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Phytochemistry,
FURTHER
5-METHYLCOUMARIN
DERIVATIVES
FROM MUTZSIA
ORBIGNYANA
C. ZDERO,
F. BOHLMANN
and J.
SOLOMON*
Institute of Organic Chemistry, Technical University of Berlin, D-1000 Berlin 12, F.R.G.; *Herbario Nacionale de Bolivia, La Paz,
Bolivia
(Revised received 18 August 1987)
orbignyana;
Abstract-The
aerial parts of Mutisia orbignyana afforded in addition to known compounds 24 new derivatives of
4-hydroxy-5-methylcoumarin.
The structures were elucidated by high field NMR techniques and a few chemical
transformations. The chemotaxonomic relevance of these compounds is discussed briefly.
INTRODUCTION
R
R
R
4*
Me
CH,OH
H
H
CH,OH
H
H
22
Me
OH
H
H
H
9*
R
R
X
CH,OH
H
aO0H.H
5*
CHIOH
OH
H
10*
11
12*
Me
Me
CHrOH
OH
H
OH
BO0H.H aO0H.H =O
891
CHO
H
H
CHO
H
H
22
l3
14
CHO
H
I
2-2
CH,OH
H
0H.H
8
CH,OH
H
OH
C. ZDEROet al.
892
OOH
15
16
OH
R?
OH
18
17
19
19a
20
20a
20b
n= IFI
k = ,k
x=0
X = COAc),
X = ((IMe):
OAC
OAc
21
2a-&I, !h, lOa, 12a. 15a and 16a are the corresponding
5a, 8a, IOak, lla and 14a the diacetates
acetates,
893
C. ZDERO et al.
894
Table
1. H NMR spectral
a-values)
2a
3a
4a
5a
8a
Multiplicity
3
6
7
8
9
I
2
5.66
7.17
7.37
7.03
2.67
4.67
5.52
5.68
7.17
7.37
7.03
2.67
4.80
5.65
5.66
7.16
7.36
7.02
2.65
4.78
5.72
5.65
7.17
7.37
7.03
2.67
4.72
5.83
5.64
7.18
7.38
7.04
2.67
4.70
5.83
5.65
7.18
7.37
7.03
2.67
4.71
5.81
5.61
7.15
7.36
7.02
2.64
4.67
5.76
5.66
7.18
7.39
7.04
2.66
4.84
6.02
5.67
7.20
7.41
7.05
2.70
5.17
6.43
5.65
7.20
7.41
7.07
2.70
4.97
6.67
s
hr d
f
hr d
s
2.24
2.22
2.21*
2.22
4.11*
5.16*
5.28*
2.46
2.42*
2.37*
5.65
7.18
7.38
7.03
2.66
4.76
5.77
2.48t
2.40:
2.19
2.16
2.15*
2.16
2.32*
2.20t
2.14t
5.66t
5.10
1.69
1.60
5.10
1.58
1.72
9.95 5
9.52 s
4.67
hr s
2.08
1.99
s
5
4
2.14
5
6
8
9
5.10
1.69
1.63
5.12
1.69
1.63
5.08
1.69
I .62
5.10
5.09
1.68
1.69
5.10
1.74
5.11
1.68
1.60
I .62
1.69
1.62
10
1.77
4.26
4.66
4.18
4.61
1.79
OAc
*t;
2.08
tdt;
:dd;
1.77
2.13
2.16
3,4,4a,
Table
9a
10a
lOaAc*
5.64
7.19
7.39
7.04
2.67
4.74
5.79
5.329
5.61
7.17
7.37
7.02
2.65
4.66
5.81
5.22
1.90
1.95
9;
9;
10
OAc
5.68
7.19
7.39
7.04
2.67
4.82
5.74
2.27
1.90
1.70
4.34 t
1.77
5.06
5.03
4.68
2.10
OOH
8.07
8.32
5
6
8
*CDCl,/C,D,:
tn
hr
5.119
1.68
hr s
hr s
4.334
1.78
5.04
1.80
2.10
5.22
1.74
4.98
4.9 1
1.77
2.06
2.05
reaction of 4-hydroxy-Smethyl
coumarin with hydroxyhydroquinone.
We have named 21, mutisifurocoumarin
diacetate.
The chemistry of this Mutisia
species again shows that
Smethyl coumarins are characteristic
for parts of the
subtribe Mutisiinae [4]. However, these compounds are
not present in all genera and also not in all Mutisia
species. A reinvestigation
of M. acuminata
R. et P. again
3
6
7
8
9
1
2
4
hr t
#d.
2.39
5.04
1.71
1.64
4.74g
r 4.706
2.09.
2.08
hr d
J-values)
12a
13
14a
5.62
7.18
7.37
7.03
2.66
4.68
5.79
5.19
2.1311
1.9311
5.19 t
1.75
4.97
4.95
1.78
2.08(6H)
5.66
7.18
7.38
7.04
2.65
4.79
5.75
2.53
5.71
7.18
7.41
7.07
2.72
5.28
6.71
2.65
5.66
7.18
7.38
7.03
2.66
4.77
5.74
2.17
5.48
6.98
6.89
6.63
2.48
4.10
5.42
2.69 d
5.62
7.17
7.37
7.05
2.66
4.73
5.84
5.67 d
2.98 t
1.80
5.5511
5.885
5.17 t
1.73
4.96
4.92 I
4.65
2.07(6H)
5.65 d
1.35 s
5.64 d
1.37 s
1.87
5.95
5.78
9.47
_
1.35 5
1.36s
4.46
1.73 s
1.78
2.13
7.82
7.75
2.90 t
1.90
5.99
5.82
4.69
2.10
lWC,D,)S
16a
Multiplicity
llat
s
hr d
I
hr d
s
hr d
hr t
Nt
br s
br s
hr s
s
IN.
4,5; = 5;,6=5;compound
Further
Table
H
3
6
7
8
9
1
17
3. H NMR spectral
18
5.62
7.18
7.38
7.03
2.67
br d
t
br d
s
d
d(t)
dd
7.20
7.39
7.03
2.65
5.21
5.15
6.22
2.05 m
2.19 m
6
8
9
5.14
1.66
1.53
4.33
4.13
19a
s
br d
t
br d
s
5.65
7.18
7.38
7.04
2.66
derivatives
orbignyana
s
br d
t
br d
s
from Mutisia
5.67
7.20
7.41
7.06
2.68
2Oa
s
br d
t
br d
s
5.65
7.18
7.38
7.04
2.66
895
d-values)
2Ob
s
br d
t
br d
s
5.66
7.18
7.38
7.04
2.66
21
s
br d
t
br d
s
7.38
7.50
7.22
1.92
br d
t
br d
s (H-l 1)
4.56 br d
4.72 br d
4.88 br d
4.82 br d
4.80 br d
5.71 ttt
2.73 br dd
2.37 br dd
4.88 br t
6.26 br t
5.89 br t
5.84 br t
4.45 br t
7.19 d
6.09 d
6.46 d
6.29 dd
5.78 dd
5.74 dd
9.65 d
7.23 d
4.91 d
7.64 s
4.62 dt
br t
br s
br s
d
d
5-methylcoumarin
5.33
1.75
1.72
4.54
4.33
dqq
d
d
br d
br d
2.64
1.79
5.05
1.29
1.28
ddd
ddd
dd
s
s
1.77 br s
1.97 br s
1.90 br s
1.89 br s
2.12 s (6H)
OAc
3.36 s(6H)
OMe
2.38 s(6H)
OAc
*H-3 7.97 s.
J[Hz]:
6,7=7,8=8;
compound
17: 1,2= 10.5; lt,2= 17.5; 5,6=7; 10,,10;=9.5;
compound
18: 1,2=7;
2,4
=2,10-1.5;4,,4;
=15;4;,5=5.5;4;,5=5,6=8.5;6,8=6,9=1.5;10;,10;=13;compound19a:
1,2=7;4,5=7.5;
5;,5;
= 14; 5;,6 =4; 5;,6 =6.5 compounds 20,20a and 20b: 1,2 = 6.5; 4,5 = 16.5; 5,6 = 7.5 (compound 2Oa: 5,6 = 6.5; compound
20b: 5,6 = 5).
representatives.
EXPERIMENTAL
by HPLC (MeOH-H,O,
4: 1) 3mg 16a (R, 1Smin) and 3mg 9a
(R, 1.7 min). HPLC of fraction 4/5 (MeOH-H,O,
4: 1) gave 5 mg
7 (R, 6.8 min) and 100 mg 4a (R, 11.2 min). HPLC of fraction 4/6
(MeOH-H,O,
4: 1) afforded 3 mg 2Oa (R, 5.7 min), 8 mg lla (R,
6.9 min), 8 mg 10a acetate (R, 7.8 min), 20 mg 5a (R, 10.9 min) and
two mixtures (4/6/5 and 4/6/6). TLC of 4/6/5 (E&O-petrol,
3: 1,
three developments)
gave 2 mg 8a (R, 0.65) and 7 mg 14a (R,
0.58). TLC of 4/6/6 (CHCI,-C,H,-Et,O,
2:2: 1, three developments)afTorded 3 mg 18(RJ0.63)and20
mg 14a(R,O.55). HPLC
of fraction 4/7 (MeOH-H,O,
4: 1) gave 30 mg arbutin pentaacetate(R, 1.3 min); H NMR (CDCI,, 400 MHz): 7.OO(br s, H-2,
3,5,6), 5.04 (d, H-l), 5.29(t, H-2), 5.26(t, H-3), 5.17(t, H-4), 3.84
(dd, H-S), 4.30 and 4.18 (dd, H-5), 2.29, 2.08, 2.07, 2.05, 2.04 (s,
OAc) (I [Hz]: 1,2= 7.5; 2,3 = 3,4 =4,5-9;
5,6; = 5; 5,6; = 2.5;
6;,6; = 12.5); 1 mg 13 (R, 5.3 min), 2 mg 12a (R, 6.0 min), 7 mg 19a
(R, 7.0 min) and 20 mg 14a (R, 10.3 min). Fraction 4/8 afforded
1.5 g isorhamnetin
tetra-acetate
and 200 mg rhamnazin
triacetate (only 5% separated by HPLC) and fraction 4/9 2 g quercetin
pentaacetate.
TLC of fraction 4/10 (CHCI,-Et,O,
1: 1) gave 3 mg
21 (R, 0.8).
4-Geranyloxy-5-methyl coumarin (1). Colourless crystals, mp
91, IR vz:$ cm-: 1720, 1610, 1600 (coumarin); MS m/z (rel.
int.): 312.173 [M] (1.5) (talc. for C2,,H2403: 312.173), 297 [M
-Me]+(l.5),
177[M-C,,H,,]+(54),
135(C,H,0,]+(20),
134
[C,H,O,]+
(17), 69 [C,H,]
(100). Identical with synthetic
material.
4-[lo-Hydroxygerany[oxy]-5-methyl
coumarin (2). Colourless
crystals, mp 114; IR v$~~3 cm-: 3360 (OH), 1700, 1610, 1600
(coumarin);
MS m/z (rel. int.): 328.167 [M]
(3) (talc. for
C 20H 240 4 328.167), 310 [M-H,O]+
(5), 201 (7), 177 [M
-C,,H,,O]+
(44), 176 [M-C1,,H,,O]+
(53). 135 [CsH,OJ+
(64), 134 [C,H,OJ+
(82), 69 [C,H,]+
(100). Acetylation
gave
the acetate 2a identical with the natural product; colourless
crystals, mp 57; IR v$:$ cm-: 1740, 1230 (OAc), 1720, 1610,
1600 (coumarin); MS m/z (rel. int.): 370.178 [M] (1.5) (talc. for
896
C. ZDERO et al.
(loo).
4-[lO-Hydroxyneryloxy]-5-methyl coumarin (3). Colourless
crystals, m p 103:'; IR Vma
c(I,x cm
3600 (OH}, 1725, 1610, 1600
(coumarin); MS m/z (rel. int.): 328.167 [ M ] + (3) (calc. for
C20H2,,O,,), 310 (3.51, 201 (12), 177 (57), 135172), 134 (35), 69 (1001.
Acetylation gave the acetate 3a, identical with the natural
product; colourless crystals, nap 109"; IR ~,nax
.,ccl~ cm 1.. 1740, 1230
(OAc), 1725, 1610, 1600 (coumarinl; MS m/z (tel. int.): 370.178
[ M ] + (2) (calc. for C22Hs~Os: 370.1781, 310 18), 295 (4t, 241 (221,
201 (22), 177 (46), 135 (431, 134 (461, 69 (100).
4-[4-Hydroxygeranyloxy]-5-methyl coumarin (4). Colourless
oil; IR Vma
ccl~x cm ~..3580 (OH), 1720, t610, 1595 (coumarin): MS
m/z (tel. int.): 328.167 [ M ] ~ (0.7) (calc. for C2oH2,,O,,: 328.1671,
310(3.5), 201 (I01, 190150), 164143), 135 (100), 134126); [c~]~4 - 2 1
(CHC13; e0.78). Acetylation gave the acetate 4a, colourless
crystals, m p 38'; l R v mcol
a x ' C m ~.. 1740, 12351OAc), 1720, 1610,
1600 (coumarin); MS m/z (rel. int.): 370.178 [ M ] * (11 (calc. for
C22H260~: 370.178), 310 (2), 241 14.5!, 201 (37), 177 (40), 135 (28),
134 121), 69 (100); [c~]:o4 - 1 3 (CHCI3; c3.7).
4-[4,10-Dihydroxygeranyloxy]-5-methyl coumarin (5). Isolated
~ $ CC[e.
as its diacetate 5a, colourless crystals, nap 6 4 : ~t~
'max cm 1 :
1745, 1230 (OAc), 1725, 1610, 1600 (coumarin); M S m/z (rel. int.):
428.184 [ M ] + (5)(calc. for Cs,,H :807: 428.184), 386 (2.5), 369 [ M
--OAc] + (2.2), 368 [ M - H O A c ] " (1), 308 [ 3 6 8 - H O A c ] + (27),
201 (62), 177 (100), 135 (35), 134 (35), 69 (711; [ x ] ~ 4 - 7 (CHCI3:
c0.71.
4-[10-Oxo-qeranyloxy]-5-methyl coumarin (6). Colourless crystals, m p 67; IR Vma
CCl,
x cm ~: 2740, 1730(CHO), t720, 1612, 1600
(coumarin); MS m/z (rel. int.): 326.152 [ M ] 11.5} (calc. for
C20H220,,: 326.152), 257 [ M - C s H g ~ ] + (221, 177 (48), 135 (32),
134 (181, 69 (100).
4-[lO-Oxo-neryloxy]-5-methyl coumarin (7). Colourless crystals, m p 144~; IR vC~ '~ cm ~ 2740, 1710(CHOI, 1700, 1610, 1600
(coumarin); MS m/z (rel. int.): 326.152 [ M ] ~ (2.5) (calc. for
C20H220,,: 326.1521, 257 [ M - C s H 9 ] + (20), 201 (24), 177 (56),
135 (60), 134 (44), 69 (1001. Boranate reduction ( M e O H , 2 0 , 5
min) gave after T L C (CHC13 C6H~, Et:(), l : l : l ) 3, identical
with the natural product.
4-[5,10-Dihydroxy.qeranyloxy]-5-methyl eoumarin (8). Isolated
as its diacetate 8a, colourless oil; IR Vma
CCl.,
x cm 1.. 1745, 1250
(OAc), 1730, 1620, 1610 (coumarin): MS m/z (rel. int.): 428.184
[ M ] ~ (0.2) (calc. for C24H2807: 428.1841, 386 (1), 368 [M
- HOAc) + (1.51, 308 (34), 201 (46), 1771421. 1351361, 134(351, 133
(81), 85 [ C 5 H 9 0 ] (1001.
4-[ 10-Hydroxy-6-hydroxperoxy-7,9-dehydro-6,7-dihydro,qeranyloxy]-5-methvl coumarin (9). Colourless oil: IR VCm~ldcm ~:
3300 (OH), t735, 1225 (OAc), 1720, 1610 (coumarin); MS m/z (rel.
int.): 402.168 [ M ] ~ tl) (calc. for C22H2~07: 41/2.1681, 384 [M
- H s O ]+ (2), 368 [ M - H 2 0 2 ] ~ (11, 324 [ 3 8 4 - H O A c ] * (3), 24t
(23), 1771521, 135(611, 134163), 69111X)); [:~J~4
15 (CHC13; c0.1 ).
4-[4-ftydroxy-6-hydroperoxy-7,9-dehydro-6,7-dihydrogeranyloxy]-5-methyl coumarin (10). Isolated as its acetate 10a, colourless oil; IR Vmax~Cm
col
. ~.. 1735, 1230(OAc), 1725, t610(coumarinl;
MS m/z (rel. int.): 402.168 [MJ ~ t0.8)(calc, for C22H2607:
402.168), 384 (2), 324 (4), 201 (281, 177 (38k 135 142), 134 (40), 69
(100). Aeetylation gave the diacetate 10a acetate, colourless oil;
CCb.
IRvm~ix
cm 1.. 1740, 1235 (OAc), 1725, 1615, 1601/(coumarinl;
MS m/z (rel. int.): 444.178 [ M ] ~ (0.5) (talc. for C2,,H280,:
444.178), 369 [M - O O A c ] * (1.2), 368 [M - H O O A c ] " (0.71, 308
[368-- H O A c ] 1131,201140), 177126i, 151166), 135130), 1341381,
133 (641, 55 (1001:[7124
6 4 / C H C I 3 : c0.291.
4-[4-ttydroxy-6-epi-hydroperoxy-7,9-dehydro-6,7-dihydro,qeranyloxy]-5-methyl eoumarin (111. Isolated as its diacetate l l a .
Further
S-methylcoumarin
derivatives
s, 135.3s, 126.9d, 131.6d, 115.6d, 154.5s, 111.8s,21.3q;C-l-C6: 166.2 s, 140.3 s, 115.4 d, 141.2 s, 152.3 s, 107.4 d; OAc: 20.5,20.7
4, 170.5 s (2x).
Acknowledgement-We
einschaft for financial
thank
support.
the Deutsche
REFERENCES
1. Cabrera,
13, 1.
Forschungsgem-
897