Two (E,E)- and (Z,E)-thiazol-5-ylpenta-2,4-dienones

In order to characterize the structural elements that might play a role in non-covalent DNA binding by the antitumor antibiotic leinamycin, we have solved the crystal structures of the two leinamycin analogs, methyl (R)-5-{2-[1-(tert-butoxy­carbonyl­amino)­ethyl]­thia­zol-4-yl}penta-(E,E)-2,4-dienoate, C₁₆H₂₂N₂O₄S, (II), and 2-methyl-8-oxa-16-thia-3,17-di­aza­bicyclo­[12.2.1]­heptadeca-(Z,E)-1(17),10,12,14-tetraene-4,9-di­one, C₁₄H₁₆N₂O₃S, (III). The penta-2,4-dienone moiety in both of these analogs adopts a conformation close to planarity, with the thia­zole ring twisted out of the plane by 12.9 (2)° in (II) and by 21.4 (4)° in (III).

S1. Comment

Leinamycin, (I), is a natural product with promising antitumor activity (Hara et al., 1989, 1990). This activity is believed to result from the ability of the compound to damage cellular DNA (Hara et al., 1990; Asai et al., 1996; Mitra et al., 1997; Breydo et al., 2001). Leinamycin has a unique structure, with an unusual 1,2-dithiolan-3-one 1-oxide moiety connected by a spiro linkage to an 18-membered macrocycle. This antibiotic is capable of both DNA alkylation and oxidative DNA damage (Gates, 2000). \sch

Recent studies showing that leinamycin does not efficiently alkylate single-stranded DNA suggest that non-covalent association of leinamycin with the double helix facilitates DNA alkylation by the antibiotic (Asai et al., 1996; Breydo et al., 2002). It seems likely that the macrocycle of leinamycin plays a major role in non-covalent binding of the compound to DNA. Thus, in order to understand better the nature of the interaction between leinamycin and DNA, it is important to characterize the three-dimensional structure of the thiazol-5-yl-penta-2,4-dienone fragment of the antibiotic. Although crystal structures of leinamycin and several of its derivatives have been solved previously (Hirayama & Matsuzawa, 1993; Kanda et al., 1999), the coordinates for these structures have not been published.

As a part of an investigation of non-covalent DNA binding by leinamycin, we prepared several E,E- and Z,E-thiazol-5-yl-penta-2,4-dienones. Here, we present the crystal structures of methyl (R)-5-{2-[1-(tert-butoxycarbonylamino)ethyl]thiazol-4-yl}-penta-(E,E)- 2,4-dienoate, (II), and 2-methyl-8-oxa-16-thia-3,17-diazabicyclo[12.2.1]heptadeca(Z,E)- 1(17),10,12,14-tetraene-4,9-dione, (III). Our results provide the first detailed structural information regarding leinamycin analogs containing the thiazol-5-yl-penta-2,4-dienone moiety.

The structures of (II) and (III) reveal that the penta-2,4-dienone fragment is nearly planar [to within 0.02 Å for (II) and 0.05 Å for (III)], similar to the known structures of compounds containing an α,β,γ,δ-conjugated carbonyl group (Cox, 1994; Rabinovich & Schmidt, 1967). The bond lengths in the penta-2,4-dienone system indicate conjugation (Ladd & Palmer, 1993; Wiberg et al., 1991) between the double bonds and with the thiazole ring. The thiazole ring is twisted out of plane relative to the penta-2,4-dienone moiety, by 12.9 (2)° in (II) and by 21.4 (4)° in (III) (PLATON; Spek, 2001). Presumably, this twist serves to minimize steric repulsion between the lone pair on the thiazole N atom and an adjacent H atom [H12 in (II) or H11 in (III)]. This assumption is supported by a comparison with the known structure of epothilone B, (IV) (Hoefle et al., 1996). Epothilone B contains an alkene moiety in the C4 position of the thiazole ring that is also slightly twisted out of plane. Although coordinates for the crystal structure of leinamycin are not available, the graphical representations that have been published (Hirayama & Matsuzawa, 1993) indicate that the antibiotic also adopts a conformation with a nearly planar penta-2,4-dienone moiety and the thiazole ring twisted slightly out of plane.

The 18-membered macrocycle of leinamycin clearly presents a large hydrophobic surface that may drive association of the natural product with the hydrophobic major groove of duplex DNA (Jadhav et al., 1999). In addition, it is possible that the conjugated thiazol-5-yl-penta-2,4-dienone moiety found in leinamycin may represent a novel type of DNA intercalator where, individual double bonds are a part of the intercalating system. Several examples of such small intercalators are known and include esperamycin A1 (Yu et al., 1994), C-1027 (Yu et al., 1995), and amiloride (Bailly et al., 1993). The results reported here may provide important structural information that will ultimately help us understand the detailed nature of the non-covalent interactions between leinamycin and DNA.

S2. Experimental

Compounds (II) and (III) were prepared from (R)—N-Boc alanine, and their synthesis will be described separately. Racemization of compound (III) occurred in the course of the synthesis. Crystals suitable for X-ray diffraction analysis were obtained by slow evaporation of dichloromethane solutions of the compounds.

S3. Refinement

H atoms were placed at calculated positions and were updated with each cycle of refinement, but not refined. The C—H distances were fixed in the range 0.95–1.00 Å and N—H distances were fixed at 0.88 Å. The displacement parameters were fixed at 1.2 times the equivalent isotropic factor for the parent atom.

Computing details

For both compounds, data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1998); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Burnett & Johnson, 1996); software used to prepare material for publication: CIFTAB (Sheldrick, 1997).

Figures

	Fig. 1. A view of the molecule of (II) showing 50% probability displacement ellipsoids. H atoms are drawn as small spheres of arbitrary radii.
	Fig. 2. A view of the molecule of (III) showing 50% probability displacement ellipsoids. H atoms are drawn as small spheres of arbitrary radii.

(II) Methyl (R)-5-{2-[1-(tert-butoxycarbonylamino)ethyl]-thiazol-4-yl}-penta- (E,E)-2,4-dienoate

Crystal data

C16H22N2O4S	Z = 1
Mr = 338.42	F(000) = 180
Triclinic, P1	Dx = 1.278 Mg m^−3
a = 5.207 (2) Å	Mo Kα radiation, λ = 0.71070 Å
b = 5.876 (3) Å	Cell parameters from 2894 reflections
c = 15.339 (7) Å	θ = 2.7–27.1°
α = 82.21 (1)°	µ = 0.20 mm^−1
β = 81.43 (1)°	T = 173 K
γ = 72.17 (1)°	Prism, yellow
V = 439.8 (3) Å^3	0.45 × 0.35 × 0.35 mm

Data collection

Bruker SMART CCD area-detector diffractometer	2820 independent reflections
Radiation source: fine-focus sealed tube	2702 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.019
ω scans	θmax = 27.1°, θmin = 1.4°
Absorption correction: multi-scan (SADABS; Blessing, 1995)	h = −6→6
Tmin = 0.89, Tmax = 0.94	k = −7→7
3484 measured reflections	l = −19→16

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.035	H-atom parameters constrained
wR(F^2) = 0.100	w = 1/[σ^2(Fo^2) + (0.0665P)^2 + 0.0536P] where P = (Fo^2 + 2Fc^2)/3
S = 1.12	(Δ/σ)max < 0.001
2820 reflections	Δρmax = 0.25 e Å^−3
213 parameters	Δρmin = −0.26 e Å^−3
3 restraints	Absolute structure: Flack (1983); 908 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.07 (7)

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > 2σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
S1	0.87448 (9)	0.75876 (8)	0.47934 (5)	0.03525 (16)
O1	0.6765 (3)	0.6049 (3)	0.77640 (12)	0.0341 (4)
N1	0.6938 (4)	0.4313 (3)	0.43791 (13)	0.0266 (4)
C1	0.8123 (4)	0.4810 (4)	0.49867 (16)	0.0253 (4)
O2	0.4359 (3)	0.4865 (3)	0.68712 (13)	0.0372 (4)
N2	0.8903 (4)	0.4308 (3)	0.65545 (14)	0.0304 (4)
H2	1.0354	0.4565	0.6701	0.037*
C2	0.6438 (5)	0.6189 (4)	0.37076 (16)	0.0282 (5)
O3	−0.0892 (4)	0.0388 (3)	0.15064 (14)	0.0439 (5)
C3	0.7319 (5)	0.8076 (4)	0.38194 (19)	0.0341 (5)
H3	0.7166	0.9472	0.3414	0.041*
O4	−0.0580 (5)	0.3922 (4)	0.08202 (15)	0.0538 (6)
C4	0.9104 (4)	0.3065 (4)	0.57729 (16)	0.0272 (4)
H4	0.7934	0.1964	0.5915	0.033*
C5	0.6475 (4)	0.5067 (4)	0.70538 (16)	0.0281 (5)
C6	0.4403 (5)	0.6928 (4)	0.84305 (16)	0.0305 (5)
C7	1.2047 (5)	0.1543 (4)	0.55458 (17)	0.0313 (5)
H7A	1.3239	0.2583	0.5435	0.047*
H7B	1.2176	0.0736	0.5015	0.047*
H7C	1.2605	0.0338	0.6043	0.047*
C8	0.2299 (5)	0.9053 (4)	0.79992 (19)	0.0373 (5)
H8A	0.3203	1.0204	0.7675	0.056*
H8B	0.0923	0.9842	0.8459	0.056*
H8C	0.1427	0.8472	0.7588	0.056*
C9	0.5663 (6)	0.7775 (5)	0.9114 (2)	0.0436 (6)
H9A	0.6966	0.6395	0.9396	0.065*
H9B	0.4231	0.8539	0.9565	0.065*
H9C	0.6600	0.8934	0.8821	0.065*
C10	0.3274 (6)	0.4908 (5)	0.8847 (2)	0.0416 (6)
H10A	0.2356	0.4454	0.8415	0.062*
H10B	0.1972	0.5436	0.9363	0.062*
H10C	0.4759	0.3522	0.9034	0.062*
C11	0.5037 (5)	0.6039 (4)	0.29702 (17)	0.0314 (5)
H11	0.5043	0.7176	0.2467	0.038*
C12	0.3743 (5)	0.4392 (4)	0.29608 (18)	0.0303 (5)
H12	0.3715	0.3272	0.3468	0.036*
C13	0.2394 (5)	0.4215 (4)	0.22320 (17)	0.0316 (5)
H13	0.2354	0.5379	0.1736	0.038*
C14	0.1191 (5)	0.2518 (4)	0.22068 (17)	0.0325 (5)
H14	0.1203	0.1346	0.2699	0.039*
C15	−0.0152 (5)	0.2409 (4)	0.14385 (18)	0.0334 (5)
C16	−0.2147 (7)	0.0087 (5)	0.0766 (2)	0.0479 (7)
H16A	−0.3802	0.1423	0.0696	0.072*
H16B	−0.2609	−0.1431	0.0876	0.072*
H16C	−0.0879	0.0065	0.0224	0.072*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0336 (3)	0.0298 (3)	0.0470 (4)	−0.0127 (2)	−0.0057 (3)	−0.0106 (2)
O1	0.0238 (8)	0.0504 (9)	0.0312 (9)	−0.0110 (7)	0.0002 (7)	−0.0184 (7)
N1	0.0256 (9)	0.0277 (8)	0.0280 (10)	−0.0085 (7)	−0.0043 (8)	−0.0052 (7)
C1	0.0201 (10)	0.0262 (9)	0.0305 (12)	−0.0081 (7)	0.0028 (9)	−0.0094 (8)
O2	0.0230 (8)	0.0555 (10)	0.0378 (10)	−0.0137 (7)	−0.0012 (7)	−0.0186 (8)
N2	0.0228 (9)	0.0446 (10)	0.0287 (11)	−0.0124 (8)	−0.0016 (8)	−0.0151 (8)
C2	0.0241 (11)	0.0276 (9)	0.0303 (12)	−0.0042 (8)	−0.0002 (9)	−0.0050 (9)
O3	0.0563 (12)	0.0407 (9)	0.0398 (11)	−0.0155 (8)	−0.0178 (9)	−0.0046 (8)
C3	0.0287 (12)	0.0275 (10)	0.0444 (15)	−0.0059 (9)	−0.0021 (10)	−0.0053 (10)
O4	0.0709 (15)	0.0630 (12)	0.0378 (11)	−0.0326 (11)	−0.0230 (11)	0.0088 (10)
C4	0.0247 (11)	0.0344 (10)	0.0268 (11)	−0.0118 (8)	−0.0025 (9)	−0.0102 (9)
C5	0.0246 (11)	0.0351 (10)	0.0272 (12)	−0.0097 (8)	−0.0041 (9)	−0.0076 (9)
C6	0.0269 (11)	0.0395 (11)	0.0253 (12)	−0.0077 (9)	0.0002 (9)	−0.0112 (9)
C7	0.0270 (11)	0.0357 (11)	0.0307 (13)	−0.0066 (9)	−0.0024 (9)	−0.0090 (9)
C8	0.0365 (13)	0.0383 (11)	0.0361 (14)	−0.0077 (10)	−0.0057 (11)	−0.0056 (10)
C9	0.0333 (14)	0.0640 (16)	0.0358 (14)	−0.0098 (12)	−0.0037 (11)	−0.0236 (13)
C10	0.0409 (14)	0.0437 (13)	0.0375 (15)	−0.0115 (11)	−0.0003 (11)	−0.0009 (11)
C11	0.0269 (11)	0.0323 (11)	0.0313 (12)	−0.0038 (8)	−0.0043 (9)	−0.0013 (9)
C12	0.0243 (11)	0.0342 (11)	0.0294 (13)	−0.0031 (8)	−0.0041 (9)	−0.0038 (9)
C13	0.0256 (11)	0.0384 (11)	0.0276 (12)	−0.0035 (9)	−0.0036 (9)	−0.0055 (9)
C14	0.0305 (12)	0.0358 (11)	0.0275 (12)	−0.0035 (9)	−0.0047 (9)	−0.0031 (9)
C15	0.0287 (12)	0.0418 (12)	0.0297 (12)	−0.0079 (9)	−0.0019 (10)	−0.0100 (10)
C16	0.0531 (18)	0.0556 (15)	0.0423 (16)	−0.0177 (13)	−0.0128 (14)	−0.0170 (13)

Geometric parameters (Å, º)

S1—C3	1.717 (3)	C7—H7B	0.9800
S1—C1	1.738 (2)	C7—H7C	0.9800
O1—C5	1.347 (3)	C8—H8A	0.9800
O1—C6	1.484 (3)	C8—H8B	0.9800
N1—C1	1.300 (3)	C8—H8C	0.9800
N1—C2	1.393 (3)	C9—H9A	0.9800
C1—C4	1.515 (3)	C9—H9B	0.9800
O2—C5	1.220 (3)	C9—H9C	0.9800
N2—C5	1.357 (3)	C10—H10A	0.9800
N2—C4	1.461 (3)	C10—H10B	0.9800
N2—H2	0.8800	C10—H10C	0.9800
C2—C3	1.363 (3)	C11—C12	1.340 (3)
C2—C11	1.460 (3)	C11—H11	0.9500
O3—C15	1.343 (3)	C12—C13	1.437 (4)
O3—C16	1.447 (3)	C12—H12	0.9500
C3—H3	0.9500	C13—C14	1.338 (4)
O4—C15	1.205 (3)	C13—H13	0.9500
C4—C7	1.534 (3)	C14—C15	1.475 (4)
C4—H4	1.0000	C14—H14	0.9500
C6—C10	1.508 (4)	C16—H16A	0.9800
C6—C9	1.524 (3)	C16—H16B	0.9800
C6—C8	1.533 (3)	C16—H16C	0.9800
C7—H7A	0.9800
C3—S1—C1	88.99 (11)	C6—C8—H8B	109.5
C5—O1—C6	120.41 (18)	H8A—C8—H8B	109.5
C1—N1—C2	110.92 (18)	C6—C8—H8C	109.5
N1—C1—C4	123.65 (18)	H8A—C8—H8C	109.5
N1—C1—S1	114.85 (17)	H8B—C8—H8C	109.5
C4—C1—S1	121.34 (16)	C6—C9—H9A	109.5
C5—N2—C4	119.94 (18)	C6—C9—H9B	109.5
C5—N2—H2	120.0	H9A—C9—H9B	109.5
C4—N2—H2	120.0	C6—C9—H9C	109.5
C3—C2—N1	114.5 (2)	H9A—C9—H9C	109.5
C3—C2—C11	125.5 (2)	H9B—C9—H9C	109.5
N1—C2—C11	120.0 (2)	C6—C10—H10A	109.5
C15—O3—C16	115.5 (2)	C6—C10—H10B	109.5
C2—C3—S1	110.8 (2)	H10A—C10—H10B	109.5
C2—C3—H3	124.6	C6—C10—H10C	109.5
S1—C3—H3	124.6	H10A—C10—H10C	109.5
N2—C4—C1	111.60 (18)	H10B—C10—H10C	109.5
N2—C4—C7	109.83 (18)	C12—C11—C2	123.9 (2)
C1—C4—C7	110.38 (19)	C12—C11—H11	118.1
N2—C4—H4	108.3	C2—C11—H11	118.1
C1—C4—H4	108.3	C11—C12—C13	124.1 (2)
C7—C4—H4	108.3	C11—C12—H12	117.9
O2—C5—O1	125.9 (2)	C13—C12—H12	117.9
O2—C5—N2	123.7 (2)	C14—C13—C12	124.2 (2)
O1—C5—N2	110.34 (18)	C14—C13—H13	117.9
O1—C6—C10	110.7 (2)	C12—C13—H13	117.9
O1—C6—C9	102.49 (19)	C13—C14—C15	122.1 (2)
C10—C6—C9	110.1 (2)	C13—C14—H14	119.0
O1—C6—C8	109.3 (2)	C15—C14—H14	119.0
C10—C6—C8	113.4 (2)	O4—C15—O3	122.8 (2)
C9—C6—C8	110.3 (2)	O4—C15—C14	125.6 (2)
C4—C7—H7A	109.5	O3—C15—C14	111.6 (2)
C4—C7—H7B	109.5	O3—C16—H16A	109.5
H7A—C7—H7B	109.5	O3—C16—H16B	109.5
C4—C7—H7C	109.5	H16A—C16—H16B	109.5
H7A—C7—H7C	109.5	O3—C16—H16C	109.5
H7B—C7—H7C	109.5	H16A—C16—H16C	109.5
C6—C8—H8A	109.5	H16B—C16—H16C	109.5
C2—N1—C1—C4	−175.7 (2)	C6—O1—C5—N2	−177.63 (19)
C2—N1—C1—S1	−0.3 (2)	C4—N2—C5—O2	−3.2 (4)
C3—S1—C1—N1	−0.47 (18)	C4—N2—C5—O1	176.76 (18)
C3—S1—C1—C4	175.11 (19)	C5—O1—C6—C10	60.5 (3)
C1—N1—C2—C3	1.1 (3)	C5—O1—C6—C9	177.9 (2)
C1—N1—C2—C11	−178.0 (2)	C5—O1—C6—C8	−65.1 (3)
N1—C2—C3—S1	−1.5 (3)	C3—C2—C11—C12	−166.7 (2)
C11—C2—C3—S1	177.62 (18)	N1—C2—C11—C12	12.4 (3)
C1—S1—C3—C2	1.07 (19)	C2—C11—C12—C13	−179.1 (2)
C5—N2—C4—C1	79.8 (3)	C11—C12—C13—C14	177.3 (2)
C5—N2—C4—C7	−157.4 (2)	C12—C13—C14—C15	−179.6 (2)
N1—C1—C4—N2	−147.7 (2)	C16—O3—C15—O4	2.5 (4)
S1—C1—C4—N2	37.1 (2)	C16—O3—C15—C14	−178.0 (2)
N1—C1—C4—C7	89.9 (3)	C13—C14—C15—O4	−8.9 (4)
S1—C1—C4—C7	−85.3 (2)	C13—C14—C15—O3	171.6 (2)
C6—O1—C5—O2	2.3 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O2^i	0.88	2.20	3.072 (3)	170

Symmetry code: (i) x+1, y, z.

(III) 2-methyl-8-oxa-16-thia-3,17-diazabicyclo[12.2.1]heptadeca-(Z,E)- 1(17),10,12,14-tetraene-4,9-dione

Crystal data

C14H16N2O3S	F(000) = 308
Mr = 292.35	Dx = 1.355 Mg m^−3
Monoclinic, Pc	Mo Kα radiation, λ = 0.71073 Å
a = 10.078 (1) Å	Cell parameters from 2334 reflections
b = 8.882 (1) Å	θ = 2.3–27.0°
c = 8.512 (1) Å	µ = 0.23 mm^−1
β = 109.89 (1)°	T = 173 K
V = 716.5 (1) Å^3	Plate, colorless
Z = 2	0.4 × 0.3 × 0.1 mm

Data collection

Bruker SMART CCD area-detector diffractometer	2391 independent reflections
Radiation source: fine-focus sealed tube	2177 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.023
ω scans	θmax = 27.1°, θmin = 2.2°
Absorption correction: multi-scan (SADABS; Blessing, 1995)	h = −12→12
Tmin = 0.77, Tmax = 0.98	k = −10→11
4350 measured reflections	l = −10→8

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.030	H-atom parameters constrained
wR(F^2) = 0.070	w = 1/[σ^2(Fo^2) + (0.0425P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 1.00	(Δ/σ)max = 0.001
2391 reflections	Δρmax = 0.24 e Å^−3
182 parameters	Δρmin = −0.17 e Å^−3
2 restraints	Absolute structure: Flack (1983); 812 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.05 (7)

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
S1	0.51970 (6)	0.85254 (6)	1.15002 (7)	0.04036 (15)
O1	0.04934 (15)	0.86575 (15)	1.08613 (18)	0.0329 (3)
O2	−0.13676 (15)	0.68768 (17)	0.67895 (19)	0.0363 (4)
O3	−0.25950 (17)	0.5626 (2)	0.4443 (2)	0.0533 (5)
N1	0.30161 (17)	0.78224 (18)	0.9008 (2)	0.0267 (4)
N2	0.12174 (17)	1.01991 (17)	0.9200 (2)	0.0271 (4)
H2	0.0982	1.0674	0.8237	0.033*
C1	0.3492 (2)	0.8850 (2)	1.0134 (2)	0.0263 (4)
C2	0.5246 (2)	0.6898 (2)	1.0447 (3)	0.0347 (5)
H2A	0.6031	0.6235	1.0716	0.042*
C3	0.4009 (2)	0.6681 (2)	0.9173 (3)	0.0272 (4)
C4	0.2678 (2)	1.0248 (2)	1.0305 (3)	0.0287 (4)
H4	0.2682	1.0290	1.1480	0.034*
C5	0.0214 (2)	0.9456 (2)	0.9595 (3)	0.0263 (4)
C6	−0.1287 (2)	0.9748 (2)	0.8473 (3)	0.0310 (5)
H6A	−0.1289	0.9950	0.7328	0.037*
H6B	−0.1633	1.0666	0.8868	0.037*
C7	−0.2317 (2)	0.8452 (2)	0.8399 (3)	0.0327 (5)
H7A	−0.1898	0.7791	0.9380	0.039*
H7B	−0.3199	0.8878	0.8479	0.039*
C8	−0.2675 (2)	0.7514 (3)	0.6841 (3)	0.0373 (5)
H8A	−0.3341	0.6703	0.6864	0.045*
H8B	−0.3119	0.8146	0.5841	0.045*
C9	−0.1486 (2)	0.5900 (2)	0.5522 (3)	0.0376 (5)
C10	−0.0128 (2)	0.5205 (2)	0.5669 (3)	0.0366 (5)
H10	−0.0114	0.4432	0.4903	0.044*
C11	0.1091 (2)	0.5608 (2)	0.6829 (3)	0.0303 (4)
H11	0.1073	0.6405	0.7565	0.036*
C12	0.2439 (2)	0.4907 (2)	0.7037 (3)	0.0328 (5)
H12	0.2430	0.4047	0.6370	0.039*
C13	0.3699 (2)	0.5361 (2)	0.8085 (3)	0.0317 (5)
H13	0.4484	0.4751	0.8124	0.038*
C14	0.3365 (2)	1.1680 (2)	0.9974 (3)	0.0379 (5)
H14A	0.2834	1.2556	1.0137	0.057*
H14B	0.3365	1.1671	0.8823	0.057*
H14C	0.4338	1.1737	1.0750	0.057*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0263 (3)	0.0413 (3)	0.0438 (3)	0.0004 (2)	−0.0008 (2)	−0.0080 (3)
O1	0.0383 (8)	0.0337 (8)	0.0250 (8)	−0.0008 (6)	0.0085 (7)	0.0017 (6)
O2	0.0263 (8)	0.0388 (8)	0.0397 (9)	0.0023 (6)	0.0057 (7)	−0.0088 (7)
O3	0.0357 (9)	0.0624 (11)	0.0535 (12)	−0.0078 (8)	0.0044 (8)	−0.0188 (9)
N1	0.0275 (8)	0.0237 (8)	0.0280 (9)	0.0004 (6)	0.0083 (7)	0.0011 (6)
N2	0.0306 (9)	0.0260 (8)	0.0242 (9)	0.0018 (7)	0.0084 (8)	0.0009 (7)
C1	0.0270 (10)	0.0274 (10)	0.0236 (11)	−0.0022 (8)	0.0071 (8)	0.0022 (8)
C2	0.0262 (11)	0.0330 (11)	0.0443 (14)	0.0037 (8)	0.0113 (10)	0.0011 (9)
C3	0.0262 (10)	0.0257 (9)	0.0326 (11)	0.0018 (7)	0.0139 (9)	0.0035 (8)
C4	0.0305 (10)	0.0299 (10)	0.0247 (11)	−0.0001 (8)	0.0081 (9)	−0.0022 (8)
C5	0.0314 (11)	0.0234 (9)	0.0251 (11)	0.0037 (8)	0.0107 (9)	−0.0029 (8)
C6	0.0311 (11)	0.0294 (10)	0.0336 (12)	0.0064 (8)	0.0125 (10)	0.0043 (9)
C7	0.0255 (10)	0.0351 (11)	0.0395 (13)	0.0061 (8)	0.0136 (10)	0.0057 (9)
C8	0.0224 (10)	0.0387 (12)	0.0472 (14)	0.0015 (8)	0.0071 (10)	−0.0002 (10)
C9	0.0362 (12)	0.0328 (11)	0.0408 (14)	−0.0078 (9)	0.0092 (11)	−0.0055 (10)
C10	0.0401 (12)	0.0308 (11)	0.0392 (12)	−0.0037 (9)	0.0140 (10)	−0.0085 (9)
C11	0.0352 (11)	0.0240 (9)	0.0337 (11)	−0.0003 (8)	0.0142 (10)	−0.0035 (8)
C12	0.0414 (12)	0.0237 (10)	0.0364 (12)	0.0014 (9)	0.0170 (10)	−0.0044 (9)
C13	0.0335 (11)	0.0254 (10)	0.0397 (13)	0.0059 (8)	0.0170 (10)	0.0009 (9)
C14	0.0369 (13)	0.0289 (11)	0.0475 (14)	−0.0050 (9)	0.0138 (11)	−0.0073 (10)

Geometric parameters (Å, º)

S1—C2	1.711 (2)	C6—H6A	0.9900
S1—C1	1.740 (2)	C6—H6B	0.9900
O1—C5	1.240 (2)	C7—C8	1.503 (3)
O2—C9	1.358 (3)	C7—H7A	0.9900
O2—C8	1.448 (3)	C7—H7B	0.9900
O3—C9	1.205 (3)	C8—H8A	0.9900
N1—C1	1.292 (3)	C8—H8B	0.9900
N1—C3	1.397 (2)	C9—C10	1.467 (3)
N2—C5	1.342 (2)	C10—C11	1.337 (3)
N2—C4	1.453 (2)	C10—H10	0.9500
N2—H2	0.8800	C11—C12	1.449 (3)
C1—C4	1.522 (3)	C11—H11	0.9500
C2—C3	1.359 (3)	C12—C13	1.342 (3)
C2—H2A	0.9500	C12—H12	0.9500
C3—C13	1.460 (3)	C13—H13	0.9500
C4—C14	1.520 (3)	C14—H14A	0.9800
C4—H4	1.0000	C14—H14B	0.9800
C5—C6	1.511 (3)	C14—H14C	0.9800
C6—C7	1.537 (3)
C2—S1—C1	89.30 (10)	C6—C7—H7A	108.7
C9—O2—C8	116.02 (17)	C8—C7—H7B	108.7
C1—N1—C3	111.45 (17)	C6—C7—H7B	108.7
C5—N2—C4	122.42 (16)	H7A—C7—H7B	107.6
C5—N2—H2	118.8	O2—C8—C7	107.20 (17)
C4—N2—H2	118.8	O2—C8—H8A	110.3
N1—C1—C4	124.82 (18)	C7—C8—H8A	110.3
N1—C1—S1	114.30 (15)	O2—C8—H8B	110.3
C4—C1—S1	120.88 (14)	C7—C8—H8B	110.3
C3—C2—S1	110.85 (15)	H8A—C8—H8B	108.5
C3—C2—H2A	124.6	O3—C9—O2	122.8 (2)
S1—C2—H2A	124.6	O3—C9—C10	125.2 (2)
C2—C3—N1	114.10 (17)	O2—C9—C10	111.95 (19)
C2—C3—C13	124.04 (18)	C11—C10—C9	123.1 (2)
N1—C3—C13	121.84 (18)	C11—C10—H10	118.4
N2—C4—C14	109.28 (17)	C9—C10—H10	118.4
N2—C4—C1	111.98 (15)	C10—C11—C12	124.28 (19)
C14—C4—C1	111.77 (17)	C10—C11—H11	117.9
N2—C4—H4	107.9	C12—C11—H11	117.9
C14—C4—H4	107.9	C13—C12—C11	126.01 (18)
C1—C4—H4	107.9	C13—C12—H12	117.0
O1—C5—N2	122.09 (18)	C11—C12—H12	117.0
O1—C5—C6	121.98 (18)	C12—C13—C3	127.78 (18)
N2—C5—C6	115.78 (17)	C12—C13—H13	116.1
C5—C6—C7	114.49 (16)	C3—C13—H13	116.1
C5—C6—H6A	108.6	C4—C14—H14A	109.5
C7—C6—H6A	108.6	C4—C14—H14B	109.5
C5—C6—H6B	108.6	H14A—C14—H14B	109.5
C7—C6—H6B	108.6	C4—C14—H14C	109.5
H6A—C6—H6B	107.6	H14A—C14—H14C	109.5
C8—C7—C6	114.05 (18)	H14B—C14—H14C	109.5
C8—C7—H7A	108.7
C3—N1—C1—C4	179.99 (18)	C4—N2—C5—C6	169.12 (16)
C3—N1—C1—S1	0.1 (2)	O1—C5—C6—C7	−31.0 (3)
C2—S1—C1—N1	0.31 (16)	N2—C5—C6—C7	153.50 (18)
C2—S1—C1—C4	−179.54 (17)	C5—C6—C7—C8	−102.6 (2)
C1—S1—C2—C3	−0.68 (17)	C9—O2—C8—C7	175.52 (18)
S1—C2—C3—N1	0.9 (2)	C6—C7—C8—O2	60.1 (2)
S1—C2—C3—C13	−177.35 (17)	C8—O2—C9—O3	3.8 (3)
C1—N1—C3—C2	−0.7 (2)	C8—O2—C9—C10	−174.46 (19)
C1—N1—C3—C13	177.62 (19)	O3—C9—C10—C11	175.9 (2)
C5—N2—C4—C14	−153.05 (18)	O2—C9—C10—C11	−6.0 (3)
C5—N2—C4—C1	82.6 (2)	C9—C10—C11—C12	177.9 (2)
N1—C1—C4—N2	8.2 (3)	C10—C11—C12—C13	173.8 (2)
S1—C1—C4—N2	−171.97 (14)	C11—C12—C13—C3	−3.3 (4)
N1—C1—C4—C14	−114.8 (2)	C2—C3—C13—C12	165.4 (2)
S1—C1—C4—C14	65.0 (2)	N1—C3—C13—C12	−12.7 (3)
C4—N2—C5—O1	−6.4 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O1^i	0.88	2.00	2.869 (2)	168

Symmetry code: (i) x, −y+2, z−1/2.