Crystal structure of 5-hydroxy-4,6,9,10-tetramethyl-1-oxo-6-vinyldecahydro-3a,9-propanocyclopenta[8]annulen-8-yl 2-((2-methyl-1-(3-methylbenzamido)propan-2-yl)thio)acetate, C34H49NO5S

Guirong Wang; Fengwu Zhao

doi:10.1515/ncrs-2016-0175

Artikel Open Access

Crystal structure of 5-hydroxy-4,6,9,10-tetramethyl-1-oxo-6-vinyldecahydro-3a,9-propanocyclopenta[8]annulen-8-yl 2-((2-methyl-1-(3-methylbenzamido)propan-2-yl)thio)acetate, C₃₄H₄₉NO₅S

Guirong Wang und Fengwu Zhao

Veröffentlicht/Copyright: 17. Dezember 2016

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Aus der Zeitschrift Zeitschrift für Kristallographie - New Crystal Structures Band 232 Heft 2

Abstract

C₃₄H₄₉NO₅S, monoclinic, P2₁ (no. 4), a = 14.4605(4) Å, b = 9.9703(4) Å, c = 22.7599(7) Å, β = 94.799(3) Å; V = 3269.90 Å³, Z = 4, R_gt(F) = 0.0638, wR_ref(F²) = 0.1482, T = 293 K.

CCDC no.:: 1482589

A part of the title crystal structure is shown in the figure. Tables 1 and 2 contain details on crystal structure and measurement conditions and a list of the atoms including atomic coordinates and displacement parameters.

Table 1

Data collection and handling.

Crystal:	Colourless block
Size:	0.35 × 0.33 × 0.31 mm
Wavelength:	Mo Kα radiation (0.71073 Å)
μ:	1.4 cm⁻¹
Diffractometer, scan mode:	SuperNova, ω-scans
2θ_max, completeness:	52°, >99%
N(hkl)_measured, N(hkl)_unique, R_int:	13678, 9926, 0.039
Criterion for I_obs, N(hkl)_gt:	I_obs > 2 σ(I_obs), 5866
N(param)_refined:	755
Programs:	CrysAlis^PRO [7], SHELX [8], OLEX2 [9]

Table 2

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²).

Atom	x	y	z	U_iso*/U_eq
S1	0.49527(10)	0.2562(2)	0.26776(6)	0.0552(4)
O1	0.3369(4)	0.0282(6)	0.6105(2)	0.106(2)
O2	0.1137(3)	0.5768(5)	0.53492(18)	0.0594(12)
H2	0.1223	0.6037	0.5690	0.089*
O3	0.4257(2)	0.3043(4)	0.42586(16)	0.0464(11)
O4	0.3510(2)	0.3602(5)	0.33942(17)	0.0654(14)
O5	0.8192(3)	0.1258(6)	0.34510(19)	0.0781(16)
N1	0.7371(3)	0.0472(6)	0.2635(2)	0.0567(15)
H1	0.7390	0.0053	0.2306	0.068*
C1	0.3410(3)	0.3181(6)	0.4578(2)	0.0387(14)
H1A	0.2862	0.3128	0.4295	0.046*
C2	0.3433(3)	0.1945(6)	0.4992(2)	0.0418(15)
C3	0.2767(3)	0.2158(6)	0.5483(2)	0.0476(16)
H3	0.2942	0.3015	0.5671	0.057*
C4	0.1711(4)	0.2250(7)	0.5290(3)	0.0563(18)
C5	0.1408(3)	0.3533(6)	0.4950(3)	0.0494(16)
H5	0.1647	0.3456	0.4561	0.059*
C6	0.1843(4)	0.4814(6)	0.5236(3)	0.0468(16)
H6	0.2154	0.4555	0.5618	0.056*
C7	0.2584(4)	0.5467(6)	0.4874(3)	0.0452(15)
C8	0.3459(4)	0.4578(6)	0.4861(3)	0.0473(16)
H8A	0.3912	0.5090	0.4663	0.057*
H8B	0.3711	0.4462	0.5266	0.057*
C9	0.3115(4)	0.0660(7)	0.4656(3)	0.0558(17)
H9	0.3175	−0.0066	0.4947	0.067*
C10	0.2079(4)	0.0720(7)	0.4442(3)	0.074(2)
H10A	0.1982	0.1431	0.4153	0.089*
H10B	0.1900	−0.0119	0.4250	0.089*
C11	0.1461(4)	0.0968(8)	0.4940(4)	0.078(2)
H11A	0.1508	0.0208	0.5207	0.093*
H11B	0.0821	0.1029	0.4776	0.093*
C12	0.2786(5)	0.1127(9)	0.5972(3)	0.080(2)
C13	0.1905(5)	0.1248(10)	0.6280(4)	0.121(4)
H13A	0.2034	0.1621	0.6671	0.145*
H13B	0.1615	0.0377	0.6313	0.145*
C14	0.1281(4)	0.2181(9)	0.5895(3)	0.089(3)
H14A	0.1265	0.3065	0.6072	0.106*
H14B	0.0654	0.1831	0.5845	0.106*
C15	0.3673(5)	0.0212(8)	0.4149(3)	0.086(2)
H15A	0.3489	0.0731	0.3803	0.129*
H15B	0.3558	−0.0721	0.4068	0.129*
H15C	0.4322	0.0345	0.4257	0.129*
C16	0.4425(3)	0.1779(7)	0.5280(3)	0.062(2)
H16A	0.4462	0.0975	0.5514	0.092*
H16B	0.4582	0.2538	0.5528	0.092*
H16C	0.4851	0.1719	0.4980	0.092*
C17	0.0338(3)	0.3624(8)	0.4842(3)	0.075(2)
H17A	0.0105	0.2828	0.4643	0.113*
H17B	0.0174	0.4394	0.4603	0.113*
H17C	0.0072	0.3705	0.5213	0.113*
C18	0.2186(4)	0.5749(8)	0.4241(3)	0.067(2)
H18	0.2404	0.5196	0.3954	0.080*
C19	0.1603(6)	0.6629(10)	0.4054(4)	0.115(3)
H19A	0.1357	0.7216	0.4318	0.138*
H19B	0.1421	0.6688	0.3653	0.138*
C20	0.2904(4)	0.6786(7)	0.5173(3)	0.072(2)
H20A	0.2392	0.7402	0.5162	0.108*
H20B	0.3396	0.7168	0.4969	0.108*
H20C	0.3123	0.6613	0.5576	0.108*
C21	0.4201(4)	0.3255(6)	0.3679(3)	0.0475(16)
C22	0.5128(3)	0.2954(8)	0.3445(2)	0.0581(19)
H22A	0.5420	0.2203	0.3658	0.070*
H22B	0.5534	0.3727	0.3502	0.070*
C23	0.6141(4)	0.2230(6)	0.2483(2)	0.0462(15)
C24	0.6027(4)	0.2023(8)	0.1816(3)	0.080(2)
H24A	0.5617	0.1281	0.1725	0.120*
H24B	0.6621	0.1838	0.1675	0.120*
H24C	0.5772	0.2819	0.1630	0.120*
C25	0.6782(4)	0.3400(7)	0.2633(3)	0.071(2)
H25A	0.6507	0.4208	0.2468	0.107*
H25B	0.7366	0.3248	0.2472	0.107*
H25C	0.6879	0.3490	0.3054	0.107*
C26	0.6478(4)	0.0948(7)	0.2798(3)	0.0540(17)
H26A	0.6521	0.1106	0.3220	0.065*
H26B	0.6019	0.0249	0.2712	0.065*
C27	0.8172(4)	0.0658(7)	0.2974(3)	0.0553(17)
C28	0.9049(4)	0.0086(7)	0.2754(3)	0.0535(17)
C29	0.9108(4)	−0.0249(7)	0.2177(3)	0.0589(19)
H29	0.8586	−0.0169	0.1911	0.071*
C30	0.9939(4)	−0.0712(7)	0.1978(3)	0.0588(18)
C31	1.0687(4)	−0.0828(8)	0.2383(3)	0.067(2)
H31	1.1248	−0.1138	0.2263	0.080*
C32	1.0629(5)	−0.0500(9)	0.2958(4)	0.080(2)
H32	1.1151	−0.0598	0.3222	0.096*
C33	0.9821(4)	−0.0026(8)	0.3161(3)	0.068(2)
H33	0.9791	0.0211	0.3554	0.082*
C34	1.0008(5)	−0.1042(9)	0.1339(3)	0.088(3)
H34A	0.9907	−0.0244	0.1106	0.132*
H34B	0.9546	−0.1699	0.1215	0.132*
H34C	1.0613	−0.1395	0.1287	0.132*
S2	0.45272(10)	0.2528(2)	0.76987(7)	0.0571(5)
O6	0.1262(3)	0.6114(5)	1.06007(18)	0.0636(13)
H6A	0.1326	0.6306	1.0952	0.095*
O7	0.3711(3)	0.0703(6)	1.1284(2)	0.0930(18)
O8	0.4093(2)	0.3295(4)	0.92966(16)	0.0473(10)
O9	0.3170(3)	0.3737(5)	0.84763(17)	0.0641(14)
O10	0.7918(3)	0.1680(5)	0.82648(18)	0.0594(12)
N2	0.6988(3)	0.0562(6)	0.7589(2)	0.0567(14)
H2A	0.6962	0.0050	0.7284	0.068*
C35	0.3342(3)	0.3444(6)	0.9693(2)	0.0434(15)
H35	0.2739	0.3365	0.9465	0.052*
C36	0.3476(4)	0.2258(6)	1.0134(2)	0.0468(15)
C37	0.2950(3)	0.2505(7)	1.0683(2)	0.0429(14)
H37	0.3160	0.3380	1.0839	0.051*
C38	0.1878(3)	0.2576(7)	1.0606(2)	0.0452(14)
C39	0.1465(3)	0.3800(6)	1.0266(3)	0.0462(16)
H39	0.1587	0.3677	0.9852	0.055*
C40	0.1940(4)	0.5126(6)	1.0473(3)	0.0488(16)
H40	0.2322	0.4940	1.0840	0.059*
C41	0.2584(4)	0.5752(6)	1.0029(3)	0.0476(15)
C42	0.3451(4)	0.4849(6)	0.9952(3)	0.0461(15)
H42A	0.3852	0.5344	0.9708	0.055*
H42B	0.3785	0.4760	1.0338	0.055*
C43	0.4520(4)	0.2132(8)	1.0334(3)	0.073(2)
H43A	0.4622	0.1340	1.0570	0.109*
H43B	0.4717	0.2906	1.0561	0.109*
H43C	0.4868	0.2071	0.9993	0.109*
C44	0.3095(4)	0.0911(7)	0.9854(3)	0.0570(17)
H44	0.3241	0.0210	1.0149	0.068*
C45	0.2025(4)	0.0957(8)	0.9747(3)	0.070(2)
H45A	0.1851	0.1642	0.9456	0.084*
H45B	0.1803	0.0102	0.9589	0.084*
C46	0.1560(4)	0.1253(7)	1.0303(3)	0.0632(19)
H46A	0.1687	0.0521	1.0578	0.076*
H46B	0.0895	0.1290	1.0207	0.076*
C47	0.3105(5)	0.1518(8)	1.1194(3)	0.067(2)
C48	0.2332(5)	0.1703(8)	1.1595(3)	0.087(3)
H48A	0.2560	0.2154	1.1956	0.104*
H48B	0.2075	0.0842	1.1695	0.104*
C49	0.1605(4)	0.2551(8)	1.1250(3)	0.0656(18)
H49A	0.1600	0.3453	1.1410	0.079*
H49B	0.0994	0.2161	1.1268	0.079*
C50	0.3516(5)	0.0452(7)	0.9289(3)	0.084(2)
H50A	0.3276	0.0997	0.8964	0.126*
H50B	0.3356	−0.0469	0.9211	0.126*
H50C	0.4179	0.0541	0.9340	0.126*
C51	0.0401(3)	0.3872(8)	1.0283(3)	0.072(2)
H51A	0.0253	0.4029	1.0681	0.109*
H51B	0.0128	0.3041	1.0144	0.109*
H51C	0.0159	0.4592	1.0035	0.109*
C52	0.2073(4)	0.5956(7)	0.9425(3)	0.0622(18)
H52	0.2107	0.5241	0.9166	0.075*
C53	0.1612(5)	0.6945(8)	0.9225(4)	0.096(3)
H53A	0.1548	0.7697	0.9460	0.115*
H53B	0.1334	0.6925	0.8841	0.115*
C54	0.2960(4)	0.7079(7)	1.0284(3)	0.071(2)
H54A	0.3269	0.6927	1.0668	0.107*
H54B	0.2456	0.7695	1.0314	0.107*
H54C	0.3392	0.7449	1.0030	0.107*
C55	0.3906(4)	0.3456(7)	0.8719(3)	0.0483(15)
C56	0.4790(4)	0.3215(8)	0.8425(2)	0.0607(19)
H56A	0.5184	0.2597	0.8661	0.073*
H56B	0.5124	0.4053	0.8398	0.073*
C58	0.5693(4)	0.2238(6)	0.7447(2)	0.0489(16)
C59	0.5474(4)	0.1856(9)	0.6792(3)	0.080(2)
H59A	0.5055	0.1108	0.6764	0.120*
H59B	0.6038	0.1617	0.6624	0.120*
H59C	0.5192	0.2606	0.6581	0.120*
C60	0.6293(4)	0.3482(7)	0.7502(3)	0.0652(19)
H60A	0.5963	0.4222	0.7314	0.098*
H60B	0.6855	0.3329	0.7316	0.098*
H60C	0.6441	0.3684	0.7912	0.098*
C61	0.6122(4)	0.1046(7)	0.7799(3)	0.0539(17)
H61A	0.6236	0.1310	0.8209	0.065*
H61B	0.5677	0.0316	0.7781	0.065*
C62	0.7826(4)	0.0884(7)	0.7854(3)	0.0475(16)
C63	0.8665(4)	0.0194(7)	0.7638(3)	0.0502(16)
C64	0.9525(4)	0.0605(8)	0.7872(3)	0.065(2)
H64	0.9565	0.1290	0.8150	0.078*
C65	1.0331(5)	0.0030(9)	0.7705(3)	0.075(2)
C66	1.0267(5)	−0.0990(9)	0.7311(4)	0.087(3)
H66	1.0806	−0.1398	0.7204	0.104*
C67	0.9427(5)	−0.1431(9)	0.7069(3)	0.090(3)
H67	0.9397	−0.2121	0.6792	0.108*
C68	0.8620(5)	−0.0849(8)	0.7235(3)	0.074(2)
H68	0.8047	−0.1160	0.7075	0.089*
C69	1.1259(4)	0.0544(12)	0.7977(4)	0.131(4)
H69A	1.1335	0.0296	0.8386	0.196*
H69B	1.1278	0.1504	0.7943	0.196*
H69C	1.1751	0.0159	0.7774	0.196*

Source of material

3-Methylbenzoic acid (0.45 g, 3.3 mmol) was added dropwise to a solution of 14-O-[(1-amino-2-methylpropane-2-yl)thioacetyl]mutilin (1.39 g, 3.0 mmol) and triethylamine (0.81 g, 8.0 mmol) in dichloromethane (60 mL) and was stirred at room temperature for 4.5 h. Then the reaction mixture was washed with saturated aqueous NH₄Cl and water and dried with anhydrous Na₂SO₄ overnight. The solvent was evaporated in vacuum and the residue was chromatographed on silica gel (petroleum ether:ethyl acetate 2:1 v/v) to afford a pure product (1.29 g, yield: 74%; m.p. 67–69 ^oC). Single crystals were obtained by slow evaporation from a dichloromethane solution at room temperature.

Experimental details

Carbon-bound H atoms were placed in calculated positions and were included in the refinement using the riding model approximation, with U_iso(H) set to 1.2U_eq(C). The H atoms of the methyl group were allowed to rotate with a fixed angle around the C—C bond to best fit the experimental electron density, with U_iso(H) set to 1.5U_eq(C). The H atoms of the hydroxyl groups were allowed to rotate with a fixed angle around the C—O bond to best fit the experimental electron density (HFIX 147 in the SHELXL program [8]), with U_iso(H) set to 1.5U_eq(O).

Discussion

Pleuromutilins are important diterpenes which exhibit high activities against drug-resistant Grampositive bacteria and mycoplasmas in vitro and in vivo [1]. Pleuromutilins selectively inhibit bacterial protein synthesis through interaction with prokaryotic ribosomes at the acceptor and donor site (A- and P site, respectively) [2]. This unique antibacterial mechanism makes pleuromutilins display high antibacterial activities with no target-specific cross-resistance to other antibiotics [3]. The modification of pleuromutilin has led to three drugs: tiamulin [4], valnemulin [5], and retapamulin [6]. We have been engaged in the design and preparation of the pleuromutilin derivatives with potential biological activities recently. Herein we report the X-ray crystal structure of the title compound which showed potential antibacterial activity.

The crystal structure of the title compound consists of C₃₄H₄₉NO₅S molecules possessing a 5-6-8 tricyclic carbon skeleton and a benzene ring, in which all bond lengths are in normal ranges. The synthesized side chain of pleuromutilin exhibits zig-zag conformation. Six intramolecular H-bonds are formed among the molecules. Also, there are three intermolecular H-bonds (O1—H1⋯O9, O2—H2⋯O5, N2—H2A⋯O4, and O6—H6A⋯O10 linking the molecules to chains along the a direction.

Acknowledgements

This work was supported by grants from Lanzhou Talent Innovation and Entrepreneurship Project (2015-RC-21).

References

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Received: 2016-5-30

Accepted: 2016-11-2

Published Online: 2016-12-17

Published in Print: 2017-3-1

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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Crystal structure of 5-hydroxy-4,6,9,10-tetramethyl-1-oxo-6-vinyldecahydro-3a,9-propanocyclopenta[8]annulen-8-yl 2-((2-methyl-1-(3-methylbenzamido)propan-2-yl)thio)acetate, C34H49NO5S

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Abstract

Source of material

Experimental details

Discussion

Acknowledgements

References

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Crystal structure of 5-hydroxy-4,6,9,10-tetramethyl-1-oxo-6-vinyldecahydro-3a,9-propanocyclopenta[8]annulen-8-yl 2-((2-methyl-1-(3-methylbenzamido)propan-2-yl)thio)acetate, C₃₄H₄₉NO₅S