Crystal Structure of 5-Hydroxy-4, 6, 9, 10-Tetramethyl-1-Oxo-6

Z. Kristallogr. NCS 2017; 232(2): 173–176

Open Access

Guirong Wang and Fengwu Zhao* Crystal structure of 5-hydroxy-4,6,9,10-tetramethyl-1-oxo-6-vinyldecahydro-3a,9-propano- cyclopenta[8]annulen-8-yl 2-((2-methyl-1-(3- methylbenzamido)propan-2-yl)thio)acetate, C34H49NO5S

DOI 10.1515/ncrs-2016-0175 Table 1: Data collection and handling. Received May 30, 2016; accepted November 2, 2016; available online December 17, 2016 Crystal: Colourless block Size: 0.35 × 0.33 × 0.31 mm Abstract Wavelength: Mo Kα radiation (0.71073 Å) µ: 1.4 cm−1 C34H49NO5S, monoclinic, P21 (no. 4), a = 14.4605(4) Å, Diractometer, scan mode: SuperNova, ω-scans b = 9.9703(4) Å, c = 22.7599(7) Å, β = 94.799(3) Å; V = θ > 3 2 2 max, completeness: 52°, 99% 3269.90 Å , Z = 4, Rgt(F) = 0.0638, wRref(F ) = 0.1482, N(hkl)measured, N(hkl)unique, Rint: 13678, 9926, 0.039 T = 293 K. Criterion for Iobs, N(hkl)gt: Iobs > 2 σ(Iobs), 5866 N(param) : 755 CCDC no.: 1482589 rened Programs: CrysAlisPRO [7], SHELX [8], OLEX2 A part of the title crystal structure is shown in the gure. [9] Tables 1 and 2 contain details on crystal structure and mea- surement conditions and a list of the atoms including atomic Source of material coordinates and displacement parameters. 3-Methylbenzoic acid (0.45 g, 3.3 mmol) was added drop- wise to a solution of 14-O-[(1-amino-2-methylpropane-2- *Corresponding author: Fengwu Zhao, Lanzhou Vocational Techni- yl)thioacetyl]mutilin (1.39 g, 3.0 mmol) and triethylamine cal College, No. 37, LiushaGonglu, Anning District, Lanzhou 730070, Gansu Province, P. R. China, e-mail: [email protected] (0.81 g, 8.0 mmol) in dichloromethane (60 mL) and was Guirong Wang: Gansu Agricultural University, No.1 Yingmen Village, stirred at room temperature for 4.5 h. Then the reaction Anning District, Lanzhou 730070, Gansu Province, P. R. China mixture was washed with saturated aqueous NH4Cl and

Table 2: Fractional atomic coordinates and isotropic or equivalent Table 2 (continued) isotropic displacement parameters (Å2).

Atom x y z Uiso*/Ueq Atom x y z Uiso*/Ueq C20 0.2904(4) 0.6786(7) 0.5173(3) 0.072(2) S1 0.49527(10) 0.2562(2) 0.26776(6) 0.0552(4) H20A 0.2392 0.7402 0.5162 0.108* O1 0.3369(4) 0.0282(6) 0.6105(2) 0.106(2) H20B 0.3396 0.7168 0.4969 0.108* O2 0.1137(3) 0.5768(5) 0.53492(18) 0.0594(12) H20C 0.3123 0.6613 0.5576 0.108* H2 0.1223 0.6037 0.5690 0.089* C21 0.4201(4) 0.3255(6) 0.3679(3) 0.0475(16) O3 0.4257(2) 0.3043(4) 0.42586(16) 0.0464(11) C22 0.5128(3) 0.2954(8) 0.3445(2) 0.0581(19) O4 0.3510(2) 0.3602(5) 0.33942(17) 0.0654(14) H22A 0.5420 0.2203 0.3658 0.070* O5 0.8192(3) 0.1258(6) 0.34510(19) 0.0781(16) H22B 0.5534 0.3727 0.3502 0.070* N1 0.7371(3) 0.0472(6) 0.2635(2) 0.0567(15) C23 0.6141(4) 0.2230(6) 0.2483(2) 0.0462(15) H1 0.7390 0.0053 0.2306 0.068* C24 0.6027(4) 0.2023(8) 0.1816(3) 0.080(2) C1 0.3410(3) 0.3181(6) 0.4578(2) 0.0387(14) H24A 0.5617 0.1281 0.1725 0.120* H1A 0.2862 0.3128 0.4295 0.046* H24B 0.6621 0.1838 0.1675 0.120* C2 0.3433(3) 0.1945(6) 0.4992(2) 0.0418(15) H24C 0.5772 0.2819 0.1630 0.120* C3 0.2767(3) 0.2158(6) 0.5483(2) 0.0476(16) C25 0.6782(4) 0.3400(7) 0.2633(3) 0.071(2) H3 0.2942 0.3015 0.5671 0.057* H25A 0.6507 0.4208 0.2468 0.107* C4 0.1711(4) 0.2250(7) 0.5290(3) 0.0563(18) H25B 0.7366 0.3248 0.2472 0.107* C5 0.1408(3) 0.3533(6) 0.4950(3) 0.0494(16) H25C 0.6879 0.3490 0.3054 0.107* H5 0.1647 0.3456 0.4561 0.059* C26 0.6478(4) 0.0948(7) 0.2798(3) 0.0540(17) C6 0.1843(4) 0.4814(6) 0.5236(3) 0.0468(16) H26A 0.6521 0.1106 0.3220 0.065* H6 0.2154 0.4555 0.5618 0.056* H26B 0.6019 0.0249 0.2712 0.065* C7 0.2584(4) 0.5467(6) 0.4874(3) 0.0452(15) C27 0.8172(4) 0.0658(7) 0.2974(3) 0.0553(17) C8 0.3459(4) 0.4578(6) 0.4861(3) 0.0473(16) C28 0.9049(4) 0.0086(7) 0.2754(3) 0.0535(17) H8A 0.3912 0.5090 0.4663 0.057* C29 0.9108(4) −0.0249(7) 0.2177(3) 0.0589(19) H8B 0.3711 0.4462 0.5266 0.057* H29 0.8586 −0.0169 0.1911 0.071* C9 0.3115(4) 0.0660(7) 0.4656(3) 0.0558(17) C30 0.9939(4) −0.0712(7) 0.1978(3) 0.0588(18) H9 0.3175 −0.0066 0.4947 0.067* C31 1.0687(4) −0.0828(8) 0.2383(3) 0.067(2) C10 0.2079(4) 0.0720(7) 0.4442(3) 0.074(2) H31 1.1248 −0.1138 0.2263 0.080* H10A 0.1982 0.1431 0.4153 0.089* C32 1.0629(5) −0.0500(9) 0.2958(4) 0.080(2) H10B 0.1900 −0.0119 0.4250 0.089* H32 1.1151 −0.0598 0.3222 0.096* C11 0.1461(4) 0.0968(8) 0.4940(4) 0.078(2) C33 0.9821(4) −0.0026(8) 0.3161(3) 0.068(2) H11A 0.1508 0.0208 0.5207 0.093* H33 0.9791 0.0211 0.3554 0.082* H11B 0.0821 0.1029 0.4776 0.093* C34 1.0008(5) −0.1042(9) 0.1339(3) 0.088(3) C12 0.2786(5) 0.1127(9) 0.5972(3) 0.080(2) H34A 0.9907 −0.0244 0.1106 0.132* C13 0.1905(5) 0.1248(10) 0.6280(4) 0.121(4) H34B 0.9546 −0.1699 0.1215 0.132* H13A 0.2034 0.1621 0.6671 0.145* H34C 1.0613 −0.1395 0.1287 0.132* H13B 0.1615 0.0377 0.6313 0.145* S2 0.45272(10) 0.2528(2) 0.76987(7) 0.0571(5) C14 0.1281(4) 0.2181(9) 0.5895(3) 0.089(3) O6 0.1262(3) 0.6114(5) 1.06007(18) 0.0636(13) H14A 0.1265 0.3065 0.6072 0.106* H6A 0.1326 0.6306 1.0952 0.095* H14B 0.0654 0.1831 0.5845 0.106* O7 0.3711(3) 0.0703(6) 1.1284(2) 0.0930(18) C15 0.3673(5) 0.0212(8) 0.4149(3) 0.086(2) O8 0.4093(2) 0.3295(4) 0.92966(16) 0.0473(10) H15A 0.3489 0.0731 0.3803 0.129* O9 0.3170(3) 0.3737(5) 0.84763(17) 0.0641(14) H15B 0.3558 −0.0721 0.4068 0.129* O10 0.7918(3) 0.1680(5) 0.82648(18) 0.0594(12) H15C 0.4322 0.0345 0.4257 0.129* N2 0.6988(3) 0.0562(6) 0.7589(2) 0.0567(14) C16 0.4425(3) 0.1779(7) 0.5280(3) 0.062(2) H2A 0.6962 0.0050 0.7284 0.068* H16A 0.4462 0.0975 0.5514 0.092* C35 0.3342(3) 0.3444(6) 0.9693(2) 0.0434(15) H16B 0.4582 0.2538 0.5528 0.092* H35 0.2739 0.3365 0.9465 0.052* H16C 0.4851 0.1719 0.4980 0.092* C36 0.3476(4) 0.2258(6) 1.0134(2) 0.0468(15) C17 0.0338(3) 0.3624(8) 0.4842(3) 0.075(2) C37 0.2950(3) 0.2505(7) 1.0683(2) 0.0429(14) H17A 0.0105 0.2828 0.4643 0.113* H37 0.3160 0.3380 1.0839 0.051* H17B 0.0174 0.4394 0.4603 0.113* C38 0.1878(3) 0.2576(7) 1.0606(2) 0.0452(14) H17C 0.0072 0.3705 0.5213 0.113* C39 0.1465(3) 0.3800(6) 1.0266(3) 0.0462(16) C18 0.2186(4) 0.5749(8) 0.4241(3) 0.067(2) H39 0.1587 0.3677 0.9852 0.055* H18 0.2404 0.5196 0.3954 0.080* C40 0.1940(4) 0.5126(6) 1.0473(3) 0.0488(16) C19 0.1603(6) 0.6629(10) 0.4054(4) 0.115(3) H40 0.2322 0.4940 1.0840 0.059* H19A 0.1357 0.7216 0.4318 0.138* C41 0.2584(4) 0.5752(6) 1.0029(3) 0.0476(15) H19B 0.1421 0.6688 0.3653 0.138* C42 0.3451(4) 0.4849(6) 0.9952(3) 0.0461(15) Wang and Zhao: C34H49NO5S Ë 175

Table 2 (continued) Table 2 (continued)

Atom x y z Uiso*/Ueq Atom x y z Uiso*/Ueq

H42A 0.3852 0.5344 0.9708 0.055* C64 0.9525(4) 0.0605(8) 0.7872(3) 0.065(2) H42B 0.3785 0.4760 1.0338 0.055* H64 0.9565 0.1290 0.8150 0.078* C43 0.4520(4) 0.2132(8) 1.0334(3) 0.073(2) C65 1.0331(5) 0.0030(9) 0.7705(3) 0.075(2) − H43A 0.4622 0.1340 1.0570 0.109* C66 1.0267(5) 0.0990(9) 0.7311(4) 0.087(3) − H43B 0.4717 0.2906 1.0561 0.109* H66 1.0806 0.1398 0.7204 0.104* C67 0.9427(5) −0.1431(9) 0.7069(3) 0.090(3) H43C 0.4868 0.2071 0.9993 0.109* H67 0.9397 −0.2121 0.6792 0.108* C44 0.3095(4) 0.0911(7) 0.9854(3) 0.0570(17) C68 0.8620(5) −0.0849(8) 0.7235(3) 0.074(2) H44 0.3241 0.0210 1.0149 0.068* H68 0.8047 −0.1160 0.7075 0.089* C45 0.2025(4) 0.0957(8) 0.9747(3) 0.070(2) C69 1.1259(4) 0.0544(12) 0.7977(4) 0.131(4) H45A 0.1851 0.1642 0.9456 0.084* H69A 1.1335 0.0296 0.8386 0.196* H45B 0.1803 0.0102 0.9589 0.084* H69B 1.1278 0.1504 0.7943 0.196* C46 0.1560(4) 0.1253(7) 1.0303(3) 0.0632(19) H69C 1.1751 0.0159 0.7774 0.196* 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) water and dried with anhydrous Na2SO4 overnight. The H48A 0.2560 0.2154 1.1956 0.104* solvent was evaporated in vacuum and the residue was H48B 0.2075 0.0842 1.1695 0.104* chromatographed on silica gel (petroleum ether:ethyl acetate C49 0.1605(4) 0.2551(8) 1.1250(3) 0.0656(18) 2:1 v/v) to aord a pure product (1.29 g, yield: 74%; m.p. 67–69 H49A 0.1600 0.3453 1.1410 0.079* oC). Single crystals were obtained by slow evaporation from a H49B 0.0994 0.2161 1.1268 0.079* dichloromethane solution at room temperature. 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* Experimental details H50C 0.4179 0.0541 0.9340 0.126* Carbon-bound H atoms were placed in calculated positions C51 0.0401(3) 0.3872(8) 1.0283(3) 0.072(2) and were included in the renement using the riding model H51A 0.0253 0.4029 1.0681 0.109* U U H51B 0.0128 0.3041 1.0144 0.109* approximation, with iso(H) set to 1.2 eq(C). The H atoms of H51C 0.0159 0.4592 1.0035 0.109* the methyl group were allowed to rotate with a xed angle C52 0.2073(4) 0.5956(7) 0.9425(3) 0.0622(18) around the C—C bond to best t the experimental electron

H52 0.2107 0.5241 0.9166 0.075* density, with Uiso(H) set to 1.5Ueq(C). The H atoms of the C53 0.1612(5) 0.6945(8) 0.9225(4) 0.096(3) hydroxyl groups were allowed to rotate with a xed angle H53A 0.1548 0.7697 0.9460 0.115* around the C—O bond to best t the experimental electron H53B 0.1334 0.6925 0.8841 0.115* U C54 0.2960(4) 0.7079(7) 1.0284(3) 0.071(2) density (HFIX 147 in the SHELXL program [8]), with iso(H) H54A 0.3269 0.6927 1.0668 0.107* set to 1.5Ueq(O). H54B 0.2456 0.7695 1.0314 0.107* H54C 0.3392 0.7449 1.0030 0.107* Discussion 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) Pleuromutilins are important diterpenes which exhibit H56A 0.5184 0.2597 0.8661 0.073* high activities against drug-resistant Grampositive bacteria H56B 0.5124 0.4053 0.8398 0.073* and mycoplasmas in vitro and in vivo [1]. Pleuromutilins C58 0.5693(4) 0.2238(6) 0.7447(2) 0.0489(16) selectively inhibit bacterial protein synthesis through C59 0.5474(4) 0.1856(9) 0.6792(3) 0.080(2) interaction with prokaryotic ribosomes at the acceptor H59A 0.5055 0.1108 0.6764 0.120* and donor site (A- and P site, respectively) [2]. This H59B 0.6038 0.1617 0.6624 0.120* H59C 0.5192 0.2606 0.6581 0.120* unique antibacterial mechanism makes pleuromutilins C60 0.6293(4) 0.3482(7) 0.7502(3) 0.0652(19) display high antibacterial activities with no target-specic H60A 0.5963 0.4222 0.7314 0.098* cross-resistance to other antibiotics [3]. The modication H60B 0.6855 0.3329 0.7316 0.098* of pleuromutilin has led to three drugs: tiamulin [4], H60C 0.6441 0.3684 0.7912 0.098* valnemulin [5], and retapamulin [6]. We have been en- C61 0.6122(4) 0.1046(7) 0.7799(3) 0.0539(17) gaged in the design and preparation of the pleuromutilin H61A 0.6236 0.1310 0.8209 0.065* H61B 0.5677 0.0316 0.7781 0.065* derivatives with potential biological activities recently. C62 0.7826(4) 0.0884(7) 0.7854(3) 0.0475(16) Herein we report the X-ray crystal structure of the title C63 0.8665(4) 0.0194(7) 0.7638(3) 0.0502(16) compound which showed potential antibacterial activity. 176 Ë Wang and Zhao: C34H49NO5S

The crystal structure of the title compound consists of radiodurans in complex with tiamulin. Mol. Microbiol. 54 (2004)

C34H49NO5S molecules possessing a 5-6-8 tricyclic carbon 1287–1294. skeleton and a benzene ring, in which all bond lengths 3. Shang, R. F.; Wang, J. T.; Guo, W. Z.; Liang, J. P.: Ecient antibacterial agents: A review of the synthesis, biological are in normal ranges. The synthesized side chain of pleu- evaluation and mechanism of pleuromutilin derivatives. Curr. romutilin exhibits zig-zag conformation. Six intramolecular Top. Med. Chem. 13 (2013) 3013–3025. H-bonds are formed among the molecules. Also, there are 4. Burch, D. G.: Tiamulin activity against Brachyspira hyodysente- three intermolecular H-bonds (O1—H1··· O9, O2—H2··· O5, riae. Vet. Rec. 163 (2008) 760. N2—H2A··· O4, and O6—H6A··· O10 linking the molecules to 5. Stipkovits, L.; Ripley, P. H.; Tenk, M.; Glavits, R.; Molnar, T.; Fodor, L.: The ecacy of valnemulin (Econor) in the control chains along the a direction. of disease caused by experimental infection of calves with Mycoplasma bovis. Res. Vet. Sci. 78 (2005) 207–215. Acknowledgements: This work was supported by grants 6. Scangarella-Oman, N. E.; Shawar, R. M.; Bouchillon, S.; from Lanzhou Talent Innovation and Entrepreneurship Hoban, D.: Microbiological prole of a new topical antibacterial: Project (2015-RC-21). retapamulin ointment 1%. Expert Rev. Anti. Infect. Ther. 7 (2009) 269–279. 7. Agilent Technologies: CrysAlisPRO Software system, version References 1.171.37.33, Agilent Technologies UK Ltd, Oxford, UK 2014. 8. Sheldrick, G. M.: A short history of SHELX. Acta Crystallogr. A 64 1. Novak, R.; Shlaes, D. M.: The pleuromutilin antibiotics: A new (2008) 112–122. class for human use. Curr. Opin. Invest. Drugs 11 (2010) 182–191. 9. Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.; 2. Schlunzen, F.; Pyetan, E.; Fucini, P.; Yonath, A.; Harms, J. M.: Puschmann, H.: OLEX2: a complete structure solution, Inhibition of peptide bond formation by pleuromutilins: The renement and analysis program. J. Appl. Cryst. 42 (2009) structure of the 50 S ribosomal subunit from Deinococcus 339–341.