compounds in aerial parts of P[ obtusifolia[
A[ Dieter which grows from Mexico to the northern
parts of South America and is well known as a popular
foliage plant[
Compound 1\ a pale yellow oil\ gave M¦ at m:z
215[1146 in the HR!EIMS which corresponds to
C11H29O1[ Compound 1 gave a monomethyl ether "1a#
by the usual methylation[ The UV spectral data sug!
gested that 1 was a benzene derivative[ The 0H NMR
spectrum showed the presence of a methyl "d 1[19#\ an
isoprenyl ðd 0[55\ 0[66 "2H each\ br s\ Me#\ 2[13\ 2[25
"0H each\ dd\ J ꢁ 04\ 6 Hz\ CH1#\ 4[04 "0H\ t like m\
CH1#Ł\ a phenolic hydroxyl "d 3[64# and an aromatic
0
proton in a singlet "d 5[04#[ The H NMR spectrum
also exhibited the presence of mutually coupled two
methylenes ðd 0[69 "0H\ m#\ 0[77 "0H\ ddd\ J ꢁ 03\ 4\
4 Hz# and 1[31 "0H\ ddd\ J ꢁ 06\ 4\ 4 Hz#\ 1[50 "0H\
ddd\ J ꢁ 06\ 4\ 4 Hz#Ł\ three further ole_nic protons
ð4[34 "d\ J ꢁ 05 Hz#\ 4[65 "br d\ J ꢁ 00 Hz# and 5[22
"dd\ J ꢁ 05\ 00 Hz#Ł\ two vinyl methyls ð0[55\ 0[62 "2H
each\ br s#Ł and a tertiary methyl group ð0[30 "2H\
s#Ł[ HH correlations in the HH long range COSY
spectrum were observed as in Fig[ 0 and NOEs as in
Fig[ 1[ Thus\ 1 had a C09 alkyl chain composed of an
E!diene unit drawn as a bold line in Fig[ 0[ The NOE
experiments indicated that ortho!positions of the aro!
matic proton were substituted with the phenolic OH
"OCH2 in the case of 1a# and the methyl group[ The
isoprenyl group was attached at the ortho!position
to the methyl group[ Therefore\ the structure of this
compound is either 1 or 1?[ In the 02C NMR spectrum\
quaternary carbons bearing an oxygen were observed
at d 041[46 and 042[32\ indicating that 1 had a resorci!
nol\ not a catechol oxygenation[ The isoprenyl meth!
RESULTS AND DISCUSSION
Fresh aerial parts of P[ obtusifolia were homo!
genized in MeOH and left at room temperature[ After
_ltration\ the residues were further extracted with
MeOH[ The _rst MeOH solution and the second solu!
tion were combined and concentrated in vacuo to give
a dark greenish extract[ The EtOAc soluble portion
of the extract after partition was chromatographed on
silica gel eluted with a n!hexane!Me1CO mixture to
give _ve compounds "0Ð4# after further puri_cation
with silica gel or Sephadex LH19 column chro!
matography\ and preparative TLC[
Compound 0\ a yellow oil\ gave M¦ at m:z 217[1284
in the high resolution EIMS "HR!EIMS# which cor!
responds to C11H21O1[ The UV spectrum indicated
ꢀ Author to whom correspondence should be addressed[
118

129
T[ TANAKA et al[
ylene carbon at d 14[54 suggested that both ortho! trum "Fig[ 2#[ The quaternary carbon "d 042[32# was
positions of the isoprenyl group were substituted with correlated with the isoprenyl methylene protons
a C! or O!substitution ð5Ł[ These results showed that through 2J[
the structure was 1\ and named peperobtusin A\ which
Compound 2\ a pale yellow oil\ gave M¦ at m:z
was substantiated by the analysis of the COLOC spec! 215[1153 in the HR!EIMS[ All spectral data of 2 were
very similar to those of 1[ However 1 reacted with
Gibbs reagent to become purple\ 2 did not[ Hence\
a para!position of the hydroxyl group in 2 was not
substituted[ The structure of 2 is an isomer of 1\ in
which the C09 alkyl chain was cyclized with the other
hydroxyl group at C!0[ The structure of 2\ named
isopeperobtusin A\ was con_rmed by the results of
COLOC spectrum and NOE experiments[
Compound 3\ a yellow oil\ gave M¦ at m:z 239[1944
in the HR!EIMS\ which indicated the empirical for!
0
mula C11H17O2[ In the H NMR spectrum\ the pres!
ence of an isoprenyl\ a methyl and a C09 alkyl chain
was exhibited as in 1 and 2[ However the aromatic
Fig[ 0[ HH correlations in HH long range COSY "PI0 ꢁ 099
proton and phenolic hydroxyl group observed in 1
ms# of 1[
and 2 were lost in 3[ The 02C NMR spectrum showed
Fig[ 2[ CH long range correlations in COLOC spectrum
Fig[ 1[ NOE interactions in DIFNOE of 1 and 1a[
"J ꢁ 09 Hz# of 1[

Phenolic compounds from Peperomia obtusifolia
120
the presence of two carbonyl groups at d 071[59 and MHz\ CDCl2#] d 0[48 "2H\ br s\ Me\ H!19#\ 0[56 "2H\
075[33\ which suggested that 3 was a para! or ortho! br s\ Me\ H!10#\ 0[61 "2H\ br d\ J ꢁ 0 Hz\ Me\ H!04#\
benzoquinone derivative of 1 or 2[ NOEs were 0[68 "5H\ br s\ Me×1\ H!09 and 05#\ 1[94 "1H\ t like
observed between the methyl group and the methylene m\ CH1\ H!00#\ 1[97 "1H\ t like m\ CH1\ H!01#\ 1[19
protons of isoprenyl group\ and between the methyl "2H\ br s\ Me\ H!11#\ 2[16 "1H\ br d\ J ꢁ 6 Hz\ CH1\
group on a pyran ring "d 0[38# and the same methylene H!06#\ 2[28 "1H\ br d\ J ꢁ 6 Hz\ CH1\ H!6#\ 4[92 "0H\
protons[ These results indicated that the substitution br s\ C!0!OH#\ 4[94 "0H\ t like m\ CH1\ H!02#\ 4[02
pattern of the methyl\ the isoprenyl and the C09 alkyl "0H\ t like m\ CH1\ H!07#\ 4[14 "0H\ t like m\ CH1\
chain unit was the same as 1[ Therefore\ the structure H!7#\ 4[24 "0H\ br s\ C!2!OH#\ 5[14 "0H\ s\ H!5#[
of 3 was the ortho!benzoquinone derivative of 1\ which
Compound 1 "peperobtusin A#[ A pale yellow oil[ ðaŁD
was con_rmed by the analysis of the COLOC spec! ¦1[5> "c ꢁ 9[28\ MeOH#\ HREIMS M¦ m:z 215[1146
trum\ and named peperobtusin B[
"Calcd[ 215[1243 for C11H29O1#\ EIMS m:z "rel[ int[#]
Compound 4\ colorless oil\ gave M¦ at m:z 215 "099\ M¦#\ 200 "01#\ 172 "19#\ 169 "10#\ 14 "06#\
115[0997 in the HR!EIMS corresponds to C04H03O1[ 132 "13#\ 116 "59#\ 194 "34#\ 078 "31#\ 050 "29#\ 038
In the 0H NMR spectrum\ characteristic signals based "64#\ 011 "02#\ 096 "34#\ 80 "06#[ UV lmMaexOH] 128sh\
0
on dihydrochalcone were observed as well as a mono! 166sh\ 172 nm\ H NMR "399 MHz\ CDCl2#] d 0[30
substituted and a 0\1!disubstituted benzene ring\ sug! "2H\ s\ Me\ H!09#\ 0[55 "5H\ br s\ Me×1\ H!05 and
gesting the structure of 4 was 1?!hydroxydihydro! 19#\ 0[69 "0H\ m\ H!7#\ 0[62 "2H\ br s\ Me\ H!04#\ 0[66
chalcone[ A hydrogenated product of 1?!hydroxy! "2H\ br s\ Me\ H!10#\ 0[77 "0H\ ddd\ J ꢁ 03\ 3\ 3 Hz\
chalcone prepared by condensation of benzaldehyde CH1\ H!7#\ 1[19 "2H\ br s\ Me\ H!11#\ 1[31\ 1[50 "0H
and 1!hydroxyacetophenone was identi_ed with 4[ each\ ddd\ J ꢁ 06\ 4\ 4 Hz\ H!6#\ 2[13\ 2[25 "0H each\
Dihydrochalcones have been isolated from some Pip! dd\ J ꢁ 04\ 6 Hz\ CH1\ H!06#\ 3[64 "0H\ br s\ C!0Ð
eraceaeous plants such as Piper aduncum L[ ð6Ł\ but OH#\ 4[04 "0H\ t like m\ CH1\ H!06#\ 4[43 "0H\ d\
4 has a very simple and unusual substitution for a J ꢁ 05 Hz\ CH1\ H!00#\ 4[64 "0H\ br d\ J ꢁ 00 Hz\
naturally occurring dihydrochalcone[
CH1\ H!02#\ 5[04 "0H\ br s\ H!5#\ 5[22 "0H\ dd\
J ꢁ 05\ 00 Hz\ CH1\ H!02#[
Methylation of 1[ Peperobtusin A "1\ 4 mg# was
treated with CH2I:K1CO2 in dry acetone under re~ux[
After _ltration\ the reaction mixture was condensed
in vacuo and puri_ed by preparative TLC "solvent]
EXPERIMENTAL
Plant material
Plant material of Peperomia obtusifolia A[ Dieter benzene# to give 1a "2 mg#[ EIMS m:z "rel[ int[#] 239
horticulturally cultivated at Nagoya City\ Japan were "099\ M¦#[ 0H NMR "399 MHz\ CDCl2#] d 0[39 "2H\
purchased in March\ 0886[ The voucher specimens are s\ Me\ H!09#\ 0[55 "5H\ br s\ Me×1\ H!05 and 19#\
deposited at the Herbarium of Gifu Pharmaceutical 0[69 "0H\ m\ H!7#\ 0[62 "2H\ br s\ Me\ H!04\ 0[67 "2H\
University[
br s\ Me\ H!10#\ 0[89 "0H\ ddd\ J ꢁ 03\ 4\ 4 Hz\ H!7#\
1[16 "2H\ br s\ Me\ H!11#\ 1[38\ 1[51 "0H each\ ddd\
J ꢁ 05\ 4\ 4 Hz\ CH1\ H!6#\ 2[17\ 2[26 "0H each\ dd\
J ꢁ 03\ 5 Hz\ CH1\ H!06#\ 2[65 "2H\ s\ OCH2#\ 4[03
Extraction and isolation
Fresh aerial parts "7 kg# of P[ obtusifolia homo! "0H\ t like m\ CH1\ H!07#\ 4[45 "0H\ d\ J ꢁ 05 Hz\
genized with a mixer were added to MeOH "04 l#[ CH1\ H!00#\ 4[65 "0H\ br d\ J ꢁ 00 Hz\ CH1\ H!
After _ltration\ the residues were again left in MeOH 02#\ 5[11 "0H\ br s\ H!5#\ 5[27 "0H\ dd\ J ꢁ 05\ 00 Hz\
"04 l# at room temp[ Both MeOHs were combined and CH1\ H!01#[
concentrated in vacuo to give a greenish extract "116
Compound 2 "isopeperobtusin A#[ A pale yellow oil[
g#[ The extract was partitioned with EtOAc to give an ðaŁD 9>[ HREIMS M¦ m:z 215[1153 "Calcd[ 215[1243
EtOAc soluble extract "091 g#[ The EtOAc extract was for C11H29O1#\ EIMS m:z "rel[ int[#] 215 "099\ M¦#\
chromatographed on silica gel eluted with n!hexaneÐ 200 "01#\ 172 "05#\ 169 "07#\ 144 "06#\ 132 "14#\ 116
Me1CO mixture[ The n!hexaneÐMe1CO "7]0# fraction "44#\ 194 "42#\ 078 "21#\ 050 "19#\ 038 "84#\ 011 "19#\
was chromatographed on Sephadex LH19 "solvent\ 096 "64#\ 80 "27#\ UV lmMaexOH] 126\ 165sh\ 179 nm\ H
0
Me1CO#[ Crude phenolic compounds were further NMR "399 MHz\ CDCl2#] d 0[30 "2H\ s\ Me\ H!09#\
chromatographed on silica gel column\ and puri_ed 0[58 "2H\ br s\ Me\ H!05#\ 0[63 "5H\ br s\ Me×1\ H!
by preparative TLC ðsolvent systems] CHCl2^ benzene^ 04 and 19#\ 0[79 "0H\ m\ H!7#\ 0[70 "2H\ br s\ Me\ H!
cyclohexaneÐMe1CO "19]0#^ cyclohexaneÐbenzene 10#\ 1[11 "2H\ br s\ H!11#\ 1[44\ 1[50 "0H each\ ddd\
"4]0# and benzeneÐMe1CO "4]0#Ł repeatedly to give 0 J ꢁ 05\ 7\ 5 Hz\ CH1\ H!6#\ 2[17 "1H\ br d\ J ꢁ 6 Hz\
"019 mg#\ 1 "45 mg#\ 2 "37 mg#\ 3 "5 mg# and 4 "01 CH1\ H!06#\ 4[04 "0H\ br s\ C!2ÐOH#\ 4[05 "0H\ t like
mg#\ respectively[
m\ CH1\ H!07#\ 4[48 "0H\ d\ J ꢁ 04 Hz\ CH1\ H!
Compound 0 "pipero`alin#[ A yellow oil[ HREIMS 00#\ 4[65 "0H\ br d\ J ꢁ 00 Hz\ CH1\ H!02#\ 5[23 "0H\
M¦ m:z 217[1284 "Calcd[ 217[1491 for C11H21O1#\ br s\ H!5#\ 5[39 "0H\ dd\ J ꢁ 04\ 00 Hz\ CH1\ H!01#[
EIMS m:z "rel[ int[#] 217 "29\ M¦#\ 202 "2#\ 132 "19#\
Compound 3 "peperobtusin B#[ A yellow oil[ ðaŁD
194 "30#\ 192 "34#\ 078 "12#\ 066 "06#\ 051 "06#\ 051 ¦2[2> "c ꢁ 9[95\ MeOH#\ HREIMS M¦ m:z 239[1944
"07#\ 038 "099#\ UV lmMaexOH] 126\ 171 nm\ 0H NMR "399 "Calcd[ 239[1927 for C11H17O2#\ EIMS m:z "rel[ int[#]

121
T[ TANAKA et al[
115[9883 for C04H03O1#\ EIMS m:z "rel[ int[#] 115 "34\
Table 0[ 02C NMR Spectral data of 0Ð3
MeOH
M¦#\ 197 "19#\ 196 "1#\ 010 "099#\ 80 "05#[ UV l
]
max
104\ 141\ 213 nm\ 0H NMR "399 MHz\ CDCl2#] d 2[95
"1H\ t\ J ꢁ 7 Hz\ CH1\ H!6#\ 2[36 "1H\ t\ J ꢁ 7 Hz\
CH1\ H!7#\ 5[79 "0H\ ddd\ J ꢁ 8\ 7\ 1 Hz\ H!4?#\ 5[82
"0H\ dd\ J ꢁ 7\ 1 Hz\ H!2?#\ 6[07 "0H\ m\ H!3#\ 6[19
"1H\ d like m\ H!1 and 5#\ 6[16 "1H\ t like m\ H!2 and
4#\ 6[26 "0H\ ddd\ J ꢁ 7\ 7\ 1 Hz\ H!3?#\ 6[43 "0H\ dd\
J ꢁ 8\ 1 Hz\ H!5?#\ 02C NMR "099 MHz\ CDCl2#]
d 039[46 "C!0#\ 017[32 "C!1 and 5#\ 017[13 "C!2 and 4#\
015[03 "C!3#\ 18[65 "C!6#\ 28[78 "C!7#\ 194[03 "C!8#\
051[17 "C!1?#\ 007[61 "C!2?#\ 025[02 "C!3?#\ 007[22 "C!
4?#\ 018[54 "C!5?#[
Synthesis of 1?!hydroxydihydrochalcone "4#[ 1?!Hyd!
roxychalcone "09 mg# which was prepared by the alk!
ali "KOH!79) MeOH# condensation of 1?!hydroxy!
acetonephenone and benzaldehyde was hydrogenated
with H1!Pd:C in EtOAc[ The resulting compound was
identical with 4 "TLC\ NMR and EIMS#[
Carbon No[
0
1
2
3
0
1
2
3
4
5
6
7
8
09
00
01
02
03
04
05
06
07
08
19
10
11
041[46
000[27
042[32
007[02
024[10
098[61
11[43
041[05
095[90
040[03
019[90
023[85
096[67
06[92
041[46ꢀ
095[66
041[37ꢀ
004[75
024[17
009[54
06[98
075[33
006[53
041[02
027[94
032[15
071[59
05[25
20[90
68[25
15[74
020[85
015[98
013[95
022[44
15[99
010[84
026[33
05[03
20[41
64[87
16[24
20[85
64[61
15[71
28[56
15[27
012[71
022[21
14[69
023[06
014[99
013[48
024[09
14[67
023[04
014[28
013[49
024[21
14[65$
07[20
06[71
07[10
07[30
14[61
14[43
13[25
14[46
011[37
020[81
14[54
012[16
029[16
14[75
011[49
023[93
14[65$
06[73
008[43
025[79
14[61
06[86
00[58
Acknowled`ements*This study was supported in part
by a Grant!in Aid for Scienti_c Research "No[
98930083# from the Ministry of Education\ Science\
and Culture\ Japan[
06[55
06[84
08[63
08[36
08[88
Measured in CDCl2 "099 MHz#[ ꢀ interchangeable\ $ over!
lapping[
REFERENCES
All carbons were assigned by the aid of CH COSY and
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Hz\ CH1\ H!02#\ 5[24 "0H\ dd\ J ꢁ 04\ 09 Hz\ CH1\
1268[
H!01#[
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6[ Orjala\ J[\ Wright\ A[ D[\ Behrends\ H[\ Folkers\
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4
"1?!hydroxydihydrochalcone#[
A
colourless oil[ HREIMS M¦ m:z 115[0997 "Calcd[