Con figurative correlation and conformational analysis of strictosidine and vincoside derivatives

Article abstract of DOI:10.1021/np990150r

On the basis of the configuration of C-15 of the secologanin unit, using detailed NMR analysis, the configuration of C-3, the solution conformation around C-14, and the glucosidic bridge, as well as those of the dihydropyran and tetrahydropyridine rings, were determined in the vincosamide and strictosamide derivatives 4b and 5b. The stereochemical analysis was extended by chemical correlation to the 4-benzylated strictosidine and vincoside derivatives 3c and 3d. Experimental proof was presented for the interpretation of the 'anomalous' chemical shift of acetylated strictosamide derivatives.

Full text of DOI:10.1021/np990150r

1492
J . Nat. Prod. 1999, 62, 1492-1499
Con figu r a tive Cor r ela tion a n d Con for m a tion a l An a lysis of Str ictosid in e a n d
Vin cosid e Der iva tives†
AÄ gnes Patthy-Luka´ts,‡ AÄ kos Kocsis,‡ La´szlo´ F. Szabo´,*,‡ and B. Poda´nyi§
Institute of Organic Chemistry, Semmelweis University of Medicine, Ho˜gyes u. 7, H-1092 Budapest,
and Chinoin Pharmaceutical and Chemical Works, Ltd., To´ utca 1-5, H-1045 Budapest, Hungary
Received April 5, 1999
On the basis of the configuration of C-15 of the secologanin unit, using detailed NMR analysis, the
configuration of C-3, the solution conformation around C-14, and the glucosidic bridge, as well as those
of the dihydropyran and tetrahydropyridine rings, were determined in the vincosamide and strictosamide
derivatives 4b and 5b. The stereochemical analysis was extended by chemical correlation to the
4-benzylated strictosidine and vincoside derivatives 3c and 3d . Experimental proof was presented for
the interpretation of the “anomalous” chemical shift of acetylated strictosamide derivatives.
In the presence of the enzyme strictosidine synthase, the
coupling reaction of tryptamine (1a ) and secologanin (2a )
gives strictosidine (3a ) with complete stereoselectivity.2
However, in the absence of the enzyme, both strictosidine
(3a ) and vincoside (3b) are formed with low stereoselec-
tivity.3 The configuration of the new center of chirality C-3
has been a subject of controversy;4 however, in the vinco-
side series this was determined unequivocally by X-ray
diffraction analysis of O′,O′,O′,O′-tetraacetyl-4-(4′′-bro-
mobenzyl)vincoside (3d ), prepared by direct coupling of Nb-
4′-bromobenzyl-tryptamine (1b) and O′,O′,O′,O′-tetraace-
tylsecologanin (2b).5 The coupling reaction gave exclusively
the vincoside derivative, and isomeric strictosidine deriva-
tives could not be obtained in other ways in appropriate
crystalline form. Previously, the stereochemistry of C-3 in
the strictosidine derivatives was derived by complicated
multistep chemical correlations that involved the danger
of unexpected configurational changes. Similar uncertain-
ties were experienced in the case of the dolicanthoside and
isodolicanthoside (4-methyl derivatives of strictosidine and
vincoside) during the study of their CD spectra.6,7 There-
fore, in the strictosidine series, a rigorous proof of the
configuration of C-3 was not possible for a long time.
Recently, in our laboratory, this configuration has been
proved by detailed NMR studies.8 The confusion in the
4-methyl derivatives was eliminated by reinterpretation of
the CD spectra.9 It was still necessary, however, to place
the stereochemistry of these terpenoid glycosides on a firm
experimental base. The aim of the present work was to
extend our previous results to other strictosidine and
vincoside derivatives by preparative configurative correla-
tions, as well as to demonstrate their conformations in
solution.
the lactam series, the stereochemistry could be proved
unequivocally by NMR spectroscopy; 3d was transformed
into O′,O′,O′,O′-tetraacetyl-18,19-dihydrovincosamide (4b,
84% yield) by catalytic hydrogenation involving saturation
of the vinyl group, removal of the 4-bromobenzyl group,
and spontaneous lactamization.
2. As O′,O′,O′,O′-tetraacetyl-4-(4′′-bromobenzyl)stricto-
sidine (3c) could not be prepared by direct coupling, it was
prepared from strictosidine (3a )8 by alkylation with 4-bro-
mobenzyl bromide and subsequent acetylation (48% yield).
After removal of the 4-bromobenzyl and saturation of the
vinyl group, lactamization in aqueous sodium carbonate
solution at 70 °C gave O′,O′,O′,O′-tetraacetyl-18,19-dihy-
drostrictosamide (5b, 84% yield).
3. For rigorous correlation it was obviously necessary to
prepare 4b and 5b from starting materials that had been
formed simultaneously in the same reaction mixture.
Therefore, by a slight modification of the method of
Battersby et al.,3 tryptamine (1a ) and secologanin (2a ) were
reacted to obtain strictosidine (3a ) and vincoside (3b) in
an approximately 1:1 ratio. However, in the reaction
mixture, vincoside had already spontaneously lactamized
to vincosamide (4a ) and precipitated.3 After filtration and
recrystallization, pure 4a was obtained (27% yield calcu-
lated from 2a ).8 It was acetylated and hydrogenated to the
same 4b (47% yield) that was previously prepared accord-
ing to point 1.
4. The mother liquor of the coupling reaction of point 3
afforded, after evaporation of the solvent, strictosidine (3a ,
36% yield from 2a ), which was lactamized in aqueous
sodium carbonate at 70 °C to strictosamide (5a , 80% yield).3
This compound was acetylated and hydrogenated to the
same 5b (75% yield) that was previously prepared accord-
ing to point 2.
Resu lts a n d Discu ssion
These easy transformations under mild reaction condi-
tions excluded the epimerization at any center of chirality.
In the stereochemical analysis,10 the main problem was to
determine the dominant conformation around C-14. In both
series, the Newman projections of the nine possible con-
formers around bonds C-3-C-14 and C-14-C-15 (11-13,
The reaction sequences are shown in Scheme 1. Several
conclusions were made and are enumerated as follows:
1. The starting point of the correlations was the result
of the X-ray diffraction analysis of O′,O′,O′,O′-tetraacetyl-
4-(4′′-bromobenzyl)vincoside (3d ), which was prepared by
the slightly modified method of Hutchinson et al.5 As in
1
21-23, 31-33) may be characterized by the vicinal H-
1H coupling constants according to the synclinal (sc) and
antiperiplanar (ap) positions of the hydrogens attached to
C-3, C-14, and C-15 in both series (Table 1 and Figure 1).
In the R series, the R configuration of C-3 (H-3â in the
usual representation) was derived according to the result
* To whom correspondence should be addressed. Tel.: 36 12 17 12 95.
E-mail: szalasz@szerves.sote.hu.
† Part
6 in the series Chemistry of Secologanin. For Part 5, see
Ka´rolyha´zy et al.1
‡ Semmelweis University of Medicine.
§ Chinoin Pharmaceutical and Chemical Works, Ltd.
10.1021/np990150r CCC: $18.00
© 1999 American Chemical Society and American Society of Pharmacognosy
Published on Web 09/18/1999

Strictosidine and Vincoside Derivatives
J ournal of Natural Products, 1999, Vol. 62, No. 11 1493
Sch em e 1. Configurative Correlation of Strictosidine and Vincoside Derivatives
Ta ble 1. Relative Orientation of H-3 and H-15 to H-14proR and H-14proSa
H-3
H-15
H-3
H-15
H-3
H-15
H-14
H-3
H-15
H-3
H-15
H-3
H-15
S11
S21
S31
S12
S22
S32
S13
S23
S33
R11
R21
R31
R12
R22
R32
R13
R23
R33
ap
sc
sc
ap
ap
sc
ap
sc
ap
sc
sc
sc
proR
proS
sc
ap
ap
sc
sc
ap
sc
ap
sc
ap
sc
sc
sc
ap
sc
ap
sc
ap
ap
sc
sc
ap
sc
sc
proR
proS
ap
sc
ap
sc
ap
sc
sc
ap
ap
sc
sc
sc
sc
sc
sc
ap
sc
sc
ap
sc
sc
sc
sc
sc
proR
proS
sc
sc
ap
sc
sc
sc
sc
ap
sc
sc
sc
sc
a
The letters ap and sc indicate antiperiplanar and synclinal orientation of the appropriate H’s, respectively.
of the X-ray diffraction analysis,5 while in the S series, the
conformers were derived by preliminary supposition (based
on our previous analysis of strictosidine8) of the opposite
S configuration at C-3 (H-3R). Each C-14 conformer may
exist in four ring conformers, according to the negative or
positive half-chair conformation of the dihydropyran and
tetrahydropyridine rings, respectively (NN, NP , P N, P P ).
Further issues were to determine the axial (A) or equatorial
(E) position of the eventual benzyl group and the confor-
mation around the glucosidic oxygen bridge. To facilitate
the analysis, stereostructures were constructed by the
ALCHEMY II program12 for the possible conformers.
Detailed analysis of the NMR data gave the following
results for the stereostructures of the intermediates and
final products in solution.
The stereostructure of O′,O′,O,′O′-tetraacetyl-18,19-di-
hydrovincosamide (4b) and -dihydrostrictosamide (5b).
Unlike the tetracyclic derivatives, in the pentacyclic lac-
tams the number of possible conformers around C-14 is
limited, because in each series there are only two conform-
ers in which N-4 and C-22 are sufficiently close for
cyclization. These are R12 and R33 for 4b, and S13 and
S31 for 5b. For these conformers, the vicinal coupling
constants of protons H-3, H-14, and H-15 were estimated
according to the dihedral angles of the appropriate pairs
of C-H bonds. Because the four possible coupling patterns
are different, comparison of the expected and measured
coupling constants unequivocally established the conforma-
tion around C-14 (Table 2). In 4b, H-14proS had large
coupling constants (12.5 and 13.0 Hz), whereas H-14proR
was observed to have small coupling constants (3.6 and 3.5
Hz) with the vicinal protons H-3 and H-15, respectively.
This pattern of J values is appropriate only for conformer
R12 and establishes the axial orientation of H-3 and H-15
on the lactam ring. Conformer R33 would require small
coupling constants for both H-14 protons with each of the
vicinal protons. In amide 5b, H-3 had small coupling
constants with H-14proR (2.8 Hz) and H-14proS (5.5 Hz).
However, H-15 had a large coupling constant (13.5 Hz) with
H-14proS and small one (4.9 Hz) with H-14proR. This
coupling pattern corresponds to the conformer S31 and
established the equatorial position of H-3 to the lactam
ring. S13 would require large coupling constant between
H-14proR and H-3, rather than between H-14proS and
H-15. It should be noted that R12 and S31 are the only
two C-14 conformers where the lactam ring can take up a
half-chair conformation.
In consideration of the established S configuration of C-5
in loganin13 (analogous to C-15 in the monoterpenoid indole
alkaloids) as well as the independent determination of C-15

1494 J ournal of Natural Products, 1999, Vol. 62, No. 11
Patthy-Luka´ts et al.
F igu r e 1. Newman formulas of the conformers around C-14. The letters ap and sc indicate antiperiplanar and synclinal orientation of the appropriate
Hs, respectively.
Ta ble 2. Comparison of Expected and Determined H-H
Coupling Constants (J ) around C-14
corresponds to the steric pattern R12NN, H-3 is in a â-axial
orientation to the lactam ring, and C-2 takes the R
equatorial orientation. The â equatorial orientation of C-5
to the lactam ring is in agreement with the data given in
the discussion regarding the conformation of the tetrahy-
dropyridine ring. The trans diequatorial attachment of this
ring to the lactam ring endows the pentacyclic ring system
with a flat shape. In 5b, which corresponds to the steric
pattern S31NP , and in which H-3 has the R-equatorial
orientation to the lactam ring, C-2 should assume a â-axial
position, and C-5 will necessarily be in the â-equatorial
orientation. Cis attachment of the tetrahydropyridine ring
to the lactam ring forces the indole ring system into a
position approximatively perpendicular to the other part
of the aglycon unit.
determined J
(in Hz)
expected J in
S31 R12
interacting H-s
S13
R33
4b
5b
H-3-H-14proR
H-3-H-14proS
large small small small
small small large small
H-15-H-14proR small small small small
H-15-H-14proS small large large small
2.8
5.5
4.9
3.6
12.5
3.5
13.5
13.0
in 3d ,5 these results also establish for 4b the R (H-3â) and
for 5b the S (H-3R) configuration of C-3. They are in
agreement with the X-ray diffraction analysis in the R
series,5 and further confirm our previous determination in
the S series.9
The latter statement was further supported by the strong
diamagnetic shift of one of the acetyl methyl signals in 5b
(δ 1.20 ppm vs 2.07, 1.99, 1.88 ppm for the others), which
gave the possibility to determine simultaneously the
conformation around the glucosidic O bridge. This “anoma-
lous” chemical shift is well-known in all acetylated stric-
tosamide derivatives since the first publication3 on stric-
tosidine, but was not interpreted until recently. In 5b, the
long-range carbon-proton coupling of this H-methyl and
H-2′ with the same carbonyl carbon was detected by
selective INEPT experiments15 that established that this
acetyl group was attached to O-2′ of the â-D-glucopyranosyl
unit. The same conclusion was made by Aimi et al.16 in 5a
on the basis of HMBC measurements. In addition, in the
NOESY spectrum of 5b, cross-peaks of H-9 and H-11 with
H-methyl were detected. This provides the first experi-
mental proof for the steric proximity of the methyl group
to the indole ring. Therefore the “anomalous” shift results
as a consequence of the diamagnetic effect of the ring-
current of the aromatic indole ring. This proximity is
strongly dependent on the conformation around the glyco-
sidic oxygen bridge. In our previous paper on the stereo-
chemical analysis on strictosidine,8 experimental and
theoretical arguments were presented in favor of the most
stable conformer around the glycosidic O bridge. In this
conformer one of the nonbonding orbitals of the O bridge
with the bond O-17-C-21, and the other with bond C-1′-
O-5′ is in an ap position; that is, a double σ-conjugation is
stabilizing this conformer. Model studies indicated that the
The conformation of the dihydropyran ring was deter-
mined from the vicinal coupling constant J 20,21, which has
3
a small value in both amide compounds 4b (1.9 Hz) and
5b (1.8 Hz). With respect to the configurations in secolo-
ganin, this value is characteristic for the trans diequatorial
relationship of the two protons. This is possible only if the
conformation of the ring is negative. Moreover, it involves
the â-orientation of H-15 in both amides, as well as the â
orientation in 4b and the R orientation in 5b of H-3 in the
usual representation.
The conformation of the tetrahydropyridine ring was
established from the interpretation of the NOESY spec-
trum. H-3 displayed a cross-peak with one of the H-5
protons in both amides. The interacting protons should be
in a cis diaxial relationship that concerns H-5â in amide
4b and H-5R in amide 5b. In the first case this indicates a
negative and in the second case a positive conformation of
the tetrahydropyridine ring. These conformations were
further confirmed by the observation that the other C-5
proton, that is, H-5R in 4b and H-5â in 5b, had a
substantially higher δ value than its geminal partner (δ
5.14 vs 2.88, 5.02 vs 3.03, respectively). This strong
paramagnetic shift is due to the anisotropic effect of the
carbonyl group, which can be effective only in an equatorial
orientation of the appropriate proton to the tetrahydropy-
ridine ring.14
According to this analysis, the three-dimensional shape
of 4b and 5b can easily be seen (Figure 2). In 4b, which

Strictosidine and Vincoside Derivatives
J ournal of Natural Products, 1999, Vol. 62, No. 11 1495
F igu r e 2. Three-dimensional structures of 3c, 3d , 4b, and 5b (R ) acetyl).
2′-acetoxy group can approach the indole ring system
perpendicularly only in this conformation. Although this
acetyl group has some conformation mobility around the
O-acetyl bond, its preferred, least crowded orientation
closest to the indole ring is shown in Figure 2. In the
spectrum of the acetylated vincosamide derivatives, no
“anomalous” shift was expected or observed, because the
indole ring system is far away from any of the acetyl groups
of the â-D-glucopyranosyl unit in any conformation. How-
ever, as the double σ-conjugation is independent of the
other parts of the molecule, it may be supposed that the
same conformation around the O bridge is dominant in all
glucosidic secologanin derivatives.
the tetrahydropyridine ring. In both compounds, the pro-
tons of the benzyl-CH2 group gave cross-peaks with H-3
and with the equatorial H-5 proton. This means that the
benzyl group in 3c has an R-axial orientation and in 3d
has a â-axial orientation. In conclusion, the bulky ligands
of C-3 and N-4 in both derivatives are in a trans diaxial
position. Moreover, it should be noted that in both deriva-
tives the benzyl protons gave NOE cross-peaks with the
axial H-6 proton. This suggested an axial position of the
benzyl group in which the C(H2)-benzyl-C-1′′ bond was
ap to the N-4-C-5 bond.
In the tetracyclic bases, the conformation around C-14
is not fixed by cyclization; therefore, none of the nine
staggered conformers around C-14 may be disregarded a
priori. The situation is simpler in 3d . One of the H-14
atoms has a large coupling constant with H-3, and the other
with H-15, which established the ap orientation of the
appropriate H atoms. R11 and R22 are the only two
conformers corresponding to this coupling constant pattern.
The distinction between these conformers was made by
observing a medium-strong cross-peak between H-3 and
H-20 in the NOESY spectrum of 3d , which suggested a
short, through-space distance between them. According to
measurements on the computer-generated structures, these
two protons are very close (1.9 Å) in conformer R11, which
is the favored one. In R22 the two protons would be too
far (4.7 Å) apart for a NOE to be observed.
The stereostructures of O′,O′,O′,O′-tetraacetyl-4-(4′′-bro-
mobenzyl)strictosidine (3c) and -vincoside (3d ) were con-
sidered next. The identical configuration of C-3 in the
tetracyclic bases and the corresponding pentacyclic lactams
was proved by transformation of 3c into 5b, and of 3d into
4b in two steps and under mild conditions. Accordingly,
C-3 has the S configuration in 3c (H-3R) and the R
configuration in 3d (H-3â). In both derivatives the small
3
value of J 20,21 indicated the negative conformation of the
dihydropyran ring.
The conformation of the tetrahydropyridine ring was
derived from the NOESY spectrum. In both compounds,
one of the H-14 protons gave a cross-peak with one of the
H-5 protons. This is possible only if C-14 and the interact-
ing H-5 are in a cis diaxial orientation. According to the
established configuration of C-3, orientation of C-14 is â
in 3c and R in 3d ; therefore, the interacting H-5 proton
(H-5â in the former and H-5R in the latter compound)
should have axial orientation, which is possible only in 3c
in the negative, and in 3d in the positive conformation of
In 3c the situation is more complicated; therefore, the
carbon-proton coupling constants of this derivative were
measured by an improved HETLOCK pulse sequence.17
They were used together with 1H-1H coupling constants
and NOE observations to determine the dominant confor-
mation. The moderately large coupling constant (8.7 Hz)

1496 J ournal of Natural Products, 1999, Vol. 62, No. 11
Patthy-Luka´ts et al.
has the same effect on the coupling constants.22 In this
case, the measured J C3,H14 coupling constants are -6.0 and
Ta ble 3. Comparison of Torsion Angles around C-14 with the
Coupling Constants (J )
2
-2.6 Hz. In the S22d conformation, both hydrogens of the
C-14 methylene group are sc to N-4, so that similar
coupling constants should be expected. However, in S12d ,
the H-14proR is in the sc orientation, while H-14proS is
in an ap orientation to N-4. Therefore, the measured data
suggested that S12d is the dominant conformer of 3c.
Consequently, the signals showing -6.0 Hz and -2.6 Hz
coupling constants with C-3 can be assigned to the H-14proR
and H-14proS atoms, respectively. In agreement with this
assignment and the dominance of the S12d conformation,
the signal assigned to the H-14proR shows a 8.7 Hz
coupling constant due to the spin-spin interaction with
H-3.
The NOESY spectrum was also in agreement with this
structure. For the evalution of the results, the cross-peak
intensity corresponding to a hypothetical atomic pair
distance of 3.3 Å was calculated by the two-spin ap-
proximation method and by using the NOE of the H-1′-
H-5′ interaction (2.5 Å) as a reference value. The volume
of all cross-peaks was integrated, and the higher or lower
values compared to the reference integral were considered
to be strong or weak. The distances of the atomic pairs
having unambiguously defined orientation in the S12d
conformer were compared with the cross-peak intensities.
The through-space interatomic distances of the model
corresponding to strong and weak cross-peaks lay in the
1.8-2.6 Å and 2.6-3.7 Å regions, respectively.
In summary, the conformation of the dihydropyran ring
is negative in both compounds 3c and 3d ; that of the
tetrahydropyridine ring is negative in 3c and positive in
3d . The favored conformation around the methylene bridge
is S12d in 3c, and R11 in 3d . Consequently, the stereo-
chemical notation of 3c is S12d NN; that of 3d is R11NP .
The three-dimensional shapes of 3c and 3d are shown in
Figure 2.
It is hoped that the results described here will assist in
the interpretation of further details of the chemistry of
secologanin, which will be the subject of subsequent papers,
and that the stereochemical problems of this important
class of alkaloids have been placed on a firm experimental
base.
in degrees, calcd for
measd J
torsion angle of
S12d
S22d
(in Hz)
H-3-C-3-C-14-H-14proR
H-3-C-3-C-14-H-14proS
H-3-C-3-C-14-C-15
+166.0
-74.6
+46.6
+74.6
-166.0
-44.8
-130.2
+110.0
-11.0
-45.2
+74.1
3J H3,H14R
3J H3,H14S
8.7
4.2
3.4
5.8
4.0
5.6
3J H3,C15
H-15-C-15-C-14-H-14proR -130.1
H-15-C-15-C-14-H-14proS +110.0
3J H14R,H15
3J H14S,H15
3J C3,H15
H-15-C-15-C-14-C-3
N-4-C-3-C-14-H-14proR
N-4-C-3-C-14-H-14proS
-11.0
+46.1
+165.5
2J C3,H14R -6.0
2J C3,H14S
-2.6
of H-3 with one of the H-14 atoms indicated one (ap-
proximately) ap orientation and excluded conformers of the
S3 series (S31, S32, S33), where both H-14 atoms should
have sc orientation to H-3. H-15 has one small coupling
constant to one of the H-14 protons (4.0 Hz). However, the
coupling constant of H-15 to the other H-14 gave an
ambiguous value (5.8 Hz) that corresponded to neither a
clear sc, nor a clear ap orientation of the appropriate
hydrogens and suggested a distorted conformation around
the C-14-C-15 bond. To find the most advantageous
conformation, in the computer-generated molecular models,
H-14proR in the S1 series and H-14proS in the S2 series
were kept in an ap orientation, and the secologanin subunit
was turned around the C-14-C-15 bond by 360°, with
continuous measurement of the through-space interatomic
distances between the appropriate atoms of the secologanin
and tryptamine subunits. In both series, only a relatively
narrow torsion angle interval (between -20° and +5°
around C-3-C14-C-15-H-15) was found in which no
serious internal steric interferences would be expected.
Finally, the torsion angle around C-3-C-14 was also
slightly modified. As these conformers can be derived from
S12 and S22 by a rotation of less than 60° around C-3-
C-14 and C-14-C-15, respectively, the “distorted” struc-
tures remain in the original segment and are referred as
the S12d and S22d conformers. The characteristic torsion
angles of the two conformers and the value of the measured
coupling constants that are influenced by these dihedral
angles are shown in Table 3. The expected values of the
3
3
coupling constants J H14R-H15 and J H14S,H15 in these struc-
tures were calculated using a modified Karplus-type equa-
tion.18 The tabulated values of 6.1 and 2.6 Hz are in good
agreement with the measured coupling constants 5.8 and
Exp er im en ta l Section
3
4.0 Hz, respectively. The expected J C3,H15 coupling constant
Gen er a l Exp er im en ta l P r oced u r es. NMR spectra were
recorded on a Bruker AM-200 spectrometer at 200 MHz (1H)
and 50 MHz (13C), on a Bruker AC-250 spectrometer at 250
MHz (1H) and 62 MHz (13C), on a Bruker AC-400 spectrometer
at 400 MHz (1H) and 100 MHz (13C), or on a Bruker DRX-400
spectrometer at 400 MHz (1H) and 100 MHz (13C). TMS was
used as the chemical-shift reference. COSY, NOESY, and
selective TOCSY spectra were measured with the standard
Bruker microprograms of the DISNMR or the XWINNMR
software. In the phase-sensitive NOESY spectra a 600-ms
mixing time was used. The cross-peak intensities were cate-
gorized as strong, medium, or weak by visual inspection of the
spectra for all compounds except for 3c, where the volumetric
integration by the XWINNMR program was applied. The
selective TOCSY spectra were measured with a 270° Gaussian-
shaped selective excitation pulse, 20-, 40-, 70-, and 100-ms
spin-lock times. Selective INEPT spectra were measured with
10-ms selective rectangular 90° 1H pulses, the delays were
optimized for 7-Hz couplings.
for these conformations was calculated to be 7.4 Hz by
using the equation reported by Gu¨nther et al.19 This is
somewhat higher than the measured value (5.6 Hz);
however, the applied equation does not consider the effect
of the electronegative substituent (namely, the N-4 atom)
on the coupling constant. Another study established20 that
such an effect reduced the coupling constant in steric
arrangements corresponding to the conformers S12d and
3
S22d , and thus the measured J C3,H15 is also in agreement
with the expected structures.
Because the value of the measured vicinal coupling
constants fitted both proposed conformers, the decision
2
between them was made on the basis of J C3,H14 coupling-
constant values. It has been established for carbohydrates
and for other compounds that, in H-C-C-O fragments,
2
the value of J C,H depends on the dihedral angle of the
hydrogen and the oxygen atoms.21 The substituent has a
negative contribution of about 2 Hz to the coupling in
synperiplanar and sc orientation, and a positive contribu-
tion of about 2 Hz in ap arrangements. By comparison of
the coupling constants in simple O-glucosides and 2′-
deoxyribonucleosides, it was proved that the nitrogen atom
The organic solutions were dried with anhydrous sodium
sulfate. TLC was carried out on Si gel plates eluting with
CHCl3-MeOH (4:1), unless indicated otherwise. Melting points
are uncorrected. The optical rotation was measured at 583 nm
(Na) on a Carl Zeiss polarimeter.

Strictosidine and Vincoside Derivatives
J ournal of Natural Products, 1999, Vol. 62, No. 11 1497
Nb-4′-Br om oben zyltr yp ta m in e (1b). To a solution of
4-bromobenzaldehyde (0.46 g, 2.5 mmol) in benzene (4.0 mL),
tryptamine (1a , 0.40 g, 2.5 mmol) was added, the reaction
mixture refluxed for 4 h, and the solvent evaporated. The
residue was treated with absolute (Et)2O and, after filtration,
gave Nb-4′-bromobenzylidenetryptamine (1, HY ) 4-bromoben-
zylidene) (0.76 g, 90.8%, Rf 0.82, mp 118-120 °C). The crude
product (0.31 g, 1.0 mmol) was dissolved in CH3OH (4.0 mL),
and sodium tetrahydridoborate (0.06 g, 1,5 mmol) was added
in portions with stirring at room temperature, then stirred
for further 30 min, and finally refluxed for 2 h. After evapora-
tion of the solvent, the residue was taken up in H2O (3.0 mL)
and extracted with CHCl3 (3 × 5 mL). The combined CHCl3
phase was dried and the solvent evaporated. The crude Nb-
4′-bromobenzyltryptamine (1b , 0.28 g, 90%, mp 78-80 °C)
was used directly. For analysis it was dissolved in 5 M
ethanolic HCl (0.05 mL), the hydrochloric acid salt precipitated
by adding absolute (Et)2O (2.0 mL), and the precipitate was
filtered and then washed with the same solvent: mp 227-
230 °C (EtOH-hexane); anal. C 55.94%, H 4.91%, N 7.39%,
Br 22.12%, calcd for C17H18BrClN, C 55.83%, H 4.96%, N
7.66%, Br 21.85%.
ously.8 The combined yield of the two products, 3a and 5a , is
0.66 g (63%). Spectroscopic data of vincosamide (4a ): 1H NMR
3
(CD3OD, 250 MHz) δ 7.61 (1H, d, H-17), 7.58 (1H, dd, J 9,10
)
)
)
)
)
4
3
4
7.6, J 9,11 ) 1.2 Hz, H-9), 7.46 (1H, dd, J 11,12 ) 7.9, J 10,12
1.2 Hz, 12-H), 7.24 (1H, ddd, 3J 11,12 ) 7.9, 3J 10,11 ) 7.1, 4J 9,11
1.2 Hz, H-11), 7.15 (1H, ddd, 3J 9,10 ) 7.6, 3J 10,11 ) 7.1, 4J 10,12
3
3
3
1.2 Hz, H-10), 5.71 (1H, dt, J 18Z,19 ) 17.1, J 18E,19 ) J 19,20
3
10.0 Hz, H-19), 5.67 (1H, d, J 20,21 ) 1.6 Hz, H-21), 5.45 (1H,
3
2
dd, J 18Z,19 ) 17.1, J 18E,18Z ) 2.1 Hz, H-18Z), 5.35 (1H, dd,
3J 18E,19 ) 10.0, J 18E,18Z ) 2.1 Hz, H-18E), 5.23 (1H, dd, J 3,14S
2
3
3
) 11.9, J 3,14R ) 3.8 Hz, H-3), 5.09 (1H, m, H-5R), 3.20-2.85
2
(5H, m, H-5â, H-6R, H-6â, H-15, H-20), 2.63 (1H, dt, J 14R,14S
3
3
) 13.2, J 3,14R ) 3.8, J 14R,15 ) 3.8, H-14proR), 1.62 (1H, td,
3J 14S,15 ) J 14R,14S ) 13.2, J 3,14S ) 11.9, H-14proS); 13C NMR
spectral data, the same as those reported by Heckendorf et
al.24
2
3
O′,O′,O′,O′-Tet r a a cet yl-4-(4′′-b r om ob en zyl)st r ict osi-
d in e (3c) fr om 3a . To a solution of strictosidine hydrochloride
(3a ‚HCl, 0.27 g, 0.5 mmol) in MeCN (3.0 mL) 4-bromobenzyl
chloride (0.1 g, 0.5 mmol) and Dowex-1 ion-exchange resin in
the hydroxy ion form (0.5 g) was added and stirred at room
temperature for 2 h. Then the resin was filtered and washed
with acetonitrile (5 mL), the combined filtrate was dried, and
the solvent was evaporated. The 4-(4′-bromobenzyl)strictosi-
dine (3, R ) H, Y ) 4′-bromobenzyl) was obtained as a pale
yellow solid (0.2 g, single spot, Rf 0.54). It was immediately
used for the next reaction.
Secologa n in (2a ). Secologanin (2a ) was isolated from
Lonicera xylosteum L. according to a method elaborated in our
Institute23 [Rf 0.29; CHCl3-MeOH (4:1)]. 1H NMR (acetone-
3
d6, 200 MHz) δ 9.71 (1H, dd, J 6a,7 ) 1.8, 3J 6b,7 ) 1.2 Hz, H-7),
4
7.47 (1H, d, J 3,5 ) 1.8 Hz, H-3), 5.61 (1H, H-8), 5.46 (1H, d,
3J 1,9 ) 3.9 Hz, H-1), 5.32-5.16 (2H, m, H2-10), 4.70 (1H, H-1′),
A mixture of absolute pyridine (1.5 mL), (Ac)2O (0.6 mL,
6.3 mmol) and 4-(4′-bromobenzyl)strictosidine (3, R ) H, Y )
4′-bromobenzyl, 0.17 g, 0.25 mmol) was stirred at room
temperature for 2 h. The reaction mixture was poured onto
ice (10 g), extracted with CHCl3 (3 × 10 mL), and the combined
organic layer was washed with molar aqueous HCl (10 mL),
5% aqueous Na2CO3 solution (10 mL), H2O (2 × 10 mL), dried,
and the solvent evaporated. The O′,O′,O′,O′-tetraacetyl(4′′-
bromobenzyl)strictosidine (3c) was obtained as a pale yellow
solid (0.19 g, 51% calculated from 3a , Rf 0.84); anal. C 57.69%,
H 5.31%, N 3.12%, Br 9,13%, calcd for C42H47N2O13Br, C
58.11%, H 5.46%, N 3.23%, Br 9.21%; 1H NMR (C6D6, 400
MHz) δ 7.98 (1H, br s, H-1), 7.65 (1H, m, H-9), 7.51 (2H, d,
3
4.50, 4.34, 4.27 (each 1H, d, J CH,OH ) 5-6 Hz, 2′,3′,4′-OH),
3.92-3.60 (3H, H2-6′, 6′-OH), 3.64 (3H, s, OCH3), 3.50-3.18
2
3
(5H, m, H-5,2′,3′,4′,5′), 2.83 (1H, ddd, J 6a,6b ) 17.5, J 5,6a
)
3
6.1, J 6a,7 ) 1.8 Hz, H-6a), 2.75 (1H, m, H-9), 2.42 (1H, ddd,
2J 6a,6b ) 17.5, J 5,6b ) 7.4, J 6b,7 ) 1.2 Hz, H-6b); 13C NMR
(acetone-d6, 50 MHz) δ 202.0 (C-7), 168.2 (C-11), 153.6 (C-3),
135.4 (C-8), 120.9 (C-10), 110.3 (C-4), 100.4 (C-1′), 97.5 (C-1),
78.7, 78.5 (C-3′,5′), 75.1 (C-2′), 72.2 (C-4′), 63.5 (C-6′), 52.0
(OCH3), 45.7 (C-9), 45.1 (C-6), 27.3 (C-5).
3
3
O,O,O,O-Tetr a a cetylsecologa n in (2b). Secologanin 2a
(7.5 g, 0.020 mol) was dissolved in a mixture of anhydrous
pyridine (30 mL, 0.38 mol) and (Ac)2O (15 mL, 0.15 mol),
stirred at room temperature for 2 h, poured on to ice (150 g),
and extracted with CHCl3 (3 × 90 mL). The combined CHCl3
layer was washed with 2 M aqueous HCl (2 × 60 mL), 5%
aqueous NaHCO3 (60 mL), and H2O (2 × 60 mL) and dried.
Evaporation of the solvent gave O,O,O,O-tetraacetylsecologa-
4
3J 2′′3′′ ) 3J 5′′6′′ ) 8.5 Hz, H-3′′,5′′), 7.44 (1H, d, J 15,17 ) 1.9, Hz,
3
H-17), 7.3-7.2 (3H, m, H-10, H-11, H-12), 7.20 (2H, d, J 2′′3′′
) 3J 5′′6′′ ) 8.5 Hz, H-2′′,6′′), 5.55 (1H, ddd, 3J 18Z,19 ) 17.2, 3J 18E,19
) 10.4, 3J 19,20 ) 9.4 Hz, H-19), 5.5-5.3 (3H, m, H-2′,3′,4′), 5.36
3
3
(1H, d, J 20,21 ) 3.1 Hz, H-21), 5.01 (1H, dd, J 18E,19 ) 10.4,
1
nin 2b (9.2 g, 84.5%, Rf 0.69); H NMR (CDCl3, 200 MHz) δ
2J 18E,18Z ) 1.6 Hz, H-18E), 4.89 (1H, dd, 3J 18Z,19 ) 17.2, 2J 18E,18Z
3
3
3
9.71 (1H, dd, J 6a,7 ) 1.6, J 6b,7 ) 0.7 Hz, H-7), 9.42 (1H, d,
) 1.6 Hz, H-18Z), 4.78 (1H, d, J 1′,2′ ) 8.0 Hz, H-1′), 4.36 (1H,
4J 3,5 ) 1.9 Hz, H-3), 5.50 (1H, dt, J 8,10E ) 17.9, J 8,9 ) J 8,10Z
dd, J 6′a,6′b ) 12.5, J 5′,6′a ) 3.5 Hz, H-6′a), 3.99 (1H, dd, J 3,14R
3 2
3
3
3
2
3
3
3
) 8.9 Hz, H-8), 5.28 (1H, d, J 1,9 ) 2.9 Hz, H-1), 5.23-4.97
) 8.7, J 3,14S ) 4.2 Hz, H-3), 3.94 (1H, dd, J 6′a,6′b ) 12.5 Hz,
3
(5H, m, H-10E, H-10Z, H-2′, H-3′, H-4′), 4.88 (1H, d, J 1′,2′
)
H-6′b), 3.67 (1H, d, 2J NCHa,NCHb ) 13.2 Hz, Ha-benzyl-CH2), 3.55
2
3
2
7.9 Hz, H-1′), 4.29 (1H, dd, J 6′a,6′b ) 12.4, J 5′,6′a ) 4.4 Hz,
(1H, d, J NCHa,NCHb ) 13.2 Hz, Hb-benzyl-CH2), 3.30 (3H, s,
2
3
H-6′a), 4.15 (1H, dd, J 6′a,6′b ) 12.4, J 5′6′b ) 2.3 Hz, H-6′b),
3.77-3.71 (1H, m, H-5′), 3.68 (3H, s, OCH3), 3.28 (1H, dtd,
OCH3), 3.23 (1H, tdd, 3J 15,20 ) 3J 14R,15 ) 5.8; 3J 14S,15 ) 4.2; 4J 15,17
2
) 1.9 Hz, H-15), 3.12 (1H, m, Hz, H-5′), 2.97 (1H, ddd, J 5R,5â
3J 5,6b ) 7.7, J 5,6a ) J 5,9 ) 5.7, J 3,5 ) 1.9 Hz, H-5), 2.92 (1H,
) 13.3, J 5â,6R ) 10.6, J 5â,6â ) 4.5 Hz, H-5â), 2.81 (1H, ddd,
3 3
3
3
4
3
3
2
3
3
ddd, J 6a,6b ) 17.8, J 5,6a ) 5.7, J 6a,7 ) 1.6 Hz, H-6a), 2.85-
3J 19,20 ) 9.4; J 15,20 ) 5.8, J 20,21 ) 3.1 Hz, H-20), 2.80 (1H,
2 3 3
2
3
2.76 (1H, m, H-9), 2.39 (1H, ddd, J 6a,6b ) 17.8, J 5,6b ) 7.7,
3J 6b,7 ) 0.7 Hz, H-6b), 2.11, 2.03, 2.01, 1.91 (each 3H, s, CH3-
CO). 13C NMR (CDCl3, 50 MHz) δ 205.9 (C-7), 170.6, 170.2,
169.4, 168.9 (4 CH3CO of acetyl), 166.8 (C-11), 151.3 (C-3),
132.3 (C-8), 121.1 (C-10), 109.6 (C-4), 95.8 (C-1, C-1′); 72.3 (C-
3′), 72.4 (C-2′), 70.6 (C-4′), 68.1 (C-5′), 61.6 (C-6′), 51.3 (CH3O),
43.7 (C-9), 43.3 (C-6), 25.1(C-5), 20.7, 20.6, 20.1 (each CH3-
CO).
Str ictosid in e (3a ) a n d Vin cosa m id e (4a ). Tryptamine
base (1a , 0.16 g, 0.10 mmol) and tryptaminium chloride (1a ‚
HCl, 0.20 mmol) were dissolved in a mixture of H2O (10 mL)
and glacial HOAc (0.50 mL), secologanin (2a , 0.76 g, 0.20
mmol) was added, and the solution stirred in a N2 atmosphere
at 100 °C for 6 h. From the cooled reaction mixture the
precipitated vincosamide (4a ) was filtered, and the mother
liquor extracted with EtOAc (3 × 30 mL). The combined
organic layer was dried, and the solvent evaporated. The
residue (5a ) was crystallized from acetone (0.27 g, 27%).
Isolation of strictosidine (3a , 0.39 g, 36%) from the mother
liquor as well as its spectroscopic data were described previ-
ddd, J 6R,6â ) 15.5, J 5â,6R ) 10.6, J 5R,6R ) 5.3 Hz, H-6R), 2.71
2 3 3
(1H, ddd, J 5R,5â ) 13.3, J 5R,6R ) 5.3, J 5R,6â ) 1.4 Hz, H-5R),
2.29 (1H, ddd, 2J 6R,6â ) 15.5, 3J 5â,6â ) 4.5, 3J 5R,6â ) 1.4 Hz, H-6â),
2.27 (1H, dt, 2J 14R,14S ) 14.3, 3J 3,14S ) 3J 14S,15 ) 4.2 Hz, H-14S),
2
3
3
1.83 (1H, ddd, J 14R,14S ) 14.3, J 3,14R ) 8.7, J 14R,15 ) 5.8 Hz,
H-14R), 1.80, 1.76, 1.69, 1.66 (each 3H, s, CH3CO). The
assignments were supported by a COSY spectrum. Some
coupling constants were obtained from selective TOCSY
measurements. 13C NMR (CDCl3, 100 MHz) δ 170.7, 170.3,
169.4, 169.1 (each CH3CO), 167.3 (C-22), 150.7 (C-17), 139.1
(C-1′′), 135.9a (C-2), 135.4a (C-13), 133.2 (C-19), 131.3c (C-
3′′,5′′), 130.9c (C-2′′,6′′), 127.2 (C-8), 121.3 (C-11), 120.5 (C-
18), 120.7 (C-4′′), 119.1 (C-10), 118.0 (C-9), 111.7 (C-16), 110.9
(C-12), 107.7 (C-7), 96.4 (C-21), 95.9 (C-1′), 72.3b (C-3′), 72.2b
(C-5′), 70.7 (C-2′), 68.2 (C-4′), 61.6 (C-6′), 58.6 (C-3), 57.0 (CH2-
benzyl), 51.3 (CH3O), 44.7 (C-20), 42.2 (C-5), 34.4 (C-14), 28.8
(C-15), 20.8, 20.7, 20.6, 20.2 (each CH3CO), 16.6 (C-6); a, b, c,
revised assignment is also possible. 13C-1H coupling constants
in Hertz (the magnitude and the sign of the coupling constants
were determined from the displacement of the signals in the

1498 J ournal of Natural Products, 1999, Vol. 62, No. 11
Patthy-Luka´ts et al.
3
3
HETLOCK spectrum15): J C15,H3 ) +3.2, J C3,H15 ) +5.5,
CO); 17.1 (C-6); a, b, c, revised assignment is also possible.
NOESY cross-peaks (s, strong; m, medium; w, weak; v, very
weak): H-1, H-3 w, H-12 w, H-15 w; H-3, H-14proR w,
H-14proS v, H-15 w, H-18Z w, H-20 m, H-2′ m, Hb-benzyl-
CH2 m; H-5R, H-5â s, H-6R v, H-14proS v, H-15 v; H-5â, H-5R
s, H-6â v, Ha-benzyl-CH2 w; H-6R, H-5R v, H-6â s, H-9 w; H-6â,
H-5â v, H-6R s, H-9 v, Ha-benzyl-CH2 v, Hb-benzyl-CH2 v; H-9,
H-6R w, H-6â v, H-10 s; H-10, H-9 s; H-11, H-12 s; H-12, H-1
w, H-11 s; H-14proR, H-3 v, H-14proS s, H-15 v, H-19 w;
H-14proS, H-3 v, H-5R v, H-14proR s, H-15 w; H-15, H-3 w,
H-5R v, H-14proR v, H-14proS w, H-20 s, H-2′′ m; H-18E,
H-18Z s, H-19 s; H-18Z, H-18E s, H-19 w, H-20 s; H-19,
H-14proR w, H-18E s, H-18Z w, H-20 v; H-20, H-3 m, H-15 s,
H-18Z s, H-19 v, H-21 s, H-2′′ w; H-21, H-20 s, H-1′ m; Ha-
benzyl-CH2, H-5â w, H-6â w, Hb-benzyl-CH2 s, 2′′-H m; Hb-
benzyl-CH2, H-3 m, H-6â v, Ha-benzyl-CH2 s, H-2′′ m.
3J C20,H18Z ) +6.3, J C20,H18E ) +11.6, J C20,H21 ) +0.3, J C15,H19
3
2
3
2
2
2
) +5.1, J C20,H15 ) -7.1, J C15,H20 ) -3.5, J C15,H14S ) -5.0,
2J C3,H14S ) -2.6, J C3,H14R ) -6.0, J C14,H3 ) -4.0, J C14,H15
)
2
2
2
-5.3. The cross-peak intensities of the NOESY spectrum were
obtained from volume integration by the XWINNMR program.
The intensity of the NOE interaction corresponding to 3.3 Å
distance of two hydrogens were calculated by the two inde-
pendent spin approximation from the known 2.5 Å distance
of H-1′ and H-5′ hydrogens and from the measured cross-peak
intensity of this interaction. NOEs larger and smaller than
the calculated value are denoted as strong (s) and weak (w),
respectively. List of NOESY cross-peaks: H-1, H-3 s, H-12 w,
H-14proS w, H-15 s; H-3, H-14proS s, H-14proR w, H-15 s,
H-20 w, Ha-benzyl-CH2 s, Hb-benzyl-CH2 w; H-5R, H-5â s,
H-6â w, Hb-benzyl-CH2 s; H-5â, H-5R s, H-6â s, H-14proR s;
H-6R, H-6â s, H-9 w, Ha-benzyl-CH2 w, Hb-benzyl-CH2 s; H-6â,
H-5â s, H-6R s, H-9 w; H-9, H-6R w, H-6â w, H-10 s; H-14proR,
H-3 w, H-5â s, H-14proS s, H-15 w, H-20 w; H-14proS, H-3 s,
H-14proR s, H-15 w; H-15, H-1 s, H-3 s, H-14proR w, H-14proS
w, H-20 s, H-2′′ w, Ha-benzyl-CH2 w; H-18E, H-18Z s, H-19 s;
H-18Z, H-18E s, H-20 s; H-19, H-18E s, H-20 w; H-20, H-3 w,
H-14proR w, H-15 s, H-18Z s, H-19 w, H-21 s; H-21, H-20 s,
H-18Z w; Ha-benzyl-CH2, H-3 s, H-6R w, H-15 w, Hb-benzyl-
CH2 s, H-2′′ 2.6 s; Hb-benzyl-CH2, H-5R 2.3 s, H-6R 2.3 s, Ha-
benzyl-CH2 s, H-2′′ s.
O′,O′,O′,O′-Tetr a a cetyl-18,19-d ih yd r ovin cosa m id e (4b)
P r ep a r ed fr om 3d . O′,O′,O′,O′-Tetraacetyl-4-(4′′-bromoben-
zyl)vincoside (3d , 0.43 g, 0.5 mmol) was dissolved in absolute
MeOH (10.0 mL) and hydrogenated in the presence of 10%
Pd on charcoal at room temperature for 30 min, then the
catalyst was filtered, and the solution stirred for 2 h. After
evaporation of the solvent O′,O′,O′,O′-tetraacetyl-18,19-dihy-
drovincosamide (4b) was obtained as a pale yellow amorphous
solid (0.28 g, 84%, Rf 0.84); anal. C 60.61%, H 5.85%, N 4.02%,
calcd for C34H40N2O12, C 61.05%, H 6.03%, N 4.19%; 1H NMR
3
(CDCl3, 400 MHz) δ 8.00 (1H, br s, H-1), 7.51 (1H, dd, J 9,10
)
O′,O′,O′,O′-Tet r a a cet yl-4-(4′′-b r om ob en zyl)vin cosid e
(3d ). Nb-4′-bromobenzyltryptaminium chloride (1b‚HCl, 0.25
g, 0.06 mmol) was dissolved in H2O (3.0 mL) and, after the
addition of 5% aqueous Na2CO3 solution (1 mL), was extracted
with CHCl3 (3 × 3.0 mL). The combined CHCl3 solution was
washed with H2O (2 × 3 mL), dried, and the solvent evapo-
rated. The residue was taken up in C6H6 (5.0 mL), O,O,O,O-
tetraacetylsecologanin (2b, 0.34 g, 0.6 mmol) was added, and
the reaction mixture refluxed for 3 h. The solvent was
evaporated, and the residue crystallized from MeOH-H2O
(1:1, 1.5 mL). O′,O′,O′,O′-Tetraacetyl-4-(4′′-bromobenzyl)vin-
coside (3d ) was obtained as colorless crystals (0.48 g, 91%, Rf
4
4
7.5, J 9,11 ) 1.2 Hz, H-9), 7.42 (1H, d, J 15,17 ) 2.5 Hz, H-17),
3
4
7.34 (1H, dd, J 11,12 ) 8.0, J 10,12 ) 1.2 Hz, H-12), 7.19 (1H,
ddd, 3J 11,12 ) 8.0, 3J 10,11 ) 7.5, 4J 9,11 ) 1.2, Hz, H-11), 7.12 (1H,
3J 10,11 ) td, 7.5, J 9,10 ) 7.5, J 10,12 ) 1.2 Hz, H-10), 5.40 (1H,
3
4
3
3
3
d, J 20,21 ) 1.9 Hz, H-21), 5.26 (1H, t, J 2′,3′ ) J 3′,4′ ) 9.8 Hz,
3
3
H-3′), 5.14 (1H, m, H-5R), 5.10 (1H, t, J 3′,4′ ) J 4′,5′ ) 9.8 Hz,
H-4′), 5.02 (1H, dd, 3J 1′,2′ ) 8.0, 3J 2′,3′ ) 9.8 Hz, H-2′), 4.93 (1H,
d, 3J 1′,2′ ) 8.0 Hz, H-1′), 4.83 (1H, m H-3), 4.34 (1H, dd, 3J 6′a,6′b
3
3
) 12.6, J 5′,6′a ) 3.9 Hz; H-6′a), 4.15 (1H, dd, J 6′a,6′b ) 12.6,
3J 5′,6′b ) 2.0 Hz, H-6′b), 3.78 (1H, ddd, J 4′,5′ ) 9,8, J 5′,6′a
)
3
3
3.9, 3J 5′,6′b ) 2.0 Hz, H-5′), 2.96 (1H, dddd, 3J 14S,15 ) 13.0, 3J 15,20
) 6.2, 3J 14R,15 ) 3.5, 4J 15,17 ) 2.5 Hz, H-15), 2.88 (1H, m, H-5â),
25
0.86, mp 159-160 °C, [R]D -63° (c 0.1, MeOH); IR (KBr),
2
3
3
cm-1: 1715, 1680 (νCdO); anal. C 57.53%, H 5.35%, N 3.17%,
Br 9.15%, calcd for C42H47N2O13Br, C 58.11%, H 5.46% N
3.23%, Br 9.21%; 1H NMR (CDCl3, 400 MHz) δ 8.10 (1H, br s,
2.80 (2H, H2-6), 2.23 (1H, dt, J 14R,14S ) 12.7, J 3,14R ) J 14R,15
) 3.6 Hz, H-14proR), 2.11, 2.04, 2.02, 1,98 (each 3H, s, CH3-
3
3
3
CO),1.90 (1H, dddd, J 19b,20 ) 9.8, J 15,20 ) 6.2, J 19a,20 ) 5.0,
3J 20,21 ) 1.9 Hz, H-20), 1.66 (1H, q, J 14R,14S ) 3J 3,14S ) 3J 14S,15
2
3
4
H-1), 7.51 (1H, dd, J 9,10 ) 8.3, J 9,11 ) 1.4 Hz, H-9), 7.49 (2H,
2
3
d, J 2′′,3′′ Hz ) 3J 5′′,6′′ ) 8.4 Hz, H-3′′,5′′), 7.32 (1H, dd, J 11,12
)
3
3
) 12.7 Hz, H-14proS), 1.36 (1H, dqd, J 19a,19b ) 14.3, J 18,19
)
3
2
7.9, 4J 10,12 ) 1.2 Hz, H-12), 7.31 (1H, d, 4J 15,17 ) 1.4 Hz, H-17),
7.5, J 19a,20 ) 5.0 Hz, H-19a), 1.13 (1H, ddq, J 19a,19b ) 14.3;
3J 19b,20 ) 9.8; 3J 18,19 ) 7.5 Hz, H-19b), 0.95 (3H, t, J 18,19 ) 7.5
3
3
3
7.24 (2H, d, J 2′′,3′′ Hz ) J 5′′,6′′ ) 8.4 Hz, H-2′′,6′′), 7.14 (1H,
Hz, H-18). Further 1H coupling constants determined in
ddd, 3J 11,12 ) 7.9, 3J 10,11 ) 7.1, 4J 9,11 ) 1.4 Hz, H-11), 7.10 (1H,
5
2
3
3
3
3
4
C6D6: J 3,6R ) 2.3, J 5R,5â ) 12.3, J 5R,6R ) 4.8, J 5R,6â ) 1.3,
3J 5â,6R ) 12,3, 3J 5â,6â ) 3.3, 2J 6R,6â ) 14.5 Hz; 13C NMR (CDCl3,
100 MHz) δ 170,6, 169.9, 169.8, 169.5 (each CH3CO), 163.3 (s,
C-22), 146.7 (d, C-17), 136.4 (s, C-13), 132.9 (s, C-2), 126.7 (s,
C-8), 122.1 (d, C-11), 119.7 (d, C-10), 118.3 (d, C-9), 111.0 (d,
C-12), 109.4 (s, C-16), 108.6 (s, C-7), 95.9 (d, C-21), 95.0 (d,
C-1′), 72.3 (d, C-3′), 72.1 (d, C-5′), 70.6 (d, C-2′), 68.3 (d, C-4′),
61.8 (t, C-6′), 53.2 (d, C-3), 39.5 (t, (C-5), 38.0 (d, C-20), 31.1
(t, C-14), 27.4 (d, C-15), 21.0 (t, C-6), 20.7-20.5 (CH3CO), 17.6
(t, C-19), 11.9 (q, C-18); NOESY cross-peaks H-3, H-14proR
w, H-15 w; H-5R, H-5â s, H-6R w; H-5â, H-5R s, H-6â w; H-6R,
H-5R w, H-6â s; H-6â, H-5â w, H-6Rs; H-14proR, H-3 w,
H-14proS s; H-14proS, H-14proR s; H-15, H-3 w, H-20 m; H3-
18, H-21 s, H2-19 m; H2-19, H3-18 m, H-20 m; H-20, H-15 m,
H2-19 m, H-21 m; H-21, H3-18 s, H-20 m, H-1′ m.
O′,O′,O′,O′-Tetr a a cetyl-18,19-d ih yd r ovin cosa m id e (4b)
P r ep a r ed fr om Vin cosa m id e (4a ). In a mixture of absolute
pyridine (2.0 mL) and (Ac)2O (0.8 mL, 8.0 mmol) vincosamide
(4a , 0.25 g, 0.4 mmol) was stirred at room temperature for 2
h, the reaction mixture was poured on to ice (5.0 g), and
extracted with EtOAc (3 × 10 mL). The organic layer was
washed with 5% aqueous Na2CO3 solution (2 × 10 mL) and
H2O (10 mL), dried with anhydrous Na2SO4, and the solvent
evaporated. The O′,O′,O′,O′-tetraacetylvincosamide (4c ) 4,
R ) acetyl, X ) vinyl) was obtained as a pale yellow powder
(0.26 g, single spot, Rf 0.86) and was used immediately.
O′,O′,O′,O′-Tetraacetylvincosamide (4c) was dissolved in
absolute methanol (3.0 mL) and hydrogenated in the presence
ddd, J 9,10 ) 8.3, J 10,11 ) 7.1, J 9,11 ) 1.4 Hz, H-10), 5.53 (1H,
ddd, 3J 18Z,19 ) 17.2, 3J 18E,19 ) 10.2, 3J 19,20 ) 9.5 Hz, H-19), 5.30-
3
2
5.08 (3H, m, H-2′,3′,4′), 5.18 (1H, dd, J 18E,19 ) 10.2, J 18E,18Z
3
) 1.8 Hz, H-18E), 5.16 (1H, d, J 20,21 ) 4.0 Hz, H-21), 4.88
3
3
(1H, d, J 1′,2′ ) 8.1 Hz, H-1′), 4.86 (1H, dd, J 18Z,19 ) 17.2,
2J 18E,18Z ) 1.8 Hz, H-18Z), 4.35 (1H, dd, J 6′a,6′b ) 12.4, J 5′,6′a
2
3
2
3
) 4.1 Hz, H-6′a), 4.24 (1H, dd, J 6′a,6′b ) 12.4, J 5′,6′b ) 2.3 Hz,
2
H-6′b), 3.76 (1H, m, H-5′), 3.76 (1H, d, J NCHa,NCHb ) 13.1 Hz,
2
Ha-benzyl-CH2), 3.61 (3H, s, OCH3), 3.59 (1H, J NCHa,NCHb
)
)
3
3
13.1 Hz, Hb-benzyl-CH2), 3.48 (1H, dd, J 3,14S ) 9.4, J 3,14R
5.5 Hz, H-3), 3.41 (1H, ddd, 2J 5R,5â ) 13.7, 3J 5R,6â ) 11.8, 3J 5R,6R
2
3
) 4.8 Hz, H-5R), 3.16 (1H, ddd, J 5R,5â ) 13.7, J 5â,6â ) 5.7,
3J 5â,6R ) 1.0 Hz, H-5â), 3.06 (1H, dtd, J 14R,15 ) 9.5, J 14S,15
)
)
3
3
3J 15,20 ) 5.3, J 15,17 ) 1.4 Hz, H-15), 2.96 (1H, ddd, J 6R,6â
4
2
16.2, 3J 5R,6â ) 11.8, 3J 5â,6â ) 5.7 Hz, H-6â), 2.57 (1H, ddd, 2J 6R,6â
3
3
) 16.2, J 5R,6R, ) 4.8, J 5â,6R ) 1.0 Hz, H-6R), 2.30 (1H, ddd,
2J 14R14S ) 14.3, 3J 14R,15 ) 9.5 Hz, 3J 3,14R ) 5.5, H-14proR), 2.12,
3
2.05, 2.04, 1.96 (each 3H, s, CH3CO), 2.00 (1H, ddd, J 19,20
)
9.5, 3J 15,20 ) 5.3, 3J 20,21 ) 4.0 Hz, H-20), 1.52 (1H, ddd, 2J 14R14S
) 14.3, J 3,14S ) 9.4, J 14S,15 ) 5.3 Hz, H-14proS); 13C NMR
(CDCl3, 100 MHz) δ 170.8, 170.2, 169.4, 169.1 (each CH3CO),
167.4 (C-22), 150.7 (C-17), 138.9 (C-1′′), 135.7 (C-13), 134.8 (C-
2), 133.7 (C-19), 131.4c (C-3′′,5′′), 131.3c (C-2′′,6′′), 127.4 (C-
8), 121.3 (C-11), 120.8 (C-4′′), 119.6 (C-18), 119.2 (C-10), 118.0
(C-9), 111.7 (C-16), 110.8 (C-12), 106.8 (C-7), 96.2 (C-21), 95.8
(C-1′), 72.5b (C-3′), 72.1b (C-5′), 70.7 (C-2′), 68.2 (C-4′), 61.7
(C-6′), 56.4 (CH2), 51.3a (OCH3), 51.2a (C-3), 44.3 (C-5), 42.4
(C-20), 33.8 (C-14), 26.4 (C-15), 20.8, 20.6, 20.5, 20.2 (each CH3-
3
3

Strictosidine and Vincoside Derivatives
J ournal of Natural Products, 1999, Vol. 62, No. 11 1499
of 10% Pd on charcoal at room temperature for 20 min. After
filtration of the catalyst and evaporation of the solvent,
O′,O′,O′,O′-tetraacetyl-18,19-dihydrovincosamide (4b) was ob-
tained as a pale yellow amorphous powder (0.16 g, 47%
calculated from 4a , single spot, Rf 0.84). The spectroscopic data
established the identity to O′,O′,O′,O′-tetraacetyl-18,19-dihy-
drovincosamide (4b) prepared from O′,O′,O′,O′-tetraacetyl-4-
(4′′-bromobenzyl)vincoside (3d ) (see above).
(C-13), 132.8 (C-2), 127.5s (C-8), 122.2d (C-11), 119.8d (C-10),
118.0d (C-9), 111.3d (C-12), 110.7s (C-16), 108.5s (C-7), 95.1d
(C-21), 93.8 (C-1′), 72.1, 72.0 (C-3′, C-5′), 68.3 (C-4′), 61.7 (C-
6′), 70.0 (C-2′), 53.5d (C-3), 43.7t (C-5), 37.9d (C-20), 25.7t (C-
14), 24.8d (C-15), 21.0t (C-6), 20.7, 20.6, 20.5, 19.2 (CH3CO of
acetyl), 17.6t (C-19), 12.2q (C-18); NOESY cross-peaks (in
C6D6), H-3, H-5R s, H-5â w, H-14proR m, H-14proS m; H-5R,
H-3 s, H-5â s, H-6R w; H-5â, H-3 w, H-5R s; H-6R, H-6â s, H-9
m; H-6â, H-6R s, H-9 w; H-9, H-6R m, H-6â w, H-10 m, 2′-OAc
m; H-10, H-9 m, H-11 m; H-11, H-10 m, H-12 m, 2′-OAc v;
H-12, H-11 m, H-14proS w; H-14proS, H-3 m, H-12 w,
H-14proR m; H-14proR, H-3 m, H-14proS m, H-15 w; H-15,
H-14proR w, H-20 s, 2′-OAc w; H-17, H-1′ w; H3-18, H-19a m,
H-19b w, H-20 m, H-21 s; H-19a, H3-18 m, H-19b s; H-19b,
H3-18 m, H-19a m, H-20w, H-21w; H-20, H-15 s, H3-18 m,
H-19b w, H-21 s; H-21, H3-18 m, H-19b w, H-20 s, H-1′ m.
O′,O′,O′,O′-Tetr aacetyl-18,19-dih ydr ostr ictosam ide (5b)
fr om 3c. O′,O′,O′,O′-Tetraacetyl-4-(4′′-bromobenzyl)strictosi-
dine (3c, 0.17 g, 0.2 mmol) was dissolved in absolute MeOH
and hydrogenated in the presence of 10% Pd on charcoal (0.05
g) at room temperature for 30 min. Triethylamine (0.07 mL,
0.5 mmol) was added and the reaction mixture refluxed for 1
h. After evaporation of the solvent, the residue was dissolved
in EtOAc (10 mL) and extracted with H2O (2 × 5 mL). The
organic phase was dried and the solvent evaporated. O′,O′,O′,O′-
Tetraacetyl-18,19-dihydrostrictosamide (5b) was obtained as
a pale yellow amorphous solid (0.11 g, 84%, single spot, Rf
0.84). According to its spectroscopic data, the sample was
identical to 5b obtained from 5a .
Str ictosa m id e (5a ). Strictosidine hydrochloride8 (3a ‚HCl,
0.27 g, 0.5 mmol) was stirred in 5% aqueous Na2CO3 solution
at 70 °C for 2 h. The cooled reaction mixture was extracted
with EtOAc (3 × 10 mL), the combined organic layer was
washed with H2O (2 × 5 mL) and dried, and the solvent was
evaporated. Strictosamide (5a ) was obtained as a pale yellow
solid (0.19 g, 80%, single spot, Rf 0.30); 1H NMR (CD3OD, 250
MHz) δ 7.55 (1H, dd, 3J 11,12 ) 7.3, 4J 10,12 ) 1.2 Hz, H-12), 7.54
4
3
4
(1H, d, J 15,17 ) 2.4 Hz, H-17), 7.49 (1H, dd, J 9,10 ) 8.0, J 9,11
) 1.2 Hz, H-9), 7.24 (1H, td, J 10,11 ) 3J 11,12 ) 7.3, J 9,11 ) 1.2
3
4
Hz, H-11), 7.15 (1H, ddd, 3J 9,10 ) 8.0, 3J 10,11 ) 7.3, 4J 10,12 ) 1.2
3
3
3
Hz, H-10), 5.82 (1H, dt J 18Z,19 ) 17.1, J 18E,19 ) J 19,20 ) 10.0
3
Hz, H-19), 5.57 (1H, d, J 20,21 ) 1.8 Hz, H-21), 5.53 (1H, dd,
3J 18Z,19 ) 17.1, 2J 18E,18Z ) 2.1 Hz, H-18Z), 5.48 (1H, dd, 3J 18E,19
2
3
) 10.0, J 18E,18Z ) 2.1 Hz, H-18E), 5.23 (1H, dd, J 3,14R ) 2.0,
3J 3,14S ) 6.1 Hz, H-3), 5.11 (1H, m, H-5â), 4,74 (1H, d, J 1′,2′
)
3
2
3
7.9 Hz, H-1′), 3.97 (1H, J 6′a,6′b ) 11.7, J 5′,6′a ) 1.7 Hz, H-6′a),
3.65 (1H, 2J 6′a,6′b ) 11.7, 3J 5′,6′b ) 5.2 Hz, H-6′b), 3.20-3.50 (4H,
m, H-2′,3′,4′,5′), 2.80-3.35 (5H, m, H-5R, H-6R, H-6â, H-15,
2
3
3
H-20), 2.63 (1H, ddd, J 14R,14S ) 14.0, J 14R,15 ) 4.3, J 3,14R
)
2.0 Hz, H-14proR), 2.20 (1H, td, 2J 14R,14S ) 3J 14S,15 ) 14.0, 3J 3,14S
) 6.1 Hz, H-14proS; 13C NMR spectral data are comparable
to those reported by Heckendorf et al.24
Ack n ow led gm en t. Financial support of this work by the
National Scientific Research Foundation is gratefully acknowl-
edged.
O′,O′,O′,O′-Tetr aacetyl-18,19-dih ydr ostr ictosam ide (5b)
fr om 5a . Strictosamide (5a , 0.14 g, 0.25 mmol) was stirred in
a mixture of absolute pyridine (1.5 mL) and (Ac)2O (0.6 mL)
at room temperature for 2 h, then poured onto ice (10 mL)
and extracted with CHCl3 (3 × 10 mL). The combined organic
layer was washed with molar aqueous HCl (10 mL), 5%
aqueous Na2CO3 solution (10 mL), H2O (2 × 10 mL) and dried.
After evaporation of the solvent O′,O′,O′,O′-tetraacetylstric-
tosamide (5c ) 5, R ) acetyl, X ) vinyl) was obtained as a
yellow solid (0.16 g, single spot, Rf 0.87). The sample was used
immediately for preparation of 5b.
Refer en ces a n d Notes
(1) Part 5 of this series: Ka´rolyha´zy, L.; Patthy-Luka´ts, AÄ .; Szabo´, L. F.
J . Phys. Org. Chem. 1998, 11, 622-631.
(2) Treimer, J . F.; Zenk, M. H. Eur. J . Biochem. 1979, 81, 225-233.
(3) Battersby, A. R.; Burnett, A. R.; Parsons, P. G. J . J . Chem. Soc. 1969,
1193-1200.
(4) Cordell, G. A. Lloydia 1974, 37, 219-298.
(5) Hutchinson, C. R.; Heckendorf, A. H.; Straugh, J . L.; Daddona, P.
E.; Cane, D. E. J . Am. Chem. Soc. 1979, 101, 3358-3369.
(6) Arbain, D.; Putra, D. P.; Sargent, M. V. Aust. J . Chem. 1993, 46, 977-
985.
(7) Tits, M.; Brandt, V.; Wauters, J .-N.; Delaude, C.; Lkabres, G.;
Angenot, L. Planta Med. 1996, 62, 73-74.
O′,O′,O′,O-Tetraacetylstrictosamide 5c (0.15 g, 0.23 mmol)
was dissolved in MeOH (10 mL), and hydrogenated in the
presence of 10% Pd on charcoal (0.10 g) at room temperature
for 30 min. After filtration of the catalyst and evaporation of
the solvent, O′,O′,O′,O′-tetraacetyl-18,19-dihydrostrictosamide
(5b) was obtained as a pale yellow amorphous solid (0.14 g,
70%, single spot, Rf 0.84); anal. C 60.72%, H 5.76%, N 3.97%,
(8) Patthy-Luka´ts, AÄ .; Ka´rolyha´zy, L.; Szabo´, L. F.; Poda´nyi, B. J . Nat.
Prod. 1997, 60, 69-75.
(9) Ohmori, O.; Kumazawa, K.; Hoshino, H.; Suzuki, T.; Morishima, Y.;
Kohno, H.; Kitajima, M.; Sakai, S.; Takayama, H.; Aimi, N. Tetra-
hedron Lett. 1998, 39, 7737-7740.
(10) In the formulas, a biogenetic numbering system was used.11 For
characterization of the stereochemical pattern of the possible isomers,
a uniform system was constructed using the letters R and S for the
configuration of the new chiral center C-3, the numbers 11, 12, etc.
for the rotation pattern around the methylene bridge, letters N and
P for the negative and positive conformation of dihydropyran and
tetrahydropyridine rings, and the letters A and E for the axial and
equatorial position of the eventual benzyl group, respectively.
(11) Le Men, J .; Taylor, W. I. Experientia 1965, 21, 508.
(12) ALCHEMY II molecular modeling system fro the IBM PC. Tripos
Associates, Inc., St. Louis, MO.
calcd for C34H40N2O12, C 61.05%, H 6.03%, N 4.19%; 1H NMR
3
(CDCl3, 400 MHz) δ 8.35 (1H, br s, H-1), 7.41 (1H, dd, J 9,10
)
4
3
4
7.9, J 9,11 ) 1.2 Hz, H-9), 7.38 (1H, dd, J 11,12 ) 8.2, J 10,12
)
4
1.2 Hz, H-12), 7.36 (1H, d, J 15,17 ) 2.6 Hz, H-17), 7.18 (1H,
ddd, 3J 11,12 ) 8.2, 3J 10,11 ) 7.1, 4J 9,11 ) 1.2 Hz, H-11), 7.09 (1H,
ddd, 3J 9,10 ) 7.9, 3J 10,11 ) 7.1, 4J 10,12 ) 1.2 Hz, H-10), 5.38 (1H,
3
d, J 20,21 ) 1.8 Hz, H-21), 5.12 (1H, m, H-3′), 5.02 (1H, Hz,
ddd, J 5R,5â ) 13.0, J 5â,6â ) 6.0, J 5â,6R ) 1.0 Hz, H-5â), 5.01
2
3
3
(13) Lentz, P. J ., J r.; Rossmann, M. G. Chem Commun. 1969, 1269.
(14) Bohlmann, F.; Schumann, D. Tetrahedron Lett. 1965, 2435-2440.
(15) Bax, A. J . Magn. Reson. 1984, 57, 314-318
3
3
5
5
(1H, dddd, J 3,14S ) 5.5, J 3,14R ) 2.8, J 3,6â ) 2.5, J 3,6R ) 1.0
Hz, H-3), 4.98 (1H, m, H-4′), 4.75 (2H, m, H-1′, H-2′), 4.27 (1H,
dd, 3J 6′a,6′b ) 12.6, 3J 5′,6′a ) 3.9 Hz, H-6′a), 4.10 (1H, dd, 3J 6′a,6′b
(16) Takayama, H.; Ohmori, O.; Subhadhirasakul, S.; Kitajima, M.; Aimi,
N. Chem. Pharm. Bull. 1997, 45, 1231-1233.
3
(17) Uhrin, D.; Batta, G.; Hruby, V. J .; Barlow, P. N.; Ko¨ve´r, K. E. J . Magn.
Reson. 1998, 130, 155-161.
) 12.6, J 5′,6′b ) 2.2 Hz, H-6′b), 3.69 (1H, m, H-5′), 3.03 (1H,
m, H-5R), 2.96 (1H, dtd, J 14S,15 ) 13.6, J 15,20 ) 3J 14R,15 ) 5.0,
4J 15,17 ) 2.6 Hz, H-15), 2.70 (2H, m, H2-6), 2.27 (1H, ddd,
2J 14R,14S ) 13.6, 3J 14R,15 ) 4.9, 3J 3,14R ) 2.8 Hz, H-14proR), 2.18
3
3
(18) Haasnoot, C. A. G.; de Leeuw, F. A. A. M.; Altona, C. Tetrahedron
1980, 36, 2783.
(19) Aydin, R., Gu¨nther, H. Magn. Res. Chem. 1990, 28, 448-457.
(20) van Beuzekom, A. A.; de Leeuw, F. A. A. M.; Altona, C. Magn. Reson.
Chem. 1990, 28, 68-74.
(21) (a) Schwarcz, J . A.; Cyr, N.; Perlin, A. Can. J . Chem. 1975, 53, 1872-
1875. (b) Bock, K.; Pedersen, K. Acta Chem. Scan. 1977, B31, 354-
358. (c) Parella, T.; Sanchez-Ferrando, F.; Virgili, A. Magn. Res. Chem.
1994, 32, 657-664.
(22) Bandyopadhyay, T.; Wu, J .; Stripe, W. A.; Carmichael, I.; Serianni,
A. S. J . Am. Chem. Soc. 1997, 119, 1737-1744.
(23) Kocsis, AÄ .; Pa´l, Z.; Szabo´, L.; Te´te´nyi, P.; Varga-Bala´zs, M. Eur. Pat.
Appl. EP 156267, October 2, 1985; Chem. Abstr. 1986, 104, 149345q.
(24) Heckendorf, A. H.; Mattes, K. C.; Hutchinson, C. R.; Hagaman, E.
W.; Wenkert, E. J . Org. Chem. 1976, 41, 2045-2047.
2
3
(1H, td, J 14R,14S
H-14proS), 2.07, 1.99, 1.88, 1.20 (each 3H, s, CH3CO). 1.82
)
3J 14S,15 ) 13.6 Hz, J 3,14S ) 5.5 Hz,
3
3
3
3
(1H, dtd, J 19b,20 ) 9.7, J 19a,20 ) J 15,20 ) 5.2, J 20,21 ) 1.8 Hz,
2
3
3
H-20), 1.54 (1H, dqd, J 19a,19b ) 14.2, J 18,19 ) 7.5, J 19a,20
)
2
3
5.2 Hz, H-19a), 1.22 (1H, ddq, J 19a,19b ) 14.2, J 19b,20 ) 9.7,
3J 18,19 ) 7.5 Hz, H-19b), 1.02 (3H, t, J 18,19 ) 7.5 Hz, H3-18);
3
further H coupling constants determined in C6D6, 5J 3,6R ) 1.0,
1
5J 3,6â ) 2.5, J 5R,5â ) 13.0, J 5R,6R ) 5.2, J 5R,6â ) 12.5, J 5â,6R
)
)
2
3
3
3
1.0, 3J 5â,6â ) 6.0, 2J 6R,6â ) 15.3, 3J 1′,2′ ) 8.2, 3J 2′,3′ ) 9.9, 3J 3′,4′
9.5, J 4′,5′ ) 9.9; 13C NMR (CDCl3, 100 MHz) δ 170.6, 170.0,
3
169.5, 169.0 (each CH3CO), 164.9s (C-22), 146.9d (C-17), 136.1s
NP990150R