Crystal structures of dihydroquercetin 3-acetate and dihydroquercetin 3,3',4',7-tetraacetate: Hydrogen bonding in 5-hydroxyflavanones

Article abstract of DOI:10.1139/v99-140

The molecular structures of dihydroquercetin 3-acetate 3 and dihydroquercetin 3,3'.4',7-tetraacetate 4 were determined by single crystal X-ray analysis. Comparison of their crystal data with those, of 16 known 5-hydroxyflavanones shows intramolecular O(5)

Full text of DOI:10.1139/v99-140

1436
Crystal structures of dihydroquercetin 3-acetate
and dihydroquercetin 3,3′,4′,7-tetraacetate:
hydrogen bonding in 5-hydroxyflavanones
Eberhard Kiehlmann, Kumar Biradha, Konstantin V. Domasevitch,
and Michael J. Zaworotko
Abstract: The molecular structures of dihydroquercetin 3-acetate 3 and dihydroquercetin 3,3′,4′,7-tetraacetate 4
were determined by single crystal X-ray analysis. Comparison of their crystal data with those of 16 known
5-hydroxyflavanones shows intramolecular O(5)-H···O(4)=C hydrogen bonding, preference for nearly perpendicular
orientation of the two aromatic rings and preferred sofa conformation of the heterocyclic ring. The major stabilizing
force in the crystal packing pattern of 3 is intermolecular hydrogen bonding.
Key words: crystal structure, dihydroquercetin, flavanones, hydrogen bonding.
Résumé : On a déterminé les structures moléculaires du 3-acétate de dihydroquercétine (3) et du 3,3′,4′,7-tétraacétate
de dihydroquercétine (4) par diffraction des rayons X sur des cristaux uniques. Une comparaison de leurs structures
cristallines avec celles de seize autres 5-hydroxyflavones connues démontre l’existence d’une liaison hydrogène
intramoléculaire O(5)-H···O(4)=C, d’une préférence pour une orientation pratiquement perpendiculaire des deux noyaux
aromatiques et d’une préférence pour la conformation sofa du cycle hétérocyclique. La liaison hydrogène
intramoléculaire est la principale force stabilisante dans le patron d’empilement cristallin du composé 3.
Mots clés : structure cristalline, dihydroquercétine, flavones, liaison hydrogène.
[Traduit par la Rédaction] Kiehlmann et al. 1443
Introduction
exhaustive acetylation of (+)-dihydroquercetin with excess
acetic anhydride and pyridine (8, 9) and subsequent
deacetylation of the pentaacetate 2 with sodium sulfite in
aqueous methanol (4) (Scheme 1). Integration of its
1H NMR spectrum showed the product to be a mono-
acetate, with the following characteristic proton chemical
shifts (in Me2CO-d6) indicating the presence of an aliphatic
rather than an aromatic ester: δ 1.96 (3-OAc, vs. 2.26 and
2.28 for ArOAc of 2 and 4), 5.82 (H-3, vs. 4.4–4.8 for 3-
CHOH of 1), and 11.57 ppm (5-OH, H-bonded to >C=O).
The absolute configurations of 3 and 4 follow from their
optical activity, the proven stereochemistry of the (+)-dhq
(10) used as starting material, and the known retention of
configuration at the chiral centers during mild base-
catalyzed O-acetylation (11) and O-deacetylation (12) of
flavonoids.
The 3,3′,4′,7-tetraacetate 4 is obtained as major acetylation
product of dhq when only catalytic amounts of pyridine are
used as base catalyst (4, 8). It can be readily separated from
the pentaacetate 2 formed as byproduct by crystallization
from methanol. Contrary to a previous literature report (2),
acid-catalyzed deacetylation of 2 yields the isomeric
3,3′,4′,5-tetraacetate. The structure with the free hydroxyl
Dihydroflavonols (2-aryl-3-hydroxy-2,3-dihydrobenzopyran-
4-ones) are widely distributed in the plant kingdom and ex-
hibit a large variety of physiological effects (1). Dihydr-
oquercetin (3,3′,4′,5,7-pentahydroxyflavanone, 1) (dhq), the
most common member of this group of flavonoids, occurs in
Douglas fir bark and has been found in O-methylated, O-ac-
etylated, and glycosidic forms in many other plants. The
close similarity in the chemical and spectral properties of
various partially derivatized dhq isomers has led to inconsis-
tent and erroneous structural (2) and spectral assignments
(3) in the past. Following the synthesis of 22 of the 31 possi-
ble dhq acetates (4), we now report the crystal parameters of
dhq 3-acetate 3 and dhq 3,3′,4′,7-tetraacetate 4, the only two
that yielded single crystals of sufficient size for X-ray
diffraction studies, and compare them to those of 16 known
5-hydroxyflavanones.
Discussion
(2R,3R)-Dihydroquercetin 3-acetate 3, the sweet princi-
ple of several subtropical plants (3, 5–7), was prepared by
Received February 15, 1999.
E. Kiehlmann.1 Department of Chemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
K. Biradha. Department of Chemistry, Saint Mary’s University, Halifax, NS B3H 3C3, Canada.
K.V. Domasevitch and M. Zaworotko. Department of Chemistry, University of Winnipeg, 515 Portage Avenue, Winnipeg, MB
R3B 2E9, Canada.
1Author to whom correspondence may be addressed. Telephone: (604) 291-4880. Fax: (604) 291-3765. e-mail: ekie@sfu.ca
Can. J. Chem. 77: 1436–1443 (1999)
© 1999 NRC Canada

Kiehlmann et al.
1437
Scheme 1.
OH
OH
4'
OAc
OAc
6'
1
B
1
3'
HO
O
9
AcO
O
O
2
7
2'
A
C
O
excess Ac2O
excess pyridine
3
10
OH
4
OAc
5
2
OH
OAc
excess
Ac2O
Na2SO3
pyridine
(cat.)
aq.MeOH
OAc
OH
OH
AcO
O
HO
O
OAc
OAc
OAc
4
3
OH
O
OH
O
group at C-5 (4, systematic name: (2R,3R)-3,7-bis(acetyloxy)-
2-[3,4-bis(acetyloxy)phenyl]-2,3-dihydro-5-hydroxy-4H-1-ben-
zopyran-4-one) was first proposed by Aft (8, 13) on the
basis of IR- and UV-spectral evidence and is consistent with
the results of our NMR and X-ray crystallographic studies.
Comparison of the chemical shifts of its aromatic protons
and C-13 nuclei with those of 2 and other flavanone acetates
(4, 14) shows that the A-ring is monoacetylated, and the
downfield position and sharpness of the OH peak
than a parallel alignment because it minimizes repulsive
steric interactions between the ortho hydrogens (H-2′ and H-
6′) and the bulky 3-acetoxy substituent. The 5-OH proton is
displaced by 0.18 Å from the O5-CCC-O4 mean plane, and
the large C5-O5-H bond angle of 136(5)° places it into a rel-
atively unfavorable position for efficient intramolecular hy-
drogen bonding to the carbonyl oxygen (O4) via a puckered
six-membered ring. Intermolecular hydrogen bonding forces,
on the other hand, are strong (O···H distances <2.0 Å) and
account for the stability of the crystal. They involve the 3′-,
4′-, and 7-OH groups as donors, 4′-OH, 5-OH, and the ester
carbonyl as acceptors, and the water of hydration. Each wa-
ter molecule is tetrahedrally connected to two others and
two phenolic OH groups: one links OH-4′ and OH-7, the
other OH-3′ and OH-5 of adjacent organic moieties (Fig. 2).
In addition, a hydrogen bond between OH-4′ and the car-
bonyl oxygen of the acetoxy group links molecules related
by the screw axis. The H-bonding parameters are summa-
rized in Tables 1 and 2.
1
(11.35 ppm in Me2CO-d6, 11.28 ppm in CDCl3) in the H
NMR spectrum are typical of a strongly hydrogen-bonded
proton. Since this proton exchanges slowly, it broadens the
signals of adjacent C-13 nuclei, a feature which has been
previously exploited for the unambiguous assignment of ter-
tiary and quaternary carbons in the 13C NMR spectra of 5-
hydroxyflavanones (15, 16) and 5-hydroxyisoflavones (17).
Thus, in the proton-coupled 13C NMR spectrum of 4, the
broad singlet at 163.8 ppm must be assigned to the
hydroxyl-substituted C-5, the sharp triplet at 160.1 ppm to
the acetoxy-substituted C-7 (coupled to H-6 and H-8) and
The tetraacetate 4 crystallizes in the triclinic P1 space
group and exhibits three-center bifurcated hydrogen bond-
ing. Its asymmetric unit comprises two residues (Fig. 3). In
the crystal lattice, each hydroxyl proton is hydrogen-bonded
to two pyranone carbonyl oxygen atoms (one intra-, the
other intermolecularly), and each of the carbonyl oxygens in
turn is surrounded by two hydroxyl protons. Although the
hydrogen atoms are positioned slightly above the O5-CCC-
O4 plane (as in 3), the smaller C5-O-H angles of 116(4)°
and 98(4)° (vs. 136° for 3) indicate that in this case intra-
molecular attractive forces predominate. The heterocyclic
ring adopts a half-chair conformation with C-2 above (0.46,
0.47 Å) and C-3 below (–0.25, –0.41 Å) the mean plane de-
fined by the A-ring, O-1 and C-4. As in 3, ring B is nearly
orthogonal (75°, 73°) to ring A, and the two hydrogens of
ring C are again trans-diaxial. Large Ar-OCO (63°–90°) and
small ArO-CO torsional angles (2°–10°), as found in most
aryl acetate crystal structures (18), suggest that the lone
electron pairs of the three acetylated phenolic oxygens are
delocalized mainly into the carbonyl groups. Crystal data,
the broad triplet at 105.8 ppm to C-4a. Likewise, the broad-
3
ened double doublet at 104.5 ppm (1J = 166 Hz, JH8
=
3.8 Hz) is due to C-6 and can be readily distinguished from
the sharp C-8 double doublet at 102.9 ppm.
Single-crystal X-ray diffraction analysis confirmed the
structure of 3 as trans-2-(3,4-dihydroxyphenyl)-2,3-dihydro-
3-acetoxy-5,7-dihydroxy-4H-1-benzopyran-4-one, with one
organic molecule and two molecules of water comprising the
asymmetric unit (Fig. 1). The 3-acetoxy group and the B-
ring are linked to the pyranone ring equatorially (angle C1′-
C2-C3-OAc 64°), placing H-2 and H-3 into trans-diaxial po-
1
sition, in good agreement with the large H NMR coupling
constant (J23 = 12.0 Hz) observed in solution. The
heterocyclic ring adopts a sofa conformation, with C-2 as
the only atom deviating significantly (by 0.61 Å; C-3 devi-
ates by 0.04 Å) from the mean plane defined by O-1, the six
carbon atoms of the A-ring and C-4. The plane of the pen-
dant catechol ring (B) forms a torsional angle of 73° with
the A-ring. This appears to be energetically more favorable
© 1999 NRC Canada

1438
Can. J. Chem. Vol. 77, 1999
Fig. 1. ORTEP diagram of 3 with atomic numbering scheme.
Fig. 2. Packing diagram of 3 (projection on the bc plane).Hydrogen bonds are represented by broken lines. Not shown (for clarity of
presentation) are additional hydrogen bonds from O(8) to H(3′O), O(4′) to H(9O), and O(31) to H(4′O). The water molecules form an
infinite network, with bulky flavanones attached as pendants.
© 1999 NRC Canada

Kiehlmann et al.
1439
Table 1. Intermolecular hydrogen-bonding in dhq acetates 3 and 4.a
Distances (Å)
D---A
Angle (°)
D-H---A
Hydrogen
atom, H
Compd.
Donor, D
Acceptor, A
D—H
H---A
3
O(5)
O(7)
O(3′)
O(4′)
O(8)
O(8)
O(9)
O(9)
O(5A)
O(5B)
H(5O)
H(7O)
O(7) (x, 1+y, z)
O(9) (1+x, y, 1+z)
O(8)
O(31) (1–x, –0.5+y, 1–z)
O(5) (2–x, –0.5+y, 2–z)
O(9) (1+x, y, z)
0.83(9)
0.90(8)
0.81(6)
0.76(5)
0.83(7)
0.77(6)
1.02(14)
0.83(8)
0.89(8)
1.02(9)
3.187(8)
2.705(8)
2.747(9)
2.670(7)
2.870(10)
2.791(9)
2.733(9)
2.790(10)
2.934(8)
2.875(8)
2.20(8)
1.84(8)
1.95(7)
1.94(5)
2.09(8)
2.05(8)
1.73(13)
1.99(8)
2.48(8)
2.08(8)
150(7)
163(8)
165(6)
159(6)
159(7)
167(8)
160(11)
161(7)
112(6)
133(6)
H(3′O)
H(4′O)
H(82O)
H(81O)
H(91O)
H(92O)
H(5OA)
H(5OB)
O(4′)
O(8) (1–x, –0.5+y, 1–z)
O(4B) (–1+x, y, –1+z)
O(4A) (1+x, y, 1+z)
4
aIntramolecular hydrogen bonds are listed in Table 2.
Fig. 3. ORTEP diagram of 4 with atomic numbering scheme. Perspective projection of the dimeric moiety, with 40% probability
thermal ellipsoids. The acetyl groups attached to atoms O(3′A), O(4′A), O(3′B), and O(4′B) are omitted for clarity.
erences that are common to this class of compounds and
applicable to both the solid and solution state.
structure refinement parameters, and selected bond lengths
and angles of 3 and 4 are listed in Tables 3 and 4, the re-
fined atomic coordinates in Tables 5–7.
The Cambridge Crystallographic Database2 contains 16 5-
hydroxy-flavanones: 10 (5a–j, Scheme 2) (19) with and 6
(16, 20) without hydrogen coordinates. Comparison of their
crystal parameters with those of 3 and 4 (Table 2) permits
the following generalizations about the conformational pref-
The pyranone ring prefers the sofa over the half-chair
conformation in all compounds except 4, 5b, and 5e. In
silybin (5k, R3 = OH, R3′-R4′ = O-CH(CH2OH)-CHAr-O,
ref. 20a) and uvarinol (5l, R8 = 2-hydroxybenzyl, R6 = 2-
hydroxy-5-(2-hydroxybenzyl)-benzyl, ref. 20b), one residue
of the asymmetric unit is a slightly distorted sofa, the other a
half-chair, demonstrating the flexible response of the
2 Cambridge Crystallographic Data Centre (CCDC), http://www.ccdc.cam.ac.uk (see footnote 4 for address).
© 1999 NRC Canada

1440
Can. J. Chem. Vol. 77, 1999
heterocyclic ring to packing forces. In all cases, H-2 and H-
3 are trans-diaxial, and except for hesperetin hydrate (5c)
and naringin hydrate (5e), the plane of the equatorial B-ring
is oriented nearly perpendicular (71–113°) to that of the A-
ring.
Strong intramolecular hydrogen bonding with planar six-
membered ring geometry (21) is characteristic of all 5-
hydroxyflavanones. The OH(5)···O(4) distances are short
(1.43–1.92 Å), the bond angles at the hydrogen atom have a
mean value of 143° (esd 9°), and the Ar-OH torsional angles
are close to zero (1°–12°). In addition, all molecules with
extra phenolic hydroxyl groups form intermolecular hydro-
gen bonds. The carbonyl oxygen of each of the nine anhy-
drous compounds accepts two OH protons in bifurcated
fashion, while in the three hydrated structures 3, 5c, and 5e,
water serves as acceptor, and the 5-OH proton is engaged in
three-center hydrogen bonding. Thus, in the presence of wa-
ter, inter- rather than intramolecular hydrogen bonding ap-
pears to determine the crystal geometry. Hesperetin hydrate
5c is the only structure that may also be stabilized by aro-
matic ring stacking: its two benzene rings lie in the same
plane, and successive molecular layers are approximately
3.6 Å apart.
Experimental
Acetylation of (+)-dhq, extracted from Douglas fir bark as
described previously (22), with excess acetic anhydride in
the presence of a catalytic amount of pyridine (4) gave the
3,3′,4′,7-tetraacetate 4 in 50% yield, mp 144–6° (MeOH).
Proton-coupled 13C NMR (Bruker AMX-400, chemical shifts
relative to Me2CO-d6 at 29.80) δ (ppm): 169.4 (3-OAc),
2
168.7–168.4 (ArOAc), 163.8 (br, C-5), 162.6 (d, J = 4 Hz,
2
C-8a), 160.1 (t, J = 4 Hz, C-7), 144.2/143.4 (C-3′/4′), 134.9
2
3
(br d, J = 9 Hz, C-1′), 126.4/124.7/124.0 (1J = 164 Hz, J =
3
4/8 Hz, H-2′/5′/6′), 105.8 (br t, J = 5 Hz, C-4a), 104.5 (br
1
3
1
dd, J = 166 Hz, J = 4 Hz, C-6), 102.9 (dd, J = 169 Hz,
3J = 4.6 Hz, C-8), 81.1 (m, J = 151 Hz, C-2), 73.3 (dd, J =
1
1
2
147 Hz, J = 2.3 Hz, C-3), 21.0 (q, J = 130 Hz, 7-OAc),
20.5 (q, J = 130 Hz, 3′/4′-OAc), and 20.1 (q, J = 130 Hz,
3-OAc). MS (HP-5985 quadrupole instrument) m/z (% inten-
sity): 472 (0.7, M), 412 (1.3, M – HOAc), 388 (1.7, M – 2
ketene), 370 (3.1, M – ketene – HOAc), 346 (3.5, M – 3
ketene), 328 (14.4, M – 2 ketene – HOAc), 286 (24.3, M –
HOAc – 3 ketene), 250 (4.5, M – ring B – CHO), 237 (3.0),
236 (3.6, RDA fragment with ring B – ketene), 223 (3.8),
208 (7.8), 195 (25.1), 194 (20.3, RDA fragment with ring
A), 192 (15.1), 153 (100), 152 (73.8, RDA fragment with
ring A – ketene), 150 (54.1, (HO)2C6H3CH=CO+·), 123
+
(20.9, (HO)2C6H3CH2 ). [α]2D2 +41° (Autopol II polarimeter,
c 1.07, Me2CO) (lit. (8) +18.6°, c 1.07). (2R,3R)-Dihydro-
quercetin 3-acetate 3 was obtained in 70% yield by deacetyl-
ation of the pentaacetate 2 with sodium sulfite in aqueous
methanol (41 h/25°) as described previously (4), pale yellow
needles, mp 125–7° (aq. MeOH).
Crystal structure determination
The X-ray diffraction data for 3 and 4 were collected on a
Siemens SMART/CCD diffractometer equipped with an
LT-II low-temperature device, using monochromatic Mo Kα
radiation (λ = 0.710 73 Å). Diffracted data were corrected
© 1999 NRC Canada

Kiehlmann et al.
1441
Table 3. Crystal data and structure refinement parameters for 3 and 4.
3
4
Empirical formula
Formula weight
C17H18O10 (C17H14O8·2H2O)
382.32
C23H20O11
472.41
Temperature (°C)
–70 ± 2
–60 ± 2
Crystal system
Monoclinic
Triclinic
Space group
P21
P1
Unit cell: a (Å)
b, c (Å)
α, β, γ (deg)
Cell volume (Å3)
Density (calculated) (g cm–3)
Absorption coefficient (mm–1)
F(000)
9.1036(14)
5.5715(6)
13.1685(13), 15.428(2)
85.599(2), 89.629(2), 80.368(2)
1112.7(2)
1.410 (Z = 2)
0.114
492
7.8843(11), 12.705(2)
90, 99.888(3), 90
898.4(2)
1.413 (Z = 2)
0.118
400
Crystal size (mm)
0.20 × 0.15 × 0.15
1.63–25.00
3690
2784 (R(int) = 0.0413)
1618
2784/1/276
0.25 × 0.20 × 0.20
1.31–27.94
6244
5296 (R(int) = 0.0300)
3073
5296/3/621
θ range for data collection (°)
Reflections collected
Independent reflections
Observed reflections (I > 2σ(I))
Data/restraints/parameters
Goodness-of-fit on F2
Final Ra indices (obs.)
Ra indices (all data)
Largest diff. peak and hole (e Å–3)
0.971
0.965
R1 = 0.0772, wR2b = 0.1397
R1 = 0.1471, wR2b = 0.1679
0.231 and –0.224
R1 = 0.0705, wR2b = 0.1628
R1 = 0.1267, wR2b = 0.1927
0.271 and –0.233
aR = Σ|Fo| – |Fc|/Σ|Fo|.
2
2
b1/w = [σ2(Fo ) + (aP)2 + bP] where 3P = (Fo + 2Fc2); a and b are constants adjusted by the program.
Table 4. Selected bond distances (Å) and angles (deg) (X = H or Ac).
Distance
3
4A
4B
Angle
3
4A
4B
O(1)—C(9)
O(1)—C(2)
O(3)—C(3)
O(4)—C(4)
O(5)—C(5)
O(7)—C(7)
O(7)—X
1.388(7)
1.452(8)
1.450(8)
1.229(8)
1.331(9)
1.343(9)
0.90(8)
1.359(9)
1.446(8)
1.429(8)
1.226(9)
1.351(9)
1.417(9)
1.320(10)
1.326(11)
1.380(10)
1.516(10)
1.493(10)
1.514(11)
1.431(10)
1.396(10)
1.435(10)
1.367(8)
1.451(8)
1.446(7)
1.221(8)
1.338(9)
1.397(9)
1.323(10)
1.365(9)
1.358(9)
1.520(10)
1.518(9)
1.515(9)
1.467(9)
1.440(10)
1.381(10)
C(9)-O(1)-C(2)
O(1)-C(2)-C(3)
O(3)-C(3)-C(4)
C(2)-C(3)-C(4)
O(4)-C(4)-C(10)
O(4)-C(4)-C(3)
C(10)-C(4)-C(3)
C(9)-C(10)-C(4)
C(9)-C(10)-C(5)
C(4)-C(10)-C(5)
O(5)-C(5)-C(6)
O(5)-C(5)-C(10)
C(5)-O(5)-H
115.9(6)
108.9(5)
109.6(6)
112.6(6)
124.5(7)
120.1(7)
115.4(7)
122.1(7)
116.2(7)
121.6(7)
120.5(7)
119.2(8)
136(5)
115.3(5)
109.4(6)
111.5(6)
110.3(6)
124.2(7)
120.7(7)
114.8(7)
119.8(7)
118.2(6)
122.0(7)
115.7(8)
121.7(7)
98(4)
116.1(5)
107.0(5)
108.1(5)
107.6(5)
124.8(7)
122.2(6)
112.8(6)
121.3(7)
118.4(6)
119.9(7)
119.3(7)
122.4(6)
116(4)
O(3Ј)—X
0.81(6)
0.76(5)
O(4Ј)— X
C(2)—C(1Ј)
C(2)—C(3)
C(3)—C(4)
C(4)—C(10)
C(10)—C(5)
C(9)—C(10)
1.488(9)
1.501(10)
1.518(10)
1.419(10)
1.446(10)
1.409(10)
C(7)-O(7)-X
O(1)-C(9)-C(10)
125(6)
119.7(7)
118.1(7)
121.7(6)
120.8(7)
120.8(6)
for absorption using the SADABS program, SHELXTL was
used for the structure solution,3 and full-matrix least-squares
refinement was based on F2. All the non-hydrogen atoms
were refined anisotropically. Hydrogen atoms attached to
carbon were fixed at calculated positions and refined
isotropically on the basis of corresponding C-atoms (U(H) =
1.2 Ueq (C)); those of O-H groups were located and refined
isotropically. Pertinent crystallographic details are given in
Tables 3–6. Supplementary tables of crystal structure and re-
finement, atomic coordinates, bond lengths and angles,
anisotropic thermal parameters, and hydrogen coordinates
have been deposited.4
3 G.M. Sheldrick. SADABS. Univ. Göttingen, 1996; SHELXTL, Release 5.03. Siemens Analytical X-ray Instruments Inc., Madison, Wis.
1994.
4 Supplementary material may be purchased from: The Depository of Unpublished Data, Document Delivery, CISTI, National Research
Council Canada, Ottawa, Canada, K1A 0S2. With the exception of tables of displacement parameters, these have also been deposited with
the Cambridge Crystallographic Data Centre and can be obtained on request from: The Director, Cambridge Crystallographic Data Centre,
University Chemical Laboratory, 12 Union Road, Cambridge, CB2 1EZ, U.K.
© 1999 NRC Canada

1442
Can. J. Chem. Vol. 77, 1999
Table 5. Atomic coordinates (× 104) and equivalent isotropic
displacement parameters (Å2 × 103) for refined atoms of 3.
U(eq) is defined as one third of the trace of the orthogonalized
Uij tensor.
Table 6. Atomic coordinates (× 104) and equivalent isotropic
displacement parameters (Å2 × 103) for refined atoms of
molecule 4A. U(eq) is defined as one third of the trace of the
orthogonalized Uij tensor.
x
y
z
U(eq)
38(1)
x
y
z
U(eq)
O(1)
O(31)
O(3)
O(4)
O(5)
7206(5)
6461(5)
5826(5)
8110(6)
9736(7)
9996(6)
5904(5)
2947(5)
8929(7)
784(6)
7446(6)
12137(7)
11793(6)
12219(6)
10892(8)
4919(7)
7034(9)
7535(7)
6591(8)
5105(10)
8787(9)
10457(9)
10763(11)
9283(9)
9376(11)
7932(11)
6355(10)
6198(9)
9254(3)
7158(4)
8768(4)
10429(4)
12132(5)
12267(5)
5167(4)
4812(4)
5696(5)
4418(4)
8934(5)
9005(5)
10098(6)
10659(5)
11696(6)
12224(5)
11753(6)
10751(5)
10244(5)
7854(5)
7044(5)
6030(5)
5812(5)
6590(5)
7617(5)
7787(5)
7601(6)
11900(60)
12950(60)
5400(50)
4340(40)
5390(50)
6280(60)
4580(100)
4540(60)
O(1A)
O(31A)
O(3A)
O(4A)
O(5A)
O(7A)
O(3′A)
O(4′A)
O(3′1)
O(4′1)
O(71A)
C(2A)
C(3A)
C(4A)
C(10A)
C(5A)
C(6A)
C(7A)
C(8A)
C(9A)
C(1′A)
C(2′A)
C(3′A)
C(4′A)
C(5′A)
C(6′A)
C(3′1)
C(3′2)
C(4′1)
C(4′2)
C(31A)
C(32A)
C(71A)
C(72A)
H(5OA)
6675(9)
3340(11)
977(10)
3344(3)
6091(5)
5145(4)
4020(4)
2506(4)
722(4)
5253(3)
3908(4)
4656(3)
3257(4)
2425(3)
3759(4)
6936(4)
8178(3)
6079(8)
8708(3)
4012(10)
5122(5)
4720(5)
3852(5)
3825(4)
3124(5)
3104(6)
3817(5)
4508(5)
4537(5)
5981(5)
6093(5)
6822(5)
7473(5)
7386(5)
6648(5)
6514(8)
6642(9)
8756(5)
9401(5)
4156(5)
3989(6)
3808(9)
3697(8)
2558(44)
43(1)
74(2)
51(1)
53(1)
55(2)
53(2)
56(2)
51(1)
163(5)
54(1)
181(6)
49(2)
52(2)
45(2)
35(2)
46(2)
53(2)
46(2)
42(2)
41(2)
43(2)
50(2)
44(2)
48(2)
46(2)
54(2)
87(3)
106(4)
50(2)
60(2)
50(2)
67(3)
83(3)
82(3)
47(22)
49(2)
36(1)
45(1)
41(2)
37(1)
56(2)
39(1)
42(2)
42(2)
31(2)
34(2)
34(2)
26(2)
33(2)
34(2)
25(2)
30(2)
31(2)
26(2)
38(2)
37(2)
33(2)
36(2)
34(2)
37(2)
52(2)
50(30)
60(30)
18(18)
6(17)
20(30)
40(30)
170(60)
40(30)
1746(10)
4262(11)
11472(9)
8065(10)
4527(10)
5877(20)
8149(11)
9491(16)
5159(14)
2795(14)
3226(15)
5318(14)
5763(15)
7714(15)
9289(14)
9008(13)
7019(14)
4978(14)
6540(15)
6440(14)
4781(15)
3261(15)
3378(16)
7637(22)
9632(21)
6455(17)
6009(18)
1369(16)
–935(17)
11326(19)
13770(16)
3334(147)
O(7)
O(3′)
O(4′)
O(8)
O(9)
C(2)
C(3)
C(4)
C(10)
C(5)
C(6)
6731(4)
6515(4)
7926(6)
5718(4)
–568(6)
4349(6)
4237(6)
3776(5)
2984(5)
2371(6)
1580(6)
1440(5)
2025(5)
2799(5)
4843(6)
5525(6)
6063(6)
5892(6)
5201(6)
4662(6)
7660(8)
8258(8)
6380(6)
7170(6)
5976(6)
6736(6)
–271(7)
–963(7)
3086(55)
6128(8)
6928(8)
7864(8)
8426(8)
9377(8)
9888(7)
9513(7)
8634(8)
8105(7)
5297(7)
6049(7)
5291(7)
3757(7)
3000(7)
3751(7)
5655(8)
4362(8)
9700(80)
10390(80)
6760(70)
3340(60)
9410(70)
9210(80)
1760(140)
950(80)
C(7)
C(8)
C(9)
7643(10)
8363(9)
C(1′)
C(2′)
C(3′)
C(4′)
C(5′)
C(6′)
C(31)
C(32)
H(5O)
H(7O)
H(3′O)
H(4′O)
H(81O)
H(82O)
H(91O)
H(92O)
7841(10)
7566(11)
7814(11)
8304(10)
8569(9)
12466(10)
13632(11)
11860(110)
4870(110)
6830(80)
7370(70)
6040(90)
6130(90)
5780(180)
4080(100)
Scheme 2.
R6'
O
R4'
a) R3 = R3' = R4' = OH,
R8
R2' = R6' = R8 = prenyl (PIJCIU)
b) R3 = OAc, R6 = Me (JEDVAP)
c) R3' = OH, R4' = OMe (FOYTOC)
d) R4' = OH (DOLRIF)
R7O
R3'
R2'
R6
R3
e) R4' = OH, R7= glyc (TAFBEH)
f) R4' = OH, R7= Me (JESGET)
g) R4' = OMe, R7= Me (SATDAS)
h) R7 = Me (KEDDAY)
5
OH
O
All R=H except as listed
( with CCDC RefCode)
i) R6 = R8 = Me (FUNWUG)
j) R6 = OMe, R7= Me (RAVMIK)
© 1999 NRC Canada

Kiehlmann et al.
1443
Table 7. Atomic coordinates (× 104) and equivalent isotropic
displacement parameters (Å2 × 103) for refined atoms of
molecule 4B. U(eq) is defined as one third of the trace of the
orthogonalized Uij tensor.
4. E. Kiehlmann. Org. Prep. Proced. Int. 31, 87 (1999).
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7. S. Öksüz and G. Topçu. Phytochemistry, 31, 195 (1992).
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9. K. Weinges, R. Kolb, and P. Kloss. Phytochemistry, 10, 829
(1971).
10. J.W. Clark-Lewis and W. Korytnyk. J. Chem. Soc. 2367
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K.-i. Tomita, Acta Crystallogr. Sect. C: Cryst. Struct.
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Sect. C: Cryst. Struct. Commun. 46, 1969 (1990); (g) C.O.
Miles, L. Main, and B.K. Nicholson. Acta Crystallogr. Sect. C:
Cryst. Struct. Commun. 45, 681 (1989); (h) M. Shoja. Z.
Kristallogr. 189, 89 (1989); (i) N. Tanrisever, F.R. Fronczek,
N.H. Fischer, and G.B. Williamson. Phytochemistry, 26, 175
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Ponglimanont, C. Pakawatchai, H.-K. Fun, and K. Sivakumar.
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and J. Clardy. J. Org. Chem. 44, 4709 (1979); (c) K.
Chantrapromma, C. Pakawatchai, B.W. Skelton, A.H. White,
and S. Worapatamasri. Aust. J. Chem. 42, 2289 (1989); (d) P.
Narayanan, K. Zechmeister, M. Rohrl, and W. Hoppe. Acta
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Yamagata, G.-Z. Jin, and K. Tomita. Chem. Pharm. Bull. 42,
1143 (1994).
x
y
z
U(eq)
O(1B)
O(31B)
O(3B)
O(4B)
O(5B)
O(7B)
O(3′B)
O(4′B)
O(3′3)
O(4′3)
O(71B)
C(2B)
C(3B)
C(4B)
C(10B)
C(5B)
C(6B)
C(7B)
C(8B)
C(9B)
C(1′B)
C(2′B)
C(3′B)
C(4′B)
C(5′B)
C(6′B)
C(3′3)
C(3′4)
C(4′3)
C(4′4)
C(31B)
C(32B)
C(71B)
C(72B)
H(5OB)
4538(9)
8453(11)
9924(9)
9474(10)
7228(11)
–127(10)
3160(9)
4229(3)
1005(4)
2302(3)
3457(4)
5095(4)
6870(4)
1118(4)
1127(4)
–215(5)
2041(4)
8177(5)
3628(5)
2959(5)
3672(5)
4590(5)
5233(5)
6006(5)
6144(5)
5553(5)
4792(5)
3012(5)
2365(5)
1762(5)
1807(6)
2476(6)
3069(5)
122(6)
9737(3)
11090(4)
10342(3)
11710(3)
12510(4)
11207(4)
8119(4)
6794(3)
8750(7)
6204(3)
10998(9)
9611(4)
10447(4)
11152(5)
11117(5)
11837(5)
11837(5)
11181(5)
10455(5)
10451(4)
8826(5)
8819(5)
8143(5)
7466(5)
7455(5)
8145(5)
8464(7)
8479(10)
6211(5)
43(1)
60(2)
41(1)
53(2)
56(2)
52(2)
55(2)
53(2)
117(3)
50(1)
161(5)
40(2)
33(2)
38(2)
43(2)
39(2)
43(2)
39(2)
44(2)
34(2)
40(2)
42(2)
44(2)
44(2)
49(2)
39(2)
65(3)
122(6)
45(2)
73(3)
39(2)
55(2)
62(2)
91(4)
63(24)
6587(11)
5737(13)
3118(10)
1796(15)
6930(13)
7604(11)
7889(14)
5983(14)
5673(14)
3645(15)
2004(13)
2275(14)
4287(13)
6754(14)
5002(14)
4958(14)
6515(14)
8212(15)
8285(14)
3770(16)
1541(23)
4721(16)
4999(19)
10126(14)
12676(14)
–43(16)
–392(8)
1317(6)
492(7)
1347(5)
785(6)
7872(7)
8491(6)
4581(61)
5585(7)
10765(5)
10803(6)
11152(7)
11355(8)
12442(48)
–2350(17)
8799(159)
Acknowledgements
We thank the Natural Sciences and Engineering Research
Council of Canada and St. Mary’s University for financial
support.
References
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1986. Edited by J.B. Harborne. Chapman & Hall, London.
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(1959).
21. M.C. Etter. Acc. Chem. Res. 23, 120 (1990).
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3. F. Bohlmann, C. Zdero, M. Grenz, A.K. Dhar, H. Robinson,
and R.M. King. Phytochemistry, 20, 281 (1981).
© 1999 NRC Canada