Z. Kristallogr. NCS 2018; 233(2): 283–285

Xing-An Cheng, Liu Zhan-Mei, Wu Bo, Huang Su-Qing, Xiong Xia-Ling and Jiang Xu-Hong*The crystal structure of a matrine derivative: 41S,7aS,12S,13aR,13bR)-12-(4-methylpiperazin-1-yl)dodecahydro-1H,5H,10H-dipyrido[2,1-f :3′,2′,1′-ij][1,6]naphthyridin-10-one, C20H34N4O

https://doi.org/10.1515/ncrs-2017-0282Received October 6, 2017; accepted January 17, 2018; availableonline February 9, 2018

AbstractC20H34N4O, triclinic, P1 (no. 1), a= 7.8545(6) Å, b=10.8802(9) Å, c= 12.3714(9) Å, α= 73.200(7)°, β=75.372(6)°, γ = 71.091(7)°, V = 942.65(13) Å3, Z= 2,Rgt(F)=0.0591, wRref(F2)= 0.1641, T = 293(2) K.

CCDC no.: 1548785

One of the two crystallographically independent titlemolecules, which are present in the asymmetric unit of thetitle crystal structure is shown in the figure1. Tables 1 and 2contain details on the crystal structure and measurementconditions and a list of the atoms including atomiccoordinates and displacement parameters.

Source of materialsThe synthesis of the title compound was carried out usingthe michael addition reaction. A mixture of sophocarpine(0.31 g, 1.25 mmol), N-methyl piperazine (0.5 mL, 2.5 mmol)were dissolved in 12 mL deionized water, and stirredvigorously at 60°. After 6 h, the crude reaction mixturewas collected and concentrated with a rotary evaporator.

*Corresponding author: Jiang Xu-Hong, Institute of Natural ProductChemistry, Zhongkai University of Agriculture and Engineering,Guangzhou, Guangdong 510225, China, e-mail: 47751664@qq.comXing-An Cheng, Liu Zhan-Mei, Wu Bo, Huang Su-Qing and XiongXia-Ling: Institute of Natural Product Chemistry, ZhongkaiUniversity of Agriculture and Engineering, Guangzhou, Guangdong510225, China

Table 1: Data collection and handling.

Crystal: Block, colorlessSize: 0.6×0.4×0.30 mmWavelength: Cu Kα radiation (1.54178 Å)μ: 0.60 mm−1

Diffractometer, scan mode: Multiwire proportional, φ andω-scans

2θmax, completeness: 74.3°, >96%N(hkl)measured, N(hkl)unique, Rint: 6049, 4265, 0.017Criterion for Iobs, N(hkl)gt: Iobs > 2 σ(Iobs), 4193N(param)refined: 453Programs: OLEX2 [1], SHELX [2]

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

Atom x y z Uiso*/Ueq

N1 0.1915(3) 0.4068(2) 0.3951(2) 0.0226(5)N1′ −0.1552(3) −0.0920(3) 0.5661(2) 0.0265(6)N16 0.2844(4) 0.6551(3) 0.1389(2) 0.0293(6)N16′ −0.1938(3) −0.3665(3) 0.8085(2) 0.0260(6)N19 0.6503(3) 0.8697(3) 0.1458(2) 0.0238(5)N19′ −0.4630(4) −0.6372(3) 0.7845(2) 0.0280(6)N22 0.8348(3) 1.0756(2) 0.0838(2) 0.0225(5)N22′ −0.6559(4) −0.8387(3) 0.8490(2) 0.0286(6)O18 0.3094(3) 0.7246(2) −0.05300(18) 0.0263(5)O18′ −0.1262(3) −0.4865(2) 0.9819(2) 0.0320(5)C2 0.0853(5) 0.3141(3) 0.4069(3) 0.0310(7)H2A −0.0128 0.3224 0.4724 0.037*H2B 0.1634 0.2235 0.4212 0.037*C3 0.0047(4) 0.3401(3) 0.3003(3) 0.0300(7)H3A −0.0806 0.4282 0.2888 0.036*H3B −0.0620 0.2753 0.3106 0.036*C3′ 0.0415(6) −0.0248(4) 0.6520(3) 0.0420(9)H3′A −0.0516 −0.0082 0.7185 0.050*H3′B 0.1166 0.0358 0.6360 0.050*C4 0.1550(4) 0.3307(3) 0.1952(3) 0.0251(6)H4A 0.2295 0.2391 0.2014 0.030*H4B 0.1009 0.3572 0.1269 0.030*C4′ 0.1592(5) −0.1673(4) 0.6783(3) 0.0357(8)H4′A 0.2029 −0.1847 0.7494 0.043*H4′B 0.2646 −0.1796 0.6175 0.043*C5 0.2743(4) 0.4205(3) 0.1853(2) 0.0212(6)H5 0.3814 0.3989 0.1261 0.025*C5′ 0.0513(4) −0.2664(3) 0.6892(3) 0.0244(6)H5′ 0.1384 −0.3547 0.6911 0.029*C6 0.3444(4) 0.3961(3) 0.2971(2) 0.0224(6)H6 0.4262 0.3055 0.3117 0.027*C6′ −0.0410(4) −0.2303(3) 0.5847(2) 0.0241(6)

Open Access. ©2018 Xing-An Cheng et al., published by De Gruyter. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

284 | Cheng et al.: C20H34N4O

Table 2 (continued)

Atom x y z Uiso*/Ueq

H6′ 0.0547 −0.2396 0.5169 0.029*C7 0.4543(4) 0.4962(3) 0.2855(2) 0.0259(6)H7 0.5604 0.4813 0.2242 0.031*C7′ −0.1561(5) −0.3278(3) 0.5995(3) 0.0337(7)H7′ −0.0728 −0.4178 0.6049 0.040*C8 0.5248(4) 0.4675(4) 0.3984(3) 0.0312(7)H8A 0.6129 0.3806 0.4095 0.037*H8B 0.5861 0.5338 0.3937 0.037*C8′ −0.2404(7) −0.2920(5) 0.4925(3) 0.0515(11)H8′A −0.1442 −0.3064 0.4269 0.062*H8′B −0.3176 −0.3496 0.5022 0.062*C9′ −0.3525(6) −0.1484(5) 0.4705(3) 0.0508(11)H9′A −0.4572 −0.1362 0.5318 0.061*H9′B −0.3973 −0.1256 0.3990 0.061*C10 0.2607(4) 0.3762(3) 0.5017(2) 0.0283(6)H10A 0.3386 0.2855 0.5145 0.034*H10B 0.1586 0.3817 0.5651 0.034*C10′ −0.2380(5) −0.0573(4) 0.4639(3) 0.0396(9)H10C −0.1420 −0.0622 0.3970 0.048*H10D −0.3143 0.0339 0.4545 0.048*C11 0.3322(5) 0.6425(3) 0.2496(3) 0.0293(7)H11 0.2183 0.6513 0.3057 0.035*C11′ −0.2967(5) −0.3275(3) 0.7127(3) 0.0302(7)H11′ −0.3693 −0.2348 0.7097 0.036*C12 0.4095(5) 0.7567(3) 0.2446(3) 0.0290(7)H12A 0.3113 0.8385 0.2431 0.035*H12B 0.4608 0.7378 0.3132 0.035*C12′ −0.4312(4) −0.4098(3) 0.7371(3) 0.0294(7)H12C −0.5366 −0.3769 0.7921 0.035*H12D −0.4731 −0.3998 0.6669 0.035*C13 0.5540(5) 0.7756(3) 0.1413(3) 0.0284(7)H13 0.6452 0.6889 0.1434 0.034*C13′ −0.3454(5) −0.5552(3) 0.7838(3) 0.0311(7)H13′ −0.2305 −0.5822 0.7317 0.037*C14 0.4740(4) 0.8080(3) 0.0334(2) 0.0219(6)H14A 0.4038 0.9008 0.0197 0.026*H14B 0.5739 0.7978 −0.0310 0.026*C14′ −0.2974(4) −0.5693(3) 0.8993(3) 0.0232(6)H14C −0.4091 −0.5576 0.9556 0.028*H14D −0.2216 −0.6591 0.9232 0.028*C15 0.3523(4) 0.7233(3) 0.0364(2) 0.0206(6)C15′ −0.1976(4) −0.4707(3) 0.8991(2) 0.0224(6)C17 0.1746(4) 0.5678(3) 0.1459(3) 0.0259(6)H17A 0.1439 0.5822 0.0711 0.031*H17B 0.0614 0.5900 0.1992 0.031*C17′ −0.0879(4) −0.2752(3) 0.8003(2) 0.0242(6)H17C −0.0247 −0.3056 0.8652 0.029*H17D −0.1699 −0.1872 0.8034 0.029*C20 0.8181(4) 0.8640(3) 0.0611(3) 0.0229(6)H20A 0.7885 0.9060 −0.0150 0.027*H20B 0.8861 0.7718 0.0622 0.027*C20′ −0.6319(5) −0.6276(3) 0.8692(3) 0.0316(7)H20C −0.6974 −0.5346 0.8663 0.038*H20D −0.6031 −0.6683 0.9456 0.038*C21 0.9328(4) 0.9354(3) 0.0883(3) 0.0250(6)H21A 0.9625 0.8928 0.1642 0.030*

Table 2 (continued)

Atom x y z Uiso*/Ueq

H21B 1.0463 0.9291 0.0336 0.030*C21′ −0.7502(5) −0.6981(3) 0.8439(3) 0.0312(7)H21C −0.8631 −0.6903 0.8993 0.037*H21D −0.7810 −0.6556 0.7682 0.037*C23 0.6568(4) 1.0873(3) 0.1595(3) 0.0265(7)H23A 0.5885 1.1806 0.1493 0.032*H23B 0.6751 1.0547 0.2386 0.032*C23′ −0.4789(5) −0.8511(3) 0.7706(3) 0.0318(7)H23C −0.5000 −0.8153 0.6921 0.038*H23D −0.4131 −0.9447 0.7783 0.038*C24 0.5463(4) 1.0092(3) 0.1358(3) 0.0257(6)H24A 0.4323 1.0155 0.1901 0.031*H24B 0.5175 1.0468 0.0592 0.031*C24′ −0.3633(5) −0.7778(3) 0.7950(3) 0.0315(7)H24C −0.3358 −0.8163 0.8718 0.038*H24D −0.2488 −0.7864 0.7411 0.038*C25 0.9419(5) 1.1413(3) 0.1172(3) 0.0291(7)H25A 0.9615 1.0989 0.1943 0.044*H25B 0.8770 1.2336 0.1128 0.044*H25C 1.0576 1.1346 0.0664 0.044*C25′ −0.7675(6) −0.9021(4) 0.8168(3) 0.0367(8)H25D −0.7833 −0.8621 0.7386 0.055*H25E −0.8848 −0.8904 0.8660 0.055*H25F −0.7077 −0.9956 0.8244 0.055*

The concentrated solution was purified by the silica gelcolumn chromatography eluting with ethanol. The productwas dissolved in petroleum ether and heated at 80° for1–2 min, and then 1% active carbon was added into thesolution with continued stirring vigorously by a glass rod.After standing for 2 minutes, the solution was filtratedwith filter tissue into a 10 mL glass sample bottle. Thetitle compound (systematic name (41S,7aS,12S,13aR,13bR)-12-(4-methylpiperazin-1-yl)dodecahydro-1H,5H,10H-dipyrido[2,1-f :3′,2′,1′-ij][1,6]naphthyridin-10-one) was crystallized frompetroleum ether, whereupon a few colorless, rod-shapecrystals suitable for X-ray diffraction analysis were obtained.

Experimental detailsHydrogen atomswere placed in calculated positions andwereincluded in the refinement in the riding model approxima-tion, with U iso(H) set to 1.2Ueq(C) [1, 2].

DiscussionAs a major quinolizindine alkaloid isolated from Sophoraflavescens AIT, matrine has attracted considerable attentiondue to its broad biological activities, such as anti-inflammatory properties, notable antiviral activities,anti-tumor, anti-nociceptive effects [3–7]. The matrine isalso wildly used as a biological pesticide due to its notableinsecticidal activity [8, 9]. Therefore, it is interesting to carry

Cheng et al.: C20H34N4O | 285

out the structure modification of matrine to evaluate itsbiological activities [10–13].

The skeletons of matrine and its derivatives contain aquinolizidinic A-B ring system fused with a quinolizidinoneC—D ring system [14]. The stable property of D ring inmatrine makes it hard to be modified. Sophocarpine isusually used as the starting material for structure modifi-cation of matrine because it contains an a,b-unsaturatedcarbonyl group that is reactive toward a variety of usefulnucleophiles.

In the present study, the title compound was synthe-sized by introducing N-methyl piperazine group to C13 ofsophocarpine and a bond (C13—N19) with length 1.476(4) Åwas formed in this compound, which makes its C13 translateinto chiral carbon with a configuration of S (cf. the figure).The single bond length of C13—C14 [1.520(4) Å] in D ringof the title compound is longer in comparison with that ofthe double bond in sophocarpine, 1.3229(18) Å. As a matterof fact, the bond lengths of C12—C13[1.493(4) Å],C11—C12[1.531(4) Å] and C14—C15[1.516(4) Å] in the title compound donot change significantly compared to that of sophocarpine,being 1.4925(16) Å, 1.529(16) Å and 1.478(16) Å respectively.The bond angle of C12—C13—C14with a value of 108.2(3)° in Dring of the title compoundaswell as the other angles are in theexpected ranges [15]. All these indicate that the introductionof N-methyl piperazine group to C13 of D ring mainly affectsthe length of the near bonds, the angle and the configurationof C13. In addition, the mean plane of the N-methyl piperazylgroup is nearly coplanar to the plane of group C14—C13—12.The molecules were packed in the crystal structure withoutany hydrogen bonds and the benzene rings of molecules inthe crystal structure show no π–π interaction.

Acknowledgements: This work was sponsored by theNational Natural Science Foundation of China(No. 21406274, 201376281). Special Fund of Scientificand Technological Innovation Research for CollegeStudents in Guangdong Province, China (Climbing Programof College Students in Guangdong Province, China)(K1178350111). National Training Program of Innovationand Entrepreneurship for College Students (201711347012).Innovative Training Program for College Students inGuangdong (201711347055).

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