Structural features of n-acylcytisines

Article abstract of DOI:10.1007/s10600-010-9495-7

N-Acyl cytisine derivatives were synthesized by acylation with acetic anhydride; benzoyl and o-bromo- and p-nitrobenzoyl chlorides; and crotonyl and cinnamoyl chlorides. The structures of the synthesized compounds were studied using IR, PMR, and x-ray str

Full text of DOI:10.1007/s10600-010-9495-7

Chemistry of Natural Compounds, Vol. 45, No. 6, 2009
STRUCTURAL FEATURES OF N-ACYLCYTISINES
N. P. Abdullaev, U. S. Makhmudov,* B. Tashkhodzhaev,
G. Genzhemuratova, M. G. Levkovich,
and Kh. M. Shakhidoyatov
UDC 747.945+547.79+548.737
N-Acyl cytisine derivatives were synthesized by acylation with acetic anhydride; benzoyl and o-bromo- and
p-nitrobenzoyl chlorides; and crotonyl and cinnamoyl chlorides. The structures of the synthesized compounds
were studied using IR, PMR, and x-ray structure analysis (XSA). PMR spectra of the N-acylcytisines in
solution typically had two rotational isomers around the N12–CO bond. Conformational analysis was
performed using XSA for the position of the acyl group relative to the cytisine core. Bond lengths and angles
of the acyl groups involved in the conjugation were analyzed.
Key words: alkaloids, cytisine derivatives, IR spectroscopy, PMR spectroscopy, x-ray structure analysis.
The broad spectrum of biological activity of cytisine (1) and its derivatives [1, 2] makes them a promising class for
practical application. On the other hand, the chiral 3,7-diazobicyclo[3.3.1]nonane skeleton is interesting for studying structural
features of substituted cytisines [3–6]. Until now, a large number of cytisine derivatives with various groups on the N atom
have been synthesized [7–12], including acryloyl groups [13], thiazoles, benzthiazoles [11], and 1,2,4-thiadiazole groups [12].
In continuation of our research on transformations of 1 [11, 12] and in order to find biologically active compounds in this
series, we synthesized acyl derivatives via acylation of 1 with acetic anhydride and acid chlorides. The acylating agents were
acetic anhydride; benzoyl- and o-bromo- and p-nitrobenzoyl chlorides; and crotonyl and cinnamoyl chlorides. The reaction
with acetic anhydride occurred with an excess of it. Acylation by the acid chlorides occurred in anhydrous toluene under
reflux:
O
13
12
5
7
14
NH
N
R
(CH CO) O
C
3
2
11
A
B
1
3
N
N
RCOCl, toluene
9
1
10
O
O
2 - 7
R = -ÑH (2); -Ñ H (3); -Ñ H -Br-o (4); -C H -NO -n (5); -CH=CH-C H (6); -CH=CH-CH (7)
3
6
5
6
4
6
4
2
6
5
3
Acylation of 1 by acid chlorides was carried out without a HCl acceptor. Atom N12 of ring C played this role.
Structures of 2–7 were confirmed by IR and PMR spectra and by an x-ray structure analysis (XSA) for N-o-bromobenzoylcytisine
(4), N-p-nitrobenzoylcytisine (5), and N-crotonylcytisine (6).
–1
IR spectra contained absorption bands at 1643–1653 cm (ν ) and 1634–1647 (ν ). The physicochemical properties
CO
CO
of 2, 3, and 7 agreed with those published. PMR spectra of the N-acylcytisines in solution characteristically showed several
rotational isomers around the N12–CO and CO–R bonds. They could produce spectra of several conformers or simply give
very broad spectral lines because the barriers to rotation were small. In several instances resonances could not be unambiguously
assigned.
S. Yu. Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan,
Tashkent, fax: (99871) 120 64 75, e-mail: Graf_Sharp@yahoo.com. Translated from Khimiya Prirodnykh Soedinenii, No. 6,
pp. 702–707, November–December, 2009. Original article submitted April 6, 2009.
©
0009-3130/09/4506-0837 2009 Springer Science+Business Media, Inc.
837

C18
C17
C19
C4
C3
C2
C20
C5
C6
O2
C15
C16
Br1
C14
N1
C10
C13
C7
O14
N12
C11
C8
Ñ9
4
5
6
Fig. 1. Molecular structures of 4–6.
The PMR spectrum of 3 was studied in most detail. A characteristic of this compound was that all resonances in
CHCl at room temperature (20–22°C) were very strongly broadened and overlapped so much that only resonances of H-3,
3
H-5, H-9, and the methylene pair H-8 could be identified individually. Heating the sample to 58°C and the accelerated rotation
around the N–CO bond because of this caused all resonances to narrow. The chemical shifts from all chemical groups in the
molecule could be determined. However, the presence of the barrier to rotation was still observed from the very characteristic
resonances of methylene protons H-11 and H-13. The axial components of these methylene proton pairs appeared as two
completely resolved doublets with J = 12.5 Hz at about 3.10 ppm. The equatorial protons of these methylenes formed one
common resonance at ~4.3 ppm with a width of about 80 Hz.
The positions of the resonances for the benzoyl aromatic protons in this spectrum were unusual. The α-protons of the
aromatic ring at 58°C appeared as a poorly resolved doublet of doublets (J = 8.0 and 2.0 Hz) at 6.92 ppm. The other aromatic
protons together with H-4 of cytisine itself resonated at ~7.24 ppm as a complicated 4H multiplet. The unusual position of the
resonance for the benzoyl α-protons was apparently due to the conjugation of its carbonyl with N12 of cytisine.
X-ray structure analyses of 4–6 were performed in order to establish reliably the structures of the synthesized
compounds. The results allowed most PMR resonances of the synthesized N-acyl cytisine derivatives to be assigned.
The XSA showed that 4 crystallized without solvent; 5, as a hemihydrate; 6, as a monohydrate. Figure 1 shows the
molecular structures of 4–6 in the crystals in approximately the same projection (perpendicular to the plane of C7, C9,
C11, C13 of ring C). The cytisine core in these derivatives had the same conformation. Pseudoaromatic ring A was planar
°
°
(within 0.01 Afor 4; 0.03, 5; 0.01, 6). The next six-membered ring B adopted the chair conformation ( 0.04A, 4; 0.06,
°
5; 0.02, 6) with C8 deviating from the plane of the other five atoms by 0.72 A(4), 0.74 (5), and 0.74 (6). The third six-
membered ring C adopted an ideal chair conformation.
However, PMR spectra of the N-acylcytisines showed that the acyl groups tended to form rotational isomers. For this
reason it seemed interesting to perform a stereochemical analysis of the conformationally fluxional acyl groups.
2
Atom N12 in these cytisine derivatives has sp hybridization because the unshared electron pair of N12 is conjugated
to the π-electrons of the C14 carbonyl, which is evident in the torsion angles C11–N12–C14–C15 (179.2°, 177.6, and 178.8)
and the sum of the bond angles around N12 (359.7°, 359.0, and 359.8 in 4–6, respectively) (Table 1). The C14=O14 carbonyl
was also situated parallel to the plane of C11, N12, C13, and C14 in N-crotonylcytisine (7), N-betamorpholinepropionylcytisine
[3], and in other cytisine derivatives [4]. This shows that formation of the conjugated system is favored. Carbonyl C14 was
oriented such that it was syn to the other carbonyl (C2=O2) (of the two possible syn and anti orientations) (Fig. 1). Such
mutual placement of carbonyls is also characteristic of known cytisine acyl derivatives.
838

°
TABLE 1. Bond Lengths (A) and Angles (°) in 4–6
Bond
Angle
C6-N1-C2
4
5
6
4
5
6
Br1-C16
N1-C6
N1-C2
N1-C10
O2-C2
O14-C14
N12-C14
N12-C13
N12-C11
C14-C15
C6-C5
1.895(5)
1.369(5)
1.395(6)
1.485(5)
1.232(6)
1.229(5)
1.348(6)
1.447(5)
1.463(6)
1.498(6)
1.349(6)
1.512(6)
1.379(6)
1.403(7)
1.435(7)
1.541(6)
1.522(6)
1.509(7)
1.520(7)
1.400(7)
1.399(8)
1.529(7)
1.342(8)
1.377(11)
1.399(11)
1.353(9)
122.7(4)
122.6(4)
114.6(4)
125.1(4)
119.9(4)
114.6(4)
123.1(4)
118.8(4)
118.1(4)
120.1(4)
120.7(4)
119.1(4)
117.9(5)
124.4(4)
117.5(4)
119.7(4)
124.8(5)
115.5(4)
110.1(3)
111.5(3)
108.1(3)
110.0(4)
114.9(3)
106.6(3)
120.0(4)
121.6(5)
120.6(4)
117.8(4)
110.1(4)
112.6(4)
110.6(4)
110.2(3)
121.4(4)
118.8(6)
120.4(4)
120.3(6)
120.0(6)
121.5(5)
123.6(4)
122.2(4)
114.1(4)
125.8(4)
119.8(4)
113.4(4)
123.5(5)
118.0(5)
118.5(4)
118.8(5)
121.5(5)
119.6(4)
119.9(5)
121.6(5)
118.3(5)
119.6(4)
126.0(5)
114.4(5)
109.4(4)
111.7(4)
107.8(4)
110.0(4)
114.4(4)
106.3(4)
119.9(5)
120.2(5)
122.49(18)
122.76(17)
114.50(17)
126.7(2)
119.4(2)
113.61(19)
120.7(2)
120.3(2)
119.0(2)
119.3(2)
122.0(2)
118.7(2)
1.387(6)
1.413(6)
1.494(6)
1.237(6)
1.232(6)
1.363(6)
1.471(6)
1.482(6)
1.533(7)
1.367(7)
1.520(6)
1.392(7)
1.398(8)
1.434(7)
1.540(7)
1.539(7)
1.518(7)
1.526(7)
1.410(8)
1.381(7)
1.530(7)
1.346(9)
1.398(7)
1.368(8)
1.397(9)
1.210(6)
1.218(6)
1.493(7)
1.375(3)
1.393(3)
1.483(3)
1.243(3)
1.231(3)
1.347(3)
1.453(3)
1.463(3)
1.485(3)
1.354(3)
1.495(3)
1.297(3)
C6-N1-C10
C2-N1-C10
C14-N12-C13
C14-N12-C11
C13-N12-C11
O14-C14-N12
O14-C14-C15
N12-C14-C15
C5-C6-N1
C5-C6-C7
N1-C6-C7
C16-C15-C20
C16-C15-C14
C20-C15-C14
O2-C2-N1
C6-C7
C15-C16
C15-C20
C2-C3
C13-C7
C7-C8
C10-C9
C8-C9
C5-C4
C16-C17
C9-C11
C3-C4
C17-C18
C18-C19
C19-C20
O4-N2
120.5(2)
1.413(3)
1.529(3)
1.518(3)
1.518(3)
1.517(4)
1.396(3)
1.459(3)
1.521(4)
1.349(4)
1.386(4)
1.382(3)
1.370(4)
118.8(2)
125.0(2)
116.2(2)
111.23(17)
110.29(18)
111.08(18)
110.3(2)
115.07(18)
106.48(19)
120.5(2)
O2-C2-C3
N1-C2-C3
N12-C13-C7
C6-C7-C8
C6-C7-C13
C8-C7-C13
N1-C10-C9
C9-C8-C7
C6-C5-C4
C15-C16-C17
C15-C16-Br1
C17-C16-Br1
C10-C9-C8
C10-C9-C11
C8-C9-C11
N12-C11-C9
C4-C3-C2
C18-C17-C16
C3-C4-C5
C17-C18-C19
C20-C19-C18
C19-C20-C15
O4-N2-O3
O4-N2-C18
O3-N2-C18
C19-C18-N2
C17-C18-N2
C20-C21-C22
C21-C20-C19
C21-C22-C17
C18-C17-C22
C22-C17-C16
129.2(2)
N2-O3
N2-C18
C17-C22
C22-C21
C20-C21
108.9(4)
113.3(4)
111.3(4)
112.4(4)
122.0(5)
118.7(5)
120.9(5)
122.5(5)
118.4(5)
120.2(5)
123.9(5)
118.1(4)
118.0(5)
118.5(5)
119.0(4)
110.4(2)
112.3(2)
110.3(2)
110.5(2)
121.6(2)
118.6(2)
120.0(2)
120.9(3)
119.5(3)
1.391(3)
1.370(4)
1.370(5)
120.8(3)
120.2(2)
120.1(3)
118.5(2)
122.9(2)
Steric repulsion between the equatorial H atom (C-13-H) and the Br atom in 4 and the aromatic C16 H atom in 5
interfered with conjugation between the π-electron systems of the aromatic ring and the C14=O14 double bond, where the
N12–C14–C15–C16 torsion angle was –71.5° and –58.5°, respectively. However, the bulky cinnamoyl group in 6, which was
°
bonded to N12, was planar (within 0.083A) and there was no stereochemical hindrance to destroy the conjugation (mesomeric
effect). Neighboring C14=O14 and C15=C16 double bonds were mutually cis oriented, as was observed in 7 [3].
839

c
b
0
c
b
0
a
a
5
4
Fig. 2. Molecular packing of 4 and 5.
c
b
0
a
Fig. 3. Molecular packing of 6.
The aforementioned mesomeric effects were also evident in the change of C14=O14, C14–N12, and C14–C15 bond
°
lengths compared with their statistical mean values. The C14 carbonyl bond lengths lengthened to 1.229(5)A, 1.232(6), and
°
1.231(3) and were comparable with those observed for C2=O2 of pseudoaromatic ring Aof 1.232(6)A, 1.238(6), and 1.243(3).
°
Heterobonds C14–N12 were shortened to 1.348(5) A, 1.363(7), and 1.347(3) in 4–6, respectively. Several bonds in 6 were
°
markedly shortened, e.g., C14–C15 [1.485(3) A], C15=C16 [1.297(3)], and C16–C17 [1.459(3)], although the C14–C15
bonds in 4 and 5 were 1.498(5) and 1.533(7), respectively. Table 1 lists bond lengths and angles involving nonhydrogen atoms
in 4–6.
Figure 2 shows the molecular packing of 4 in the crystal. The molecules are situated at van-der-Waals distances.
Noticeably shortened intermolecular contacts were not observed.
Compound 5 crystallized as a hemihydrate (Fig. 2) because the multiplicity (degree of position population) of the
water O atom in the crystal cell was 0.13. An analysis of intermolecular contacts showed that the crystal had intermolecular
°
H-bonds involving (not periodical) water and the carbonyl O of ring A (O1...O1w, 2.827A).
Figure 3 shows the molecular packing of 6 in the crystal. Compound 6 crystallized as a monohydrate. The crystal
contained intermolecular H-bonds involving the two H atoms of a water molecule according to the scheme O2...H1–O1w and
O1w–H2...O3.
The N-cinnamoylcytisine molecules formed an infinite chain of H-bonds along the b axis through the water of
°
°
crystallization. The O2...H1w–O1w H-bond parameters were O2...O1w, 2.847 A, O2...H1w, 1.92 A, O2...H1–O1w, 169°;
°
O1w–H2...O3 H-bond parameters, O1w...O3, 2.903, H2w...O3, 2.13 A, O1w–H2...O3, 162°.
840

TABLE 2. Principal Crystallographic Parameters and Characteristics of X-ray Structure Analysis for 4–6
Structure
Molecular formula
4
5
6
C18H17N2O2Br
C18H17N3O4·H2O
339.35
C20H20N2O2·H2O
338.40
MW
373.25
System
Space group
Orthorhombic
P212121
4
15.9128 (5)
10.6955 (3)
9.5252 (4)
90.00
1621.14 (10)
1.529
Orthorhombic
P212121
4
10.899 (2)
11.388 (2)
13.678 (3)
90.00
1697.7 (6)
1.328
Monoclinic
P21
2
7.7220 (15)
11.181 (2)
10.667 (2)
105.56 (3)
887.2 (3)
1.267
Z
°
, A
b,
a
°
A
°
, A
c
β
° 3
V, A
, g/cm3
ρ
Crystal size, mm
0.25×0.50×0.65
0.35×0.50×0.75
0.35×0.45×0.50
Scan range 2
θ
9.96
151.8
≤θ≤
3.6
≤θ≤
55.0
3.6 52.0
≤θ≤ °
°
°
μexp, mm–1
3.549
2709
2634
0.096
2210
1547
0.086
1836
1725
Number of reflections
Number of reflections with I>2 (I)
σ
0.0531 (0.0541)
0.1426 (0.1439)
1.006
0.0628 (0.0951)
0.1728 (0.2072)
0.969
0.0389 (0.0425)
0.0977 (0.1017)
1.157
R (I>2 (I) and total)
wR2
S
σ
1
° –3
Electron-density difference peaks, e A
0.842 and –1.359
0.165 and –0.181
0.169 and –0.244
EXPERIMENTAL
IR spectra were recorded on a Perkin–Elmer Model 2000 Fourier-IR spectrometer; PMR spectra in CDCl and CD OD
3
3
solutions, on Tesla B 567 (operating frequency 100 MHz) and Unity-400+ (operating frequency 400 MHz) spectrometers with
hexamethyldisiloxane (HMDSO) internal standard.
N-Acetylcytisine (2). Cytisine (1.9 g, 0.01 mol) was mixed with acetic anhydride (5 mL) and completely dissolved
after a certain time. The mixture was left overnight. The resulting crystals were filtered off, washed with anhydrous ether, and
dried to afford white crystals, yield 2.05 g (88.4%), mp 210°C (ether) (agreed with the literature [1]), R 0.12 (Silufol,
f
acetone:CHCl , 1:1).
3
–1
IR spectrum (KBr, ν, cm ): 3444, 3287, 3087, 3049, 2951, 2931, 1634, 1617, 1578, 1562, 1546, 1452, 1439, 1342,
1332, 1308, 1259, 1155, 1139, 796.
The PMR spectrum (100 MHz, CD OD, δ, ppm, J/Hz) at room temperature showed two conformers. Protons H-4,
3
H-5, and H-7 and the methyl gave two resonances each. Protons H-3, H-9, and both H-8 protons appeared as individual
singular resonances. Resonances of the other protons could not be assigned. 1.60 and 1.95 (3H, s, CH ), 2.05 (2H, m, H-8),
3
2.49 (1H, br.s, H-9), 2.80 and 2.93 (H, m, H-7), 6.29 (H, d, J = 7.7, H-5), 6.34 and 6.36 (H, d, J = 9.0, H-3), 7.40 and 7.43
5,4
3,4
(H, dd, J = 9.0, J = 7.7, H-4).
4,3
4,5
N-Benzoylcytisine (3). A mixture of cytisine (1.9 g, 0.01 mol) and benzoylchloride (1.55 g, 0.011 mol) in toluene
(50 mL) was refluxed for 2 h and cooled. Yield 1.56 g (53.1%). It was recrystallized from acetone:ether (1:2), R 0.53 (Silufol,
f
acetone:CHCl , 1:1), mp 116°C (agreed with the literature [1]).
3
–1
IR spectrum (KBr, ν, cm ): 3450, 3238, 3087, 3052, 2942, 2911, 1651, 1625, 1577, 1569, 1546, 1450, 1439, 1349,
1304, 1272, 1240, 1225, 1180, 807, 792.
PMR spectrum (400 MHz, CDCl , δ, ppm, J/Hz, 58°C): 1.97 (2H, m, H-8), 2.41 (1H, br.s, H-9), 2.96 (1H, br.s, H-7),
3
3.09 (1H, d, J
= 12.5, H -11*), 3.12 (1H, d, J
= 12.5, H -13*), 3.77 (1H, dd, J
= 15.7, J
= 6.3, Ha-10), 4.14
11,11
ax
13,13
ax
10,10
10,9
(H, d, J
= 15.7, Hb-10), 4.30 (2H, br.s, H -11 + H -13), 5.90 (1H, br.s, H-5), 6.48 (1H, dd, J = 9.1, J = 1.3, H-3),
10,10
eq eq 3,4 3,5
6.92 (2H, dd, J
= 8.0, J
= 2.0, Hα-benzoyl), 7.17–7.30 (4H, m, H-4, Hβ + Hγ-benzoyl).
meta
ortho
N-o-Bromobenzoylcytisine (4). The reaction was performed analogously to that above. Cytisine (1.9 g, 0.01 mol)
and o-bromobenzoylchloride (2.41 g, 0.011 mol) produced white crystals (1.5 g, 40%), mp 245-246°C, R 0.15 (Silufol,
f
benzene:acetone, 2:1).
841

–1
IR spectrum (KBr, ν, cm ): 3052, 2941, 1717, 1651, 1626, 1563, 1482, 1422, 1368, 1323, 1256, 1168, 1144, 816,
771.
The PMR spectrum (100 MHz, CDCl , δ, ppm, J/Hz) at room temperature showed highly broadened resonances that
3
overlapped each other. This prevented unambiguous assignment for some of them. 2.00 (2H, m, H-8), 2.30 and 2.60 (1H, br.s,
H-9), ~3.00 (1H, br.s, H-7), 5.70 and 6.10 (1H, d, J = 7.0, H-5), 6.30 (1H, m, Hα-benzoyl), 6.46 (1H, d, J = 9.0, H-3),
5,4
3,4
6.75–7.60 (4H, m, H-4, Hβ + Hγ-benzoyl).
N-p-Nitrobenzoylcytisine (5). A mixture of cytisine (1.9 g, 0.01 mol) and p-nitrobenzoylchloride (2.04 g,
0.011 mol) in toluene (50 mL) was refluxed for 2 h and cooled. The resulting crystals were filtered off, washed with water, and
dried. It was recrystallized from acetone:hexane to give shiny white crystals, yield 1.9 g (56%), mp 205–206°C, R 0.51
f
(Silufol, acetone:CHCl , 1:1).
3
–1
IR spectrum (KBr, ν, cm ): 3444, 3253, 3097, 3052, 2945, 2917, 1653, 1634, 1598, 1568, 1543, 1474, 1456, 1431,
1347, 1306, 1270, 1244, 1160, 802, 770.
The PMR spectrum (100 MHz, CD OD, δ, ppm, J/Hz) at room temperature showed that all resonances were highly
3
broadened. 2.10 (2H, m, H-8), 2.40 and 2.60 (1H, br.s, H-9), 3.15 (1H, m, H-7), 6.05 (1H, br.d, J = 7.0, H-5), 6.50 (1H,
5,3
dd, J = 9.0, J = 1.5, H-3), 7.00 (2H, br.d, J
~ 8.0, Hα-benzoyl), 7.45 (1H, m, H-4), 8.15 (2H, br.d, J
~ 8.0,
3,4
3,5
ortho
ortho
Hβ-benzoyl).
N-Cinnamoylcytisine (6) was synthesized analogously as above from cytisine (1.9 g, 0.01 mol) and cinnamoylchloride
(1.83 g, 0.011 mol) in toluene (50 mL) to afford 6 (1.58 g, 45%), mp 119–120°C (benzene:hexane, 1:3), R 0.18 (Silufol,
f
benzene:acetone, 2:1), lit. [7] mp 104°C.
–1
IR spectrum (KBr, ν, cm ): 3483, 3420, 3049, 2939, 1643, 1584, 1562, 1547, 1499, 1457, 1440, 1360, 1312, 1276,
1155, 810, 771.
The PMR spectrum (100 MHz, CDCl , δ, ppm, J/Hz) showed that only the resonances for methylene H-11 and H-13
3
were highly broadened. 2.00 (2H, m, H-8), 2.48 (1H, br.s, H-9), 2.90–3.30 (3H, m, H-7, H -11, H -13), 3.80 (1H, dd,
ax
ax
J
J
= 16.0, J
= 7.0, Ha-10), 4.13 (1H, d, J
= 16.0, Hb-10), 4.37 (2H, br.s, H -11 + H -13), 6.04 (1H, dd, J = 7.0,
10,10
10,9
10,10 eq eq 5,4
= 1.5, H-5), 6.37 (1H, dd, J = 8.0, J = 1.3, H-3), 6.54 (1H, d, J
= 16.0, H-1′), 7.20–7.45 (7H, m, H-4, H-2′, H
).
arom
5,3
3,4
3,5
1′,2′
N-Crotonylcytisine (7). A solution of cytisine (1.9 g, 0.01 mol) and crotonylchloride (1.055 g, 1.15 mL = 0.011 mol)
in anhydrous toluene was refluxed for 2 h and cooled. The product was obtained as an oil that crystallized upon standing,
mp 115–116°C (benzene:hexane, 1:3), lit. [7] mp 112–114°C, R 0.20 (Silufol, benzene:acetone, 2:1), yield 1.29 g (50%).
f
–1
IR spectrum (oil, ν, cm ): 3432, 3059, 2992, 2942, 1707, 1660, 1651, 1645, 1634, 1567, 1548, 1494, 1429, 1348,
1274, 1162, 1142, 887, 800, 751.
The PMR spectrum (100 MHz, CDCl , δ, ppm, J/Hz) showed that only methylene protons H-11 and H-13 were
3
highly broadened. 1.72 (3H, dd, J
H -11, H -13), 3.75 (1H, dd, J
= 7.7, J
= 16.0, J
= 1.5, H-3′), 1.98 (2H, m, H-8), 2.45 (1H, br.s, H-9), 3.05 (3H, br.s, H-7,
3′,2′
3′,1′
= 6.0, Ha-10), 4.08 (1H, d, J
= 15.7, Hb-10), 4.30 (2H, br.s, H -11,
10,10 eq
ax
ax
10,10
10,9
H -13), 5.95 (1H, d, J
= 17.0, H-1′), 6.01 (1H, dd, J = 7.0, J = 1.5, H-5), 6.35 (1H, dd, J = 8.0, J = 1.5, H-3), 6.60
eq
1′,2′
5,4 5,3 3,4 3,5
(1H, dq, J
= 17.0, J
= 7.7, H-2′), 7.20 (1H, dd, J = 8.0, J = 7.0, H-4).
2′,1′
2′,3′ 4,3 4,5
X-ray StructureAnalyses. Single crystals for XSAwere produced by slow evaporation from the appropriate solvents
at room temperature. Unit-cell constants of 4 were determined and refined on a CCD Xcalibur diffractometer (Oxford
Diffraction); of 5 and 6, on a Stoe Stadi-4 diffractometer (300 K, graphite monochromator). Table 2 lists the principal parameters
of the XSAand the calculations. Athree-dimensional data set of reflections was collected on the same respective diffractometers
with ω/2ω-scanning using Cu K -radiation for 4 and Mo K -radiation for 5 and 6. Absorption corrections were applied for the
α
α
structure of 4 using the Multi-scan method and were not applied for 5 and 6.
Structures of 4–6 were solved by direct methods using the SHELXS-97 programs and were refined using the
2
SHELXL-97 program. All nonhydrogen atoms were refined by full-matrix least-squares methods (over F ). Positions of H
atoms in the structures of 4 and 6 were found geometrically and refined with fixed isotropic thermal parameters U = nU ,
iso
eq
where n = 1.2 for all types of H atoms and U was the equivalent isotropic thermal parameter of the corresponding C atom.
eq
All H atoms in the structure of 5 and the H atoms of the water of crystallization in the structure of 6 were found from difference
electron-density (ED) syntheses. The difference ED syntheses of the structure of 5 during refinement showed a distinct peak
located at nonbonding distance from the molecule. Designating this as an O atom from a water molecule, the multiplicity was
refined and gave a value of 0.13. This indicated that 5 was a hemihydrate. The H atoms could not be found experimentally.
842

Data from the XSA were deposited as CIF files in the Cambridge Crystallographic Data Centre (CCDC 736505,
736506, 736507 for 4–6, respectively).
ACKNOWLEDGMENT
The work was financed by the KKRNT RU program for Basic Scientific Research, Grant FA-F3-T045.
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