(1R,3S,4R,4aS,7R,7aS,10R,12aR)-3-Azido-4,7,10-trimethyl-1,10-epidioxy-per-hydropyrano[4,3-j][1,2]benzodiox-epine.

In the title compound, C(15)H(23)N(3)O(4), the six-membered pyran, cyclo-hexane and trioxane rings adopt chair, chair and boat conformations, respectively, while the seven-membered rings adopt distorted boat and very distorted chair conformations. In the crystal, adjacent mol-ecules are connected by weak C-H⋯N and C-H⋯O inter-actions.

Related literature

For general background to artemisinin, a sesquiterpene endoperoxide widely used to treat drug-resistant malaria, see: Liu et al. (1979 ▶). For the anti­cancer properties of the title compound, see: Efferth et al. (1996 ▶); Chadwick et al. (2009 ▶); Galal et al. (2009 ▶). For structural analyses of highly related compounds, see: Gul et al. (2009 ▶); Jasinskiet al. (2008 ▶).

Experimental

Crystal data

C15H23N3O4

M = 309.36

Orthorhombic,

a = 7.9938 (9) Å

b = 11.207 (1) Å

c = 17.984 (2) Å

V = 1611.1 (3) Å3

Z = 4

Mo Kα radiation

μ = 0.09 mm−1

T = 298 K

0.50 × 0.40 × 0.38 mm

Data collection

Bruker SMART CCD area-detector diffractometer

Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T min = 0.955, T max = 0.965

7585 measured reflections

1657 independent reflections

1130 reflections with I > 2σ(I)

R int = 0.043

Refinement

R[F 2 > 2σ(F 2)] = 0.040

wR(F 2) = 0.103

S = 1.09

1657 reflections

202 parameters

H-atom parameters constrained

Δρmax = 0.12 e Å−3

Δρmin = −0.16 e Å−3

Data collection: SMART (Bruker, 2003 ▶); cell refinement: SAINT (Bruker, 2003 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810024566/im2212sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810024566/im2212Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C15H23N3O4	F(000) = 664
Mr = 309.36	Dx = 1.275 Mg m−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 2309 reflections
a = 7.9938 (9) Å	θ = 2.3–21.4°
b = 11.207 (1) Å	µ = 0.09 mm−1
c = 17.984 (2) Å	T = 298 K
V = 1611.1 (3) Å3	Block, colorless
Z = 4	0.50 × 0.40 × 0.38 mm

Bruker SMART CCD area-detector diffractometer	1657 independent reflections
Radiation source: fine-focus sealed tube	1130 reflections with I > 2σ(I)
graphite	Rint = 0.043
phi and ω scans	θmax = 25.0°, θmin = 2.1°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −9→7
Tmin = 0.955, Tmax = 0.965	k = −13→13
7585 measured reflections	l = −16→21

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.040	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.103	H-atom parameters constrained
S = 1.09	w = 1/[σ2(Fo2) + (0.0312P)2 + 0.4488P] where P = (Fo2 + 2Fc2)/3
1657 reflections	(Δ/σ)max < 0.001
202 parameters	Δρmax = 0.12 e Å−3
0 restraints	Δρmin = −0.16 e Å−3

Experimental. We took dihydroartemisinin (mixture of 3R and 3S isomers of hydroxyl group) as the starting material in our experiment. During the course of synthesis, we got a mixture of two diastereomers with 3S and 3R and all other stereogenic centers are known and still in the configuration as they were in the starting compound. The mixture was separated by silica gel column chromatography and the title compound with 3S was crystallized under our conditions, while the other one (3R) was obtained as amorphous powder.

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.

	x	y	z	Uiso*/Ueq
N1	0.4489 (5)	0.4264 (3)	0.41235 (17)	0.0737 (10)
N2	0.3162 (6)	0.4810 (3)	0.41854 (19)	0.0756 (10)
N3	0.2016 (6)	0.5395 (4)	0.4253 (3)	0.1117 (15)
O1	0.3528 (3)	0.3297 (2)	0.30143 (11)	0.0583 (6)
O2	0.3573 (3)	0.3910 (2)	0.18223 (12)	0.0601 (7)
O3	0.4236 (3)	0.1895 (2)	0.17929 (14)	0.0726 (8)
O4	0.5935 (3)	0.2044 (2)	0.20749 (13)	0.0669 (7)
C1	0.4297 (5)	0.3114 (3)	0.37062 (18)	0.0656 (10)
H1	0.3554	0.2601	0.3999	0.079*
C2	0.5957 (5)	0.2491 (4)	0.3652 (2)	0.0738 (12)
H2	0.5712	0.1695	0.3454	0.089*
C3	0.7131 (5)	0.3075 (4)	0.3087 (2)	0.0670 (11)
H3	0.8021	0.2495	0.2989	0.080*
C4	0.6214 (4)	0.3259 (3)	0.23485 (17)	0.0528 (9)
C5	0.4547 (4)	0.3878 (3)	0.24650 (17)	0.0495 (9)
H5	0.4759	0.4699	0.2627	0.059*
C6	0.3823 (5)	0.2889 (4)	0.13467 (19)	0.0683 (11)
C7	0.5171 (5)	0.3170 (4)	0.0778 (2)	0.0789 (12)
H7A	0.5780	0.2444	0.0667	0.095*
H7B	0.4638	0.3435	0.0322	0.095*
C8	0.6406 (6)	0.4117 (4)	0.1028 (2)	0.0765 (12)
H8A	0.5809	0.4867	0.1075	0.092*
H8B	0.7234	0.4218	0.0639	0.092*
C9	0.7325 (5)	0.3881 (3)	0.1758 (2)	0.0653 (10)
H9	0.8227	0.3319	0.1640	0.078*
C10	0.8171 (5)	0.5007 (4)	0.2052 (2)	0.0798 (12)
H10	0.7293	0.5586	0.2172	0.096*
C11	0.9123 (5)	0.4740 (5)	0.2759 (3)	0.0973 (16)
H11A	0.9621	0.5470	0.2945	0.117*
H11B	1.0020	0.4184	0.2650	0.117*
C12	0.7998 (5)	0.4211 (4)	0.3354 (2)	0.0840 (13)
H12A	0.7159	0.4795	0.3493	0.101*
H12B	0.8661	0.4032	0.3791	0.101*
C13	0.6724 (7)	0.2282 (5)	0.4424 (2)	0.1150 (19)
H13A	0.6936	0.3037	0.4659	0.173*
H13B	0.7756	0.1851	0.4374	0.173*
H13C	0.5960	0.1828	0.4724	0.173*
C14	0.2153 (6)	0.2572 (5)	0.1011 (3)	0.1060 (17)
H14A	0.2293	0.1929	0.0665	0.159*
H14B	0.1704	0.3255	0.0758	0.159*
H14C	0.1398	0.2332	0.1398	0.159*
C15	0.9352 (6)	0.5587 (5)	0.1476 (3)	0.124 (2)
H15A	0.9829	0.6300	0.1683	0.186*
H15B	0.8730	0.5785	0.1036	0.186*
H15C	1.0229	0.5038	0.1351	0.186*

	U11	U22	U33	U12	U13	U23
N1	0.085 (2)	0.083 (2)	0.0530 (19)	−0.002 (2)	0.003 (2)	−0.0156 (19)
N2	0.094 (3)	0.079 (3)	0.055 (2)	−0.016 (2)	0.017 (2)	−0.015 (2)
N3	0.105 (3)	0.112 (3)	0.117 (4)	0.005 (3)	0.021 (3)	−0.037 (3)
O1	0.0652 (14)	0.0705 (16)	0.0393 (12)	−0.0044 (13)	0.0041 (11)	−0.0011 (12)
O2	0.0722 (15)	0.0672 (15)	0.0410 (13)	0.0191 (14)	−0.0084 (13)	−0.0062 (13)
O3	0.101 (2)	0.0608 (16)	0.0560 (14)	−0.0006 (16)	−0.0084 (15)	−0.0067 (15)
O4	0.0912 (19)	0.0523 (15)	0.0572 (14)	0.0182 (14)	0.0006 (14)	−0.0024 (13)
C1	0.095 (3)	0.065 (2)	0.0366 (17)	−0.013 (2)	0.0044 (19)	−0.0005 (19)
C2	0.107 (3)	0.070 (3)	0.044 (2)	0.014 (3)	−0.011 (2)	0.005 (2)
C3	0.068 (2)	0.071 (3)	0.062 (2)	0.019 (2)	−0.010 (2)	0.002 (2)
C4	0.061 (2)	0.051 (2)	0.0465 (18)	0.0126 (19)	0.0015 (17)	−0.0009 (17)
C5	0.058 (2)	0.054 (2)	0.0362 (16)	0.0069 (19)	−0.0015 (18)	−0.0046 (17)
C6	0.094 (3)	0.068 (3)	0.0431 (19)	0.013 (2)	−0.011 (2)	−0.008 (2)
C7	0.111 (3)	0.083 (3)	0.043 (2)	0.025 (3)	0.003 (2)	−0.002 (2)
C8	0.099 (3)	0.082 (3)	0.048 (2)	0.013 (3)	0.022 (2)	0.010 (2)
C9	0.065 (2)	0.068 (2)	0.063 (2)	0.017 (2)	0.016 (2)	−0.001 (2)
C10	0.067 (3)	0.083 (3)	0.090 (3)	−0.003 (2)	0.016 (2)	0.000 (3)
C11	0.063 (3)	0.118 (4)	0.111 (4)	−0.008 (3)	−0.001 (3)	−0.011 (3)
C12	0.076 (3)	0.103 (3)	0.073 (3)	0.007 (3)	−0.018 (2)	−0.006 (3)
C13	0.160 (5)	0.127 (4)	0.057 (3)	0.039 (4)	−0.024 (3)	0.018 (3)
C14	0.120 (4)	0.124 (4)	0.074 (3)	0.003 (4)	−0.035 (3)	−0.030 (3)
C15	0.108 (4)	0.121 (4)	0.143 (5)	−0.028 (4)	0.040 (4)	0.010 (4)

N1—N2	1.229 (5)	C7—H7A	0.9700
N1—C1	1.499 (5)	C7—H7B	0.9700
N2—N3	1.133 (5)	C8—C9	1.528 (5)
O1—C1	1.403 (4)	C8—H8A	0.9700
O1—C5	1.437 (4)	C8—H8B	0.9700
O2—C5	1.394 (4)	C9—C10	1.526 (5)
O2—C6	1.442 (4)	C9—H9	0.9800
O3—C6	1.412 (4)	C10—C11	1.511 (6)
O3—O4	1.459 (3)	C10—C15	1.545 (6)
O4—C4	1.464 (4)	C10—H10	0.9800
C1—C2	1.503 (6)	C11—C12	1.518 (6)
C1—H1	0.9800	C11—H11A	0.9700
C2—C3	1.530 (5)	C11—H11B	0.9700
C2—C13	1.536 (5)	C12—H12A	0.9700
C2—H2	0.9800	C12—H12B	0.9700
C3—C12	1.527 (5)	C13—H13A	0.9600
C3—C4	1.531 (4)	C13—H13B	0.9600
C3—H3	0.9800	C13—H13C	0.9600
C4—C5	1.517 (5)	C14—H14A	0.9600
C4—C9	1.550 (5)	C14—H14B	0.9600
C5—H5	0.9800	C14—H14C	0.9600
C6—C14	1.507 (5)	C15—H15A	0.9600
C6—C7	1.518 (5)	C15—H15B	0.9600
C7—C8	1.518 (6)	C15—H15C	0.9600
N2—N1—C1	112.6 (3)	C7—C8—C9	116.5 (3)
N3—N2—N1	174.3 (4)	C7—C8—H8A	108.2
C1—O1—C5	115.3 (3)	C9—C8—H8A	108.2
C5—O2—C6	113.2 (3)	C7—C8—H8B	108.2
C6—O3—O4	108.9 (3)	C9—C8—H8B	108.2
O3—O4—C4	111.4 (2)	H8A—C8—H8B	107.3
O1—C1—N1	111.3 (3)	C10—C9—C8	111.6 (3)
O1—C1—C2	113.4 (3)	C10—C9—C4	112.8 (3)
N1—C1—C2	110.0 (3)	C8—C9—C4	113.0 (3)
O1—C1—H1	107.3	C10—C9—H9	106.3
N1—C1—H1	107.3	C8—C9—H9	106.3
C2—C1—H1	107.3	C4—C9—H9	106.3
C1—C2—C3	112.7 (3)	C11—C10—C9	110.6 (4)
C1—C2—C13	111.4 (3)	C11—C10—C15	109.9 (4)
C3—C2—C13	114.9 (4)	C9—C10—C15	112.7 (4)
C1—C2—H2	105.7	C11—C10—H10	107.9
C3—C2—H2	105.7	C9—C10—H10	107.9
C13—C2—H2	105.7	C15—C10—H10	107.9
C12—C3—C2	115.3 (3)	C10—C11—C12	111.8 (3)
C12—C3—C4	112.2 (3)	C10—C11—H11A	109.3
C2—C3—C4	109.9 (3)	C12—C11—H11A	109.3
C12—C3—H3	106.3	C10—C11—H11B	109.3
C2—C3—H3	106.3	C12—C11—H11B	109.3
C4—C3—H3	106.3	H11A—C11—H11B	107.9
O4—C4—C5	109.7 (3)	C11—C12—C3	111.9 (4)
O4—C4—C3	103.9 (3)	C11—C12—H12A	109.2
C5—C4—C3	111.2 (3)	C3—C12—H12A	109.2
O4—C4—C9	106.0 (3)	C11—C12—H12B	109.2
C5—C4—C9	113.1 (3)	C3—C12—H12B	109.2
C3—C4—C9	112.4 (3)	H12A—C12—H12B	107.9
O2—C5—O1	105.4 (3)	C2—C13—H13A	109.5
O2—C5—C4	112.8 (3)	C2—C13—H13B	109.5
O1—C5—C4	112.7 (3)	H13A—C13—H13B	109.5
O2—C5—H5	108.6	C2—C13—H13C	109.5
O1—C5—H5	108.6	H13A—C13—H13C	109.5
C4—C5—H5	108.6	H13B—C13—H13C	109.5
O3—C6—O2	108.7 (3)	C6—C14—H14A	109.5
O3—C6—C14	104.4 (4)	C6—C14—H14B	109.5
O2—C6—C14	107.5 (3)	H14A—C14—H14B	109.5
O3—C6—C7	112.4 (3)	C6—C14—H14C	109.5
O2—C6—C7	109.5 (3)	H14A—C14—H14C	109.5
C14—C6—C7	114.1 (3)	H14B—C14—H14C	109.5
C8—C7—C6	114.0 (3)	C10—C15—H15A	109.5
C8—C7—H7A	108.7	C10—C15—H15B	109.5
C6—C7—H7A	108.7	H15A—C15—H15B	109.5
C8—C7—H7B	108.7	C10—C15—H15C	109.5
C6—C7—H7B	108.7	H15A—C15—H15C	109.5
H7A—C7—H7B	107.6	H15B—C15—H15C	109.5
C1—N1—N2—N3	−159 (4)	O4—C4—C5—O1	62.1 (3)
C6—O3—O4—C4	44.7 (3)	C3—C4—C5—O1	−52.3 (4)
C5—O1—C1—N1	72.1 (4)	C9—C4—C5—O1	−179.9 (3)
C5—O1—C1—C2	−52.6 (4)	O4—O3—C6—O2	−72.3 (3)
N2—N1—C1—O1	53.7 (4)	O4—O3—C6—C14	173.2 (3)
N2—N1—C1—C2	−179.8 (3)	O4—O3—C6—C7	49.0 (4)
O1—C1—C2—C3	50.7 (4)	C5—O2—C6—O3	30.7 (4)
N1—C1—C2—C3	−74.6 (4)	C5—O2—C6—C14	143.2 (3)
O1—C1—C2—C13	−178.5 (4)	C5—O2—C6—C7	−92.4 (3)
N1—C1—C2—C13	56.2 (5)	O3—C6—C7—C8	−95.2 (4)
C1—C2—C3—C12	78.1 (4)	O2—C6—C7—C8	25.7 (4)
C13—C2—C3—C12	−50.9 (5)	C14—C6—C7—C8	146.2 (4)
C1—C2—C3—C4	−49.8 (4)	C6—C7—C8—C9	56.2 (5)
C13—C2—C3—C4	−178.8 (3)	C7—C8—C9—C10	−165.3 (3)
O3—O4—C4—C5	16.4 (3)	C7—C8—C9—C4	−36.8 (5)
O3—O4—C4—C3	135.4 (3)	O4—C4—C9—C10	−162.7 (3)
O3—O4—C4—C9	−106.0 (3)	C5—C4—C9—C10	77.1 (4)
C12—C3—C4—O4	162.9 (3)	C3—C4—C9—C10	−49.8 (4)
C2—C3—C4—O4	−67.5 (4)	O4—C4—C9—C8	69.6 (4)
C12—C3—C4—C5	−79.1 (4)	C5—C4—C9—C8	−50.7 (4)
C2—C3—C4—C5	50.5 (4)	C3—C4—C9—C8	−177.6 (3)
C12—C3—C4—C9	48.8 (4)	C8—C9—C10—C11	−177.9 (3)
C2—C3—C4—C9	178.4 (3)	C4—C9—C10—C11	53.5 (4)
C6—O2—C5—O1	−91.5 (3)	C8—C9—C10—C15	−54.6 (5)
C6—O2—C5—C4	31.9 (4)	C4—C9—C10—C15	176.9 (3)
C1—O1—C5—O2	177.1 (3)	C9—C10—C11—C12	−57.2 (5)
C1—O1—C5—C4	53.7 (4)	C15—C10—C11—C12	177.8 (4)
O4—C4—C5—O2	−57.1 (4)	C10—C11—C12—C3	57.2 (5)
C3—C4—C5—O2	−171.5 (3)	C2—C3—C12—C11	−179.4 (3)
C9—C4—C5—O2	61.0 (4)	C4—C3—C12—C11	−52.6 (4)

D—H···A	D—H	H···A	D···A	D—H···A
C7—H7B···N3i	0.97	2.68	3.628 (6)	167
C10—H10···O3ii	0.98	2.67	3.535 (5)	148
C12—H12A···O3ii	0.97	2.65	3.508 (5)	147

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C7—H7B⋯N3i	0.97	2.68	3.628 (6)	167
C10—H10⋯O3ii	0.98	2.67	3.535 (5)	148
C12—H12A⋯O3ii	0.97	2.65	3.508 (5)	147

Symmetry codes: (i) ; (ii) .