Prenylated benzoic acids from Rapanea myricoides

Article abstract of DOI:10.1021/np980098j

Investigation of leaves from the shrub Rapanea myricoides led to the isolation of two diprenylated benzoic acids. One was the known compound 5- carboxy-7-(3'',3''-dimethylallyl)-2-(1'-hydroxy-1',5'-dimethylhex-4'-enyl)- 2,3-dihydrobenzofuran (1), while the other was assigned as the new diol 2 (3- (2',3'-dihydroxy-3',7'-dimethyloct-6'-enyl)-4-hydroxy-5-(3'',3''- dimethylallyl)benzoic acid, myricoidiol). These compounds were initially characterized through analysis of their spectroscopic data and comparison with some simpler synthetic analogues led to the final structure assignment for diol 2.

Full text of DOI:10.1021/np980098j

1400
J . Nat. Prod. 1998, 61, 1400-1403
P r en yla ted Ben zoic Acid s fr om Ra pa n ea m yr icoid es
Shelly B. Blunt, Tong-Bin Chen, and David F. Wiemer*
Department of Chemistry, University of Iowa, Iowa City, Iowa 52242-1294
Received March 16, 1998
Investigation of leaves from the shrub Rapanea myricoides led to the isolation of two diprenylated benzoic
acids. One was the known compound 5-carboxy-7-(3′′,3′′-dimethylallyl)-2-(1′-hydroxy-1′,5′-dimethylhex-
4′-enyl)-2,3-dihydrobenzofuran (1), while the other was assigned as the new diol 2 (3-(2′,3′-dihydroxy-
3′,7′-dimethyloct-6′-enyl)-4-hydroxy-5-(3′′,3′′-dimethylallyl)benzoic acid, myricoidiol). These compounds
were initially characterized through analysis of their spectroscopic data and comparison with some simpler
synthetic analogues led to the final structure assignment for diol 2.
Ta ble 1. 1H NMR and 13C NMR Data (δ) for Compounds
Leafcutter ants are considered to be major agricultural
pests over a geographical area ranging from Texas to
1 and 2.a
Argentina. Although many important crops suffer severe
defoliation from these ants, a wide variety of native
vegetation is left relatively unscathed.1 In the course of
our studies on plant chemical defenses against leafcutter
ants, a collection of plant species in diverse plant families
has been examined.2-5 Field and laboratory bioassays
indicated that the Costa Rican plant Rapanea myricoides
Schltdl. (Myrsinaceae) is seldom attacked by leafcutter
ants.1,6 As a result, we began investigating the secondary
chemistry of this plant. In this paper, we report the
isolation of two prenylated benzoic acids from R. myri-
coides extracts. Prenylated aromatic compounds isolated
from plant sources are common in the literature, including
some that are diprenylated benzoic acids.7-12 Members of
the diprenylated benzoic acid family include 3-geranyl-4-
hydroxy-5-(3′′,3′′-dimethylallyl)benzoic acid and 6-carboxy-
8-(3′′,3′′-dimethylallyl)-3R-hydroxy-2R-methyl-2-(4′-meth-
ylpent-3′-enyl)-3,4-dihydrobenzopyran.13 From R. myri-
coides, we isolated another known member of this family,
5-carboxy-7-(3′′,3′′-dimethylallyl)-2-(1′-hydroxy-1′,5′-dime-
thylhex-4′-enyl)-2,3-dihydrobenzofuran (1),13 and a novel
diol (2) that we have named myricoidiol. The structures
of compounds 1 and 2 were established by spectroscopic
methods, with the synthesis of various analogues employed
to clarify the structure of diol 2.
1
2
position
1H
13C
position
1H
7.71 sb
13C
1
2
1
2
130.2
129.8
4.69 dd
(9.4, 8.5)
3.21 m
7.75 br s
89.6
3
4
5
6
7
29.9
131.4
127.1
125.0
3
4
5
6
118.6
155.5
121.9
130.2
31.1
7.75 br s
7.73 sb
3.10 dd
123.1 1′
(16.8, 6.4)
2.84 dd
(16.8, 4.8)
3.92 dd
(6.4, 4.8)
8
162.4 2′
67.9
9
121.8 3′
73.7 4′
37.1 5′
21.9 6′
79.7
37.6
21.7
1′
2′
3′
1.63 m
2.16 m
5.10 tq
1.54 m
2.13 m
123.8
(7.0, 1.2)
4′
5.12 tq
(7.1, 1.3)
124.0 7′
132.3
5′
6′
7′
8′
1′′
2′′
133.2 8′
25.7 9′
17.6 10′
22.6
28.3 1′′
121.3 2′′
1.72 s
1.59 s
1.34 s
25.6
17.8
19.0
1.73 s
1.63 s
1.30 s
3.30 m
5.29 tq
3.31 d (7.2)
5.29 tq
(7.5, 1.3)
28.5
121.9
(7.3, 1.3)
3′′
4′′
5′′
132.2 3′′
25.7 4′′
17.8 5′′
132.8
25.8
17.8
1.74 s
1.69 s
1.73 s
1.67 s
CO2H
171.9 CO2H
171.3
a
b
J values are given in parentheses (Hz). Assignments may
be interchanged.
pounds (50 and 4 mg). The more abundant and less polar
of these compounds proved to be the prenylated benzoic
acid 1, which was previously reported as the methyl ester
from R. umbellata, but without defined stereochemis-
try.13,14 The second, more polar compound showed sets of
related resonances in its NMR spectra (Table 1) but
appeared to be a new member of this family.
Air-dried aerial parts of R. myricoides were steeped in
CHCl3 overnight, and the resulting CHCl3 extract was
subjected to dry column chromatography (CC) over silica
gel. The fraction that eluted with 30% hexanes in CH2Cl2
contained interesting downfield signals in its 1H NMR
spectrum and became the focus of further investigation.
This fraction was sequentially purified by dry CC, flash
CC, radial dispersion chromatography, and reversed-phase
HPLC. This sequence afforded two pure UV-active com-
The highest ion in the EIMS of compound 2 was observed
at m/z 358, corresponding to a molecular formula of
1
C
22H30O4 and eight degrees of unsaturation. Both the H
and 13C NMR spectra contained well-separated and easily
assigned resonances. Analysis of the 13C NMR and DEPT
spectra revealed the presence of five methyl groups, four
methylene carbons, two oxygenated sp3 carbons, one car-
boxylic acid, four sp2-hybridized methines, five sp2-hybrid-
* To whom correspondence should be addressed. Tel.: (319) 335-1365.
Fax: (319) 335-1270. E-mail: david-wiemer@uiowa.edu.
10.1021/np980098j CCC: $15.00
© 1998 American Chemical Society and American Society of Pharmacognosy
Published on Web 09/11/1998

Notes
J ournal of Natural Products, 1998, Vol. 61, No. 11 1401
Sch em e 1
be readily identified in the benzene ring, carbonyl group,
and two olefins. An epoxide ring spanning the oxygenated
methine and quaternary carbons of the side chain (C-2′ and
C-3′) would account for the remaining unsaturation. How-
ized quaternary carbons, and one sp2 carbon that was both
oxygenated and quaternary. Broad 1H NMR resonances
at δ 7.73 and 7.71 represented two aromatic hydrogens,
indicating a 1,3,4,5-tetrasubstituted aromatic ring, and the
intensity of this signal implied that the aromatic system
was symmetrical or very nearly so. With the exception of
the oxygenated aromatic carbon resonance, the 13C NMR
shifts of the aromatic carbons were almost identical to those
of the benzofuran 1, implying that the ring substituents
were similar but that this compound might incorporate a
phenolic -OH instead of the furan ether.
1
ever, if this were the case, both the H and 13C resonances
would be further upfield than those observed. An alternate
explanation could be based on assignment of the m/z 358
ion as an (M+ - H2O) peak for a diol such as compound 2,
suggesting a true molecular formula of C22H32O5 and only
seven degrees of unsaturation for the true natural product.
However, repeated MS analyses failed to detect an m/z 376
ion.
One of the aromatic substituents was identified as a
To distinguish between the two proposed structures,
synthesis of three simpler analogues was undertaken.
Methyl 4-hydroxybenzoate was alkylated with geranyl
bromide in the presence of sodium metal to give the known
geranylated product 3 (Scheme 1).9,15 The geranylated
phenol 3 then was subjected to epoxidation under Sharpless
conditions.16 Even though there is little precedent for
Sharpless epoxidation of prenylated phenols, this strategy
worked quite well. By variation of either the reaction
temperature or the workup procedures, we were able to
obtain three new oxidation products, the diol 4, the epoxide
1
prenyl group by comparison of the H resonances at δ 5.29,
3.31, 1.73, and 1.67, and 13C resonances at δ 132.8, 121.9,
28.5, 25.8, and 17.8, with those of compound 1 (Table 1). A
second olefinic resonance at δ 5.10 also was characteristic
of the olefinic hydrogen of a terpene. Along with a
methylene resonance at δ 2.16, methyl resonances at δ 1.59
and 1.72, and corresponding 13C NMR resonances (δ 132.3,
123.8, 25.6, 21.7, 17.8), these signals indicated that there
was an additional prenyl unit not directly connected to the
aromatic ring. An oxygenated methine was confirmed by
a resonance at δ 3.92 (J ) 16.8, 6.4 Hz) and the 13C NMR
signal at δ 67.9. This resonance was quite different in
chemical shift from those of the benzofuran 1 and 6-car-
boxy-8-(3′′,3′′-dimethylallyl)-3R-hydroxy-2R-methyl-2-(4′-
methylpent-3′-enyl)-3,4-dihydrobenzopyran, distinguishing
myricoidiol (2) from these other prenylated benzoic acids.
1
5, and the benzofuran 6. Comparison of the H NMR data
for these three compounds with that of the natural product
indicated that the natural product was indeed the diol 2.
The distinguishing 1H NMR resonances of the products
were the oxygenated methine hydrogen and the two ben-
zylic hydrogens. In diol 4, the methine doublet of doublets
was found at δ 3.92 (J ) 6.1, 5.1 Hz), and the benzylic
methylene hydrogens were at δ 3.10 (J ) 16.8, 5.9 Hz) and
2.83 (J ) 16.8, 6.1 Hz). These signals were considerably
different from the corresponding methines of epoxide 5 and
benzofuran 6 but compared nicely to those of the natural
product (Table 1). In epoxide 5, the methine resonated as
a doublet of doublets at δ 3.06 (J ) 9.8, 2.8 Hz) and the
benzylic hydrogens as doublet of doublets at δ 2.98 (J )
14.8, 2.8 Hz) and 2.85 (J ) 14.8, 9.8 Hz). The methine
resonance of the benzofuran 6 appeared at δ 4.72 (J ) 9.4,
8.8 Hz), with the two benzylic hydrogens at δ 3.26 (J )
15.9, 8.7 Hz) and δ 3.12 (J ) 15.9, 9.5 Hz). Analysis of the
13C NMR also supported this assignment. In the diol 4,
the methine carbon appeared at δ 67.8 and the oxygenated
quaternary carbon appeared at δ 79.7, correlating perfectly
The 1H resonance of the oxygenated methine was coupled
to resonances at δ 3.10 and 2.84, which were in turn
geminally coupled (J ) 16.8 Hz). These chemical shifts,
and that of the associated carbon (δ 31.1), established a
benzylic position adjacent to the oxygenated methine.
Selective INEPT data correlated the benzylic methylene
at δ 3.10 to the as yet unassigned oxygenated quaternary
carbon. These data suggested a partial structure corre-
sponding to ArCH2CH(O-)C(O-)RR′, with one of the alkyl
substituents identified as a methyl group corresponding
to a signal observed at δ 1.34 with a 13C NMR shift at δ
19.0 and the second alkyl substituent incorporating the
remaining prenyl chain.
Our initial analysis of the MS data suggested a com-
pound with eight degrees of unsaturation, and seven could

1402 J ournal of Natural Products, 1998, Vol. 61, No. 11
Notes
was allowed to cool to ∼25 °C, 10% HCl (10 mL) was added,
and the separated aqueous layer was extracted with Et2O (2
× 10 mL). The combined organic layers were washed with
H2O (15 mL), dried (MgSO4), and concentrated in vacuo. The
residue was purified by column chromatography (10% EtOAc/
hexanes) to give compound 3 (1.44 g, 37%) as a yellow oil: 1H
NMR δ 7.83 (m, 2H), 6.83 (d, J ) 8.9 Hz, 1H), 5.31 (tq, J )
7.1, 1.2 Hz, 1H), 5.07 (tq, J ) 6.8, 1.3 Hz, 1H), 3.87 (s, 3H),
3.40 (d, J ) 7.1 Hz, 2H), 2.10 (m, 4H), 1.78 (s, 3H), 1.68 (s,
3H), 1.60 (s, 3H); 13C NMR δ 167.3, 158.8, 138.9, 131.9, 131.8,
129.6, 126.9, 123.8, 122.3, 121.0, 115.4, 51.9, 39.7, 29.4, 26.4,
25.6, 17.6, 16.2.
with those of the natural product. The corresponding shifts
in epoxide 5 were δ 64.2 and 63.8, while the parallel
resonances of benzofuran 6 were δ 89.9 and 73.6. Interest-
ingly, the diol 4 did not give a molecular ion in repeated
MS experiments. Instead, it consistently gave an (M+
18) peak as the highest mass ion.
-
Confirmation of the structures of the synthetic products
was obtained by derivatization of diol 4 and epoxide 5 with
acetic anhydride in pyridine, giving the monoacylated
products 7 and 8.17 The methyl shift of the acetate 7 was
observed as a singlet at δ 2.10, demonstrating formation
of an aliphatic ester. In the aromatic acetate 8, the methyl
singlet of the acetate resonated farther downfield at δ 2.36,
differentiating it from the methyl singlet of acetate 7.
Furthermore, two exchangeable hydrogens, a phenol and
an alcohol hydrogen, were seen in the 1H NMR of com-
pound 7, but none was observed in the spectrum of acetate
8. Thus, formation of the acetate esters 7 and 8 made clear
that compounds 4 and 5 were the diol and epoxide
respectively, and the correspondence between the spectra
for compounds 4 and 2 confirmed the structure proposed
for myricoidiol.
Diol 4. To a solution of compound 3 (0.64 g, 2.2 mmol) in
CH2Cl2 (20 mL, distilled from CaH2) at -23 °C was added
L-(+)-diethyl tartrate (0.52 g, 1.1 mmol) followed by Ti(O-i-
Pr)4 (0.75 g, 1.2 mmol). This solution was stirred for 5 min
before addition of 3.3 M t-BuOOH in toluene (1.5 mL, 2.2 mol),
and the resulting solution was then stored in a freezer at ∼20
°C. After 24 h, the flask was placed in a -23 °C bath, and
10% aqueous tartaric acid (5 mL) was added with stirring. The
cold bath was removed after 30 min, and the mixture was
stirred until the aqueous layer melted and became clear. The
aqueous layer was separated, and the organic layer was
washed with H2O, dried (Na2SO4), and concentrated in vacuo.
The resulting oil was then diluted with Et2O (15 mL) and
cooled to 0 °C, and 1 N NaOH (6 mL) was added. After the
reaction mixture was stirred for 30 min, the ether layer was
washed with brine, dried (Na2SO4), and concentrated in vacuo.
The residual oil was purified by column chromatography (25%
EtOAc/hexanes) to give the desired product 4 as a pale yellow
oil (0.13 g, 68% yield based on recovered starting material):
1H NMR δ 7.79, (m, 2H), 6.85 (d, J ) 9.1 Hz, 1H), 5.08 (tq, J
) 7.1, 1.4 Hz, 1H), 3.92 (dd, J ) 6.1, 5.9 Hz, 1H), 3.87 (s, 3H),
3.10 (dd, J ) 16.8, 5.1 Hz, 1H), 2.83 (dd, J ) 16.8, 6.1 Hz,
1H), 2.10 (m, 2H), 1.66 (s, 3H), 1.58 (s, 3H), 1.50 (m, 2H), 1.34
(s, 3H); 13C NMR δ 166.9, 157.1, 132.3, 132.2, 129.5, 123.7,
122.4, 118.9, 117.2, 79.7, 67.8, 51.8, 37.3, 30.9, 25.6, 21.6, 19.2,
17.6; HRFABMS m/z [M - H2O + H]+ 305.1783 (calcd for
Through synthesis of the prenylated benzoic acid deriva-
tives 4-6, we were able to establish the structure of diol
2. The directing effect of the phenol in the Sharpless
epoxidation reaction appears to be the first example of this
kind. Unfortunately, this epoxidation reaction showed no
stereoselectivity, giving a racemic mixture as proven by
subsequent formation of O-methyl mandelate esters. Thus,
the general structure of myricoidiol can be assigned as
shown in structure 2, but the absolute stereochemistry of
this compound must still be addressed.
Exp er im en ta l Section
Gen er a l Exp er im en ta l P r oced u r es. Flash chromatog-
raphy was carried out on Baker silica gel with 40 µm average
particle diameter. NMR spectra (1H at 300 MHz and 13C at
75 MHz) were recorded with CDCl3 as solvent and (CH3)4Si
(1H) or CDCl3 (13C, 77.0 ppm) as internal standards, unless
otherwise noted. Both low- and high-resolution mass spectra
were obtained at an ionization potential of 70 eV; only selected
ions are reported here.
C
18H25O4, 305.1753).
Ep oxid e 5. According to the procedure described for
preparation of compound 4, compound 3 (99 mg, 0.34 mmol)
was treated with L-(+)-diethyl tartrate (130 mg, 0.63 mmol),
Ti(O-i-Pr)4 (160 mg, 0.57 mmol), and t-BuOOH (0.2 mL, 0.72
mmol) at 0 °C. After treatment with saturated aqueous
NaHCO3, standard workup and purification by column chro-
matography (25% EtOAc/hexanes) gave compound 5 as a pale
yellow oil (51 mg, 48%): 1H NMR δ 7.85 (m, 2H), 6.94 (d, J )
8.7 Hz, 1H), 5.06 (tq, J ) 7.2, 1.3 Hz, 1H), 3.88 (s, 3H), 3.06
(dd, J ) 9.8, 2.8 Hz, 1H), 2.98 (dd, J ) 14.9, 2.8 Hz, 1H), 2.85
(dd, J ) 14.9, 9.8 Hz, 1H), 2.09 (dt, J ) 7.6, 7.6, Hz, 2H), 1.67
(s, 3H), 1.60 (s, 3H), 1.50 (m, 2H), 1.49 (s, 3H); 13C NMR δ
167.0, 160.1, 132.6, 132.4, 130.7, 124.1, 123.0, 122.2, 117.0,
64.2, 63.8, 51.8, 38.3, 31.7, 25.6, 23.5, 17.6, 16.8; HRFABMS
m/z [M + H]+ 305.1748 (calcd for C18H25O4, 305.1753).
Ben zofu r a n 6. According to the procedure described for
preparation of compound 4, compound 3 (77 mg, 0.27 mmol)
was treated with L-(+)-diethyl tartrate (94 mg, 0.7 mmol), Ti-
(O-i-Pr)4 (94 mg, 0.49 mmol), and t-BuOOH (0.2 mL, 0.72
mmol) at 25 °C. Standard workup and purification by flash
column chromatography (25% EtOAc/hexanes) gave compound
6 as a pale yellow oil (41 mg, 51%): 1H NMR δ 7.85 (m, 2H),
6.78 (d, J ) 9.0 Hz, 1H), 5.12 (tq, J ) 7.0, 1.3 Hz, 1H), 4.72
(dd, J ) 9.4, 8.8 Hz, 1H), 3.87 (s, 3H), 3.26 (dd, J ) 15.9, 8.7
Hz, 1H), 3.12 (dd, J ) 15.9, 9.5 Hz, 1H), 2.10 (m, 2H), 1.69 (s,
3H), 1.63 (s, 3H), 1.50 (m, 2H), 1.31 (s, 3H); 13C NMR δ 166.9,
163.6, 132.3, 131.0, 127.6, 126.7, 124.0, 122.8, 108.8, 89.9, 73.6,
51.8, 36.9, 29.7, 25.7, 22.8, 21.9, 17.7; HREIMS m/z [M]+
304.1684 (calcd for C18H24O4, 304.1675).
P la n t Ma ter ia l. Leaves of R. myricoides were collected
near Rincon de la Vieja, Costa Rica. The leaves were air-dried
and then chopped in a Waring blender before storage in plastic
bags. Voucher specimens have been deposited in the J erome
J . Howard collection.
Extr a ction a n d Isola tion . The R. myricoides leaves (150
g) were steeped in CHCl3 for 24 h and then concentrated in
vacuo. The resulting residue (15 g) was partitioned between
30% CH2Cl2/hexanes and water. The organic extract was
further purified by dry column chromatography eluting with
50% EtOAc/hexanes, followed by a 85% MeOH/H2O Sep-Pak
purification and then radial dispersion chromatography (5-
40% EtOAc/hexanes/1% AcOH). Radial dispersion chroma-
tography (5-40% EtOAc/hexanes/1% AcOH) yielded pure
compound 1 (50 mg) and crude myricoidiol (2). Pure diol 2 (4
mg) was obtained after final purification by HPLC with an
80-100% MeOH/H2O gradient.
Myr icoid iol (2). colorless oil; [R]25 -12.8°(CHCl3, c 0.2);
D
1H NMR see Table 1; 13C NMR see Table 1; EIMS m/z [M+
H2O] 358.
-
Meth yl 3-Ger a n yl-4-h yd r oxyben zoa te (3).9 To a solu-
tion of methyl 4-hydroxybenzoate (2.05 g, 13.5 mmol) in
anhydrous Et2O (30 mL) were added small pieces of Na (0.9
g, 39.1 mmol). The mixture was stirred for 3 h at ∼25 °C
under nitrogen, and then geranyl bromide (3 mL, 15.1 mmol)
was added dropwise. The resulting mixture was heated at
reflux for 48 h until all sodium had disappeared. The solution
Aceta te 7. To a solution of compound 4 (38 mg, 0.12 mmol)
in pyridine (10 mL) was added acetic anhydride (60 µL), and
the resulting solution was heated at 80 °C for 18 h. The
solvent was removed in vacuo, and the resulting residue was
purified by flash column chromatography (20% EtOAc/

Notes
J ournal of Natural Products, 1998, Vol. 61, No. 11 1403
Refer en ces a n d Notes
hexanes) to afford the acetate 7 as a colorless oil (37 mg,
85%): 1H NMR δ 7.80 (m, 3H, 1 exchangeable), 6.86 (d, J )
8.6 Hz, 1H), 5.12 (dd, J ) 5.1, 5.0 Hz, 1H), 5.04 (tq, J ) 7.1,
1.4 Hz, 1H), 3.87 (s, 3H), 3.16 (dd, J ) 17.3, 5.0 Hz, 1H), 2.82
(dd, J ) 17.3, 5.2 Hz, 1H), 2.24 (br s, 1H, exchangeable), 2.12
(m, 2H), 2.07 (s, 3H), 1.65 (s, 3H), 1.60 (m, 2H), 1.57 (s, 3H),
1.33 (s, 3H); 13C NMR δ 170.4, 166.9, 156.9, 132.3, 131.8, 129.5,
123.3, 122.3, 118.2, 117.2, 77.9, 69.3, 51.8, 37.1, 27.9, 25.6, 21.5,
21.0, 20.0, 17.5; HRFABMS m/z [M - H2O + Na]+ 369.1679
(calcd for C20H26O5Na, 369.1678).
Aceta te 8. The epoxide 5 (24 mg, 0.08 mmol) was treated
with acetic anhydride (40 µL) in pyridine (10 mL) as described
for compound 7 to obtain the aromatic acetate 8 in quantitative
yield (27 mg): 1H NMR δ 8.02 (d, J ) 2.0 Hz, 1H), 7.96 (d, J
) 8.4, 2.0 Hz, 1H), 7.43 (d, J ) 8.5 Hz, 1H), 5.03 (tq, J ) 7.2,
1.3 Hz, 1H), 3.91 (s, 3H), 2.94 (dd, J ) 5.9, 5.8 Hz, 1H), 2.88
(dd, J ) 14.7, 6.1 Hz, 1H), 2.76 (dd, J ) 14.6, 5.6 Hz, 1H),
2.36 (s, 3H), 2.07 (m, 2H), 1.63 (s, 3H), 1.58 (s, 3H), 1.45 (m,
2H), 1.37 (s, 3H); 13C NMR δ 168.8, 166.3, 152.7, 132.0, 131.9,
130.6, 129.4, 128.1, 123.4, 122.7, 62.2, 61.0, 52.2, 38.5, 29.8,
25.6, 23.7, 21.0, 17.6, 16.8; HRFABMS m/z [M + H]+ 347.1833
(calcd for C20H27O5, 347.1858).
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Ack n ow led gm en t. We thank Dr. J erome J . Howard
(University of New Orleans) for collection of the plant material
at Rincon de la Vieja, the Missouri Botanical Gardens for
definitive identification of the plant species, and the National
Park Service of Costa Rica for their assistance with our
research.
(15) Bouzbouz, S.; Kirschleger, B. Synthesis 1994, 714-718.
(16) Katsuki, T.; Sharpless, K. B. J . Am. Chem. Soc. 1980, 102, 5974-
5976.
(17) Zhdanov, R. I.; Zhenodarova, S. M. Synthesis 1975, 222-245.
NP980098J