• <tr id="yyy80"></tr>
  • <sup id="yyy80"></sup>
  • <tfoot id="yyy80"><noscript id="yyy80"></noscript></tfoot>
  • 99热精品在线国产_美女午夜性视频免费_国产精品国产高清国产av_av欧美777_自拍偷自拍亚洲精品老妇_亚洲熟女精品中文字幕_www日本黄色视频网_国产精品野战在线观看 ?

    Circularly polarized luminescence of talarolactones (+)/(?)-A and(+)/(?)-C: The application of CPL-calculation in stereochemical assignment

    2022-09-15 03:10:58GuiyngXiLingynWngHunXiYuzhuoWuYnnWngHiyuHuShengLin
    Chinese Chemical Letters 2022年9期

    Guiyng Xi, Lingyn Wng, Hun Xi, Yuzhuo Wu, Ynn Wng, Hiyu Hu,?,Sheng Lin,c,??

    a Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China

    b State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

    c Key Laboratory for Qinghai-Tibet Plateau Phytochemistry of Qinghai Province, College of Pharmaceutical, Qinghai Nationalities University, Xining 810007,China

    ABSTRACT Two pairs of fluorescent natural products, talarolactones (+)/(?)-A and (+)/(?)-C [(+)/(?)-1 and(+)/(?)-2], were discovered and characterized as a new family of circularly polarized luminescence-active small organic molecules (CPL-SOMs) with high fluorescence efficiency and fascinating CPL properties.The CPL (|glum|) levels of enantiomerically pure (+)/(?)-1 and (+)/(?)-2 in solution falls into the usual range(10?5?10?3) considering their pure organic nature, but the sign of CPL were found to be closely related to the absolute configuration of C-8.The high agreement of the measured CPL spectra of (+)/(?)-1 and(+)/(?)-2 with the time-dependent density functional theory (TDDFT) calculated ones demonstrated the usefulness of CPL-calculation as a unique method for stereochemical assignment.This study may open up a new perspective for the stereochemical studies and the future development of CPL materials.

    Keywords:Circularly polarized luminescence Natural products Stereochemical assignment Talarolactones (+)/(?)-A Talarolactones (+)/(?)-C

    Circularly polarized luminescence (CPL), which measures the differential of right- and left-circularly polarized spontaneous emission from intrinsically chiral fluorophore or fluorophore in a chiral environment, is extensively observed in nature [1–3] and it has been attracting increasing attentions in recent years [4–7].Besides the CPL materials derived from synthesis,such as chiral lanthanide complexes [8,9], axial chirality biphenyl groups [10], [2.2]paracyclophane derivatives [11], helicenes [12–14],supramolecular and polymeric structures [15,16], natural products with a variety of structural features might also be the great resources of CPL small organic molecules (CPL-SOMs), which are considered to be a promising class of materials for applications of CPL.Nonetheless, natural CPL-SOMs has been poorly reported except for some simple cyclic ketones that used as model for theoretical researches [17,18].

    Depending on the same general aspects of molecular structure, circular dichroism (CD) and CPL are mutually complementary probes for the structural features of chiral molecules.As the CPL is typically responsible to the excited state (S1) to ground state(S0) electronic transition, information obtained from CPL is more selective and specific than that from CD.However, due to the limitations of instruments and appropriate molecular models, studies on the CPL spectra-structure relationships have been heretofore rather limited [19–21] in contrast to the tremendous efforts that have been devoted to the CD.To date, there is few empirical rules for the explanation and/or prediction of CPL properties including the CPL signs [22,23], resulted in the limitation on theoretical investigation.Quantum chemical calculations of CPL have been used to interpret of CPL data of some basic chiral compounds and CPL emitters [24–26], indicating that it is possible to apply CPL-calculation in the stereochemical assignment.However, to the best of our knowledge, the application of CPL-calculation in the determination of absolute configuration of chiral carbons has poorly been addressed [27].Therefore, with further investigation into the interpretation of CPL of chiral compounds, applications of CPL to the structure elucidation may open up a new perspective for stereochemical studies.

    Fig.1.Fluorescent images of (±)-1 and (±)-2 under UV light (365 nm) and chemical structures of (+)/(?)-1 and (+)/(?)-2.

    Fungi are hyperdiverse and one of the best sources for natural pigments [17], however, natural skeletons with CPL properties have been rarely explored.As part of our ongoing effort to mining functional secondary metabolites from fungi [28–31], chemical investigations on a strain of endophytic fungusOphiosimulans tanacetiwere carried out.During the isolation process, a strong blue luminescence emission of a fraction under ultraviolet light radiation caught our attention, which prompted us to investigate the origins of the fluorescence.Eventually, two pairs of sulfur-containing isocoumarin derivates, talarolactones (+)/(?)-A and (+)/(?)-C [(+)/(?)-1 and (+)/(?)-2] (Fig.1), were characterized as a new family of CPL-SOMs with normal CPL levels(|glum|: 4.0×10?4~5.1×10?4) and strong fluorescent property(ФF: 42.17%–44.62%).The presence of chiral carbons in the structure is the only chiral element that responsible for their chiroptical dissymmetry, making them ideal molecular models for the study of CPL spectra-structure relationships.The systematic analysis of the signs of the CPL spectra, assisted by the time-dependent density functional theory (TDDFT) calculations, leading us to conclude that the right- and left- handed twist of the chromophores (consisting of the lactone C=O and aromatic ring) in the excited state exhibit (+)- and (?)-CPL, respectively.Further structure conformation analysis indicated that the absolute configuration of C-8 closely related to the dihedral angles (θ) between the chromophores.

    Bearing all these ideas in mind, herein we present, for the first time, the application of CPL-calculations in stereochemical assignments.It was successfully applied to the determination of the stereoconfiguration of (?)-1, (+)-1, (?)-2, (+)-2, and some reported CPL-active SOMs [(1S,4R)-3, (1R,4S)-3, (?)-4, (+)-4, (?)-5 and (+)-5].We strongly believe that the results achieved with this work may represent an important milestone for the stereochemical studies and the future development of CPL materials.

    Compound 1 was obtained as a yellow, amorphous powder,and possessed a molecular formula of C13H12O5S assigned by HRESIMS data for the [M+H]+ion atm/z281.0477 (calcd.for C13H13O5S, 281.0478), requiring 8 degrees of unsaturation.A detailed comparation of its UV, IR, and 1D- and 2D-NMR spectra with talarolactone A, which had been recently reported as an optically pure compound isolated from the endolichenic fungusTalaromycessp., revealed that the planar structure of 1 should be identical with talarolactone a (Table S1 in Supporting information) [32].However, negligible optical activity indicated that 1 was a pair of racemic mixture.Subsequent chiral resolution of 1 afforded the enantiomers (?)-1 and (+)-1, displaying mirror image CD curves and opposite specific rotation [(?)-1:?197.5(c0.12, MeOH); (+)-1:+203.5 (c0.09, MeOH)], and the final assignment of the absolute configurations of (?)-1 (8S,9R) and(+)-1 (8R,9S) were achieved by comparison of their experimental CD spectra with TDDFT calculated ones combined with the analysis of their single-crystal X-ray diffraction data using Cu Kαradiation(Figs.2A and B).Accordingly, the significant difference of the specific rotation between the (+)-1+203.5 (c0.09, MeOH)]and talarolactone A+36.85 (c0.445, MeOH)] concluded that the reported talarolactone A should be a partial racemic mixture,which was confirmed by its weak CD Cotton bands (especially for the first Cotton band around 385 nm, Fig.S13 in Supporting information).Consequently, the enantiomers (?)-1 and (+)-1 should be given the names of (?)-talarolactone A and (+)-talarolactone A,respectively.

    Fig.2.(A) Experimental and computational ECD and CPL spectra for (?)-1 and(+)-1.(B) X-ray ORTEP drawing of (?)-1 and (+)-1 depicting their absolute configurations.

    Compound 2, obtained as yellow powder, possesses the same molecular formula (C13H12O5S) as 1, as determined from NMR data and HRESIMS [M+H]+ion atm/z281.0477 (calcd.for C13H13O5S,281.0478).The UV, IR, and CD data of 2 were also resembled to those of 1.A side-by-side comparison of the1H and13C NMR data of 2 with those of 1 revealed that the only difference between 1 and 2 was the small change in chemical shifts from C-8 to C-11.These findings, combined with the 2D NMR data and the small coupling constant between H-8 and H-9 (J=6.4 Hz), affirmed that 2 was the C-8?C-9 diastereomer of 1.Since the small specific rotation of 2+30.5 (c0.08, MeOH)] was measured,its partial racemic nature was presumed and verified by the chiral HPLC separation.Subsequent preparation led to the acquisition of (?)-2?182.9 (c0.04, MeOH)] and (+)-2+183.2(c0.13, MeOH)].Finally, the absolute configurations of (?)-2 and(+)-2 were assigned as 8S,9Sand 8R,9R, respectively, according to the comparing of the experimental and TDDFT-simulated CD spectra, as well as the single-crystal X-ray diffraction data of (+)-2(Figs.3A and B).

    With the observation of strong blue fluorescence under ultraviolet light radiation, (+)/(?)-1 and (+)/(?)-2 are responsible for the fluorescence fraction mentioned above.Then the photophysical properties of (+)/(?)-1 and (+)/(?)-2 were studied.Each of(+)/(?)-1 and (+)/(?)-2 showed the longest wavelength UV absorbance at approximately 395 nm and fluorescence emission centered at approximately 480 nm (Figs.S14 and S28 in Supporting information) with high fluorescence quantum yields (φF) in MeOH ranged between 42.17% and 44.62%, and the fluorescence lifetime(τs) of (?)-1, (+)-1, (?)-2 and (+)-2 were determined to be 8.81,9.13, 14.12, and 14.15 ns, respectively.Interestingly, when the living HO-8910 cells were treated with (±)-1 and (±)-2 at 50 μmol/L for 0.5 h, (±)-1 and (±)-2 could readily accumulated in the cells without cytotoxicity as shown in the cellular images (Fig.4), heralding their promising application in cellular imaging.

    Fig.3.(A) Experimental and computational ECD and CPL spectra for (?)-2 and (+)-2.(B) X-ray ORTEP drawing of (+)-2 depicting its absolute configuration.

    Fig.4.Representative cellular fluorescence imaging of HO-8910 cells treated with(±)-1 and (±)-2.(1) brightfield (top); (2) blue channel λex=405 nm (middle); (3)merged (bottom).

    Considering the presence of chiral elements in the structures of the enantiomers, we also investigated the CPL properties of(+)/(?)-1 and (+)/(?)-2 to further explore their potential applications.To our delight, virtually mirror images of CPL spectra and almost oppositeglumvalues were detected for each pair of enantiomers, and the emission wavelengths of the CPL signals correspond well to the fluorescence emission wavelengths.In addition, the signs of the CPL were identical to their first Cotton CD band (lowest-energy band), which is in consistent with the general trends for the CD and CPL spectra (Figs.2A and 3A).To the best of our knowledge, they were the first examples of natural fluorescent SOMs that demonstrate CPL activity controlled by chiral carbon with a high fluorescence quantum yield.

    Fig.5.Calculated HOMOs and LUMOs of (?)-1 and (+)-1, and the relation between the twist arrangement of the key chromophores and the respective positive or negative CPL signatures.

    To further shed light on the photophysical and chiroptical properties of (+)/(?)-1 and (+)/(?)-2, we conducted the DFT and TDDFT calculations at the B3LYP/6-311G+(d,p) level.Based on the calculated geometries in the S0and S1states, the entire structural difference was mainly attributed to the change of the dihedral angle between the lactone C=O and the benzene ring (Table S9 in Supporting information).The highest occupied molecular orbitals(HOMOs) and the lowest unoccupied molecular orbitals (LUMOs) of(+)/(?)-1 and (+)/(?)-2 (Fig.5 and Fig.S38 in Supporting information) were all delocalized over the entire skeleton, with a slightly less distribution on the lactone carbonyl in the HOMOs.Besides,the CPL and the first Cotton CD band related transitions between S0and S1were attributed to the electronic transition between HOMOs and LUMOs.Thus, the chiroptical response were probably related to the planar asymmetry of the lactone ring.

    Detailed analysis of the structural constructions revealed that the signs of the CPL could be interpreted from the direction of the twist of the lactone C=O and the benzene ring, namely, clockwiseand counter clockwise-twist exhibit (+)- and (?)-CPL, respectively(Fig.5).Similar twist rule has been apparent in the explanation of some Cotton effects in CD spectra, but now turned out to be also applicable to the CPL signs.Recently, several related approaches for other chromophores have been reported.Considering the relatively rigid structures of (+)/(?)-1 and (+)/(?)-2, it could be easily speculated that the signs of their CPL were also restricted to the absolute configuration of C-8, and it was confirmed by the well matched calculated and experimental CPL spectra (Figs.2A and 3A).

    Motived by our successful CPL-calculation for 1 and 2, it could be speculated that the application of the CPL-calculation might be a promising unique method for the stereochemical assignment as a supplementary of CD-calculation.To verify this speculation and the reliability of our calculation method, TDDFT calculations of the fluorescence and CPL properties of the literature reported CPL-SOMs,(1S,4R)-camphorquinone [(1S,4R)-3] and (1R,4S)-camphorquinone[(1R,4S)-3] (Fig.6) [25], were performed.As expected, both the calculated fluorescence (Fig.S39 in Supporting information) and CPL spectra (Fig.S40 in Supporting information) met well with their reported experimental and theoretical calculation results, which verified our CPL-calculation method and made the absolute configuration of (1S,4R)-3 and (1R,4S)-3 successfully distinguished.

    Fig.6.Chemical structures of compounds 3?5.

    To further extend the application scope of the CPL-calculation,another pair of CPL-SOMs, (+)-10,10′-spirobi(indeno[1,2-b][1]benzothiophene) [(+)-4] and (?)-10,10′-spirobi(indeno[1,2-b][1]benzothiophene) [(?)-4] [33], were introduced to our investigation.(+)-4 and (?)-4 were reported as a pair of spiro-chiral enantiomers which showed mirror image CPL curves; however,their absolute configurations were not determined by the authors.To assign the absolute configuration, we calculated the CPL spectra of (+)-4 and (?)-4, which fully agreed with their experimental CPL information.By this approach, the absolute configurations of (+)-4 and (?)-4 could be assigned asRandS, respectively, which was confirmed by the ECD-calculations(Figs.S41 and S42 in Supporting information).Simultaneously, the absolute configurations of another pair of CPL-SOMs, (+)-10,10′-spirobi(indeno[1,2-b][1]benzothiophene) 5,5-dioxide and (?)-10,10′-spirobi(indeno[1,2-b][1]benzothiophene) 5,5-dioxide [(+)-5 and (?)-5] [33], were determined by CPL-calculation (Figs.S43 and S44 in Supporting information).Consequently, the above findings demonstrated that the CPL-calculation method is straightforward and reliable, and it can be applied for the determination of absolute configuration of chiral carbons.

    It has been over seventy years since the first measurement of CPL activity, however, to the best of our knowledge, this work presents the first proofs of natural fluorescent SOMs that demonstrate CPL properties.In contrast to the reported CPL emitters that generate CPL from the dissymmetry of different aromatic planes,(+)/(?)-1 and (+)/(?)-2 represent a new family of CPL-SOMs.We strongly believe that, although with moderate |glum| values, here reported can be considered as a starting point for the discovery of CPL-SOMs from natural products.

    Remarkably, the results of TDDFT calculations shed further light on the CPL spectra-structure relationships and an important step forward of the application of CPL-calculation to the stereochemical studies has been taken.As CPL reflects the structural properties of the luminescent excited states, the more selective and specific CPL-calculations might be a powerful supplement of the NMR/OR/ECD/VCD-calculations in the stereochemical studies and the stereochemical studies is herein extended to the excited states.In addition, with only the excited states responsible for the CPL being calculated, CPL-calculations will be more efficient than the NMR/OR/ECD/VCD-calculations, and the computational expense will be much reduced.

    Declaration of competing interest

    The authors declare no conflict of interest.

    Acknowledgments

    This work was supported by the National Natural Science Foundation of China (Nos.81803397, 82073978 and 22122705), Beijing Natural Science Foundation (No.JQ18026) and Innovation Team of Medicinal Material Resource Protection and High Value Utilization in Qinghai Province (No.2021XJPI02).

    Supplementary materials

    Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.cclet.2022.03.032.

    老司机午夜十八禁免费视频| 免费在线观看影片大全网站| 一边摸一边抽搐一进一小说| 亚洲第一电影网av| 身体一侧抽搐| 午夜福利在线观看吧| 侵犯人妻中文字幕一二三四区| 人成视频在线观看免费观看| 国产精品久久视频播放| 国产精品美女特级片免费视频播放器 | 国产精品永久免费网站| 最新美女视频免费是黄的| 国产99久久九九免费精品| 熟妇人妻久久中文字幕3abv| 日本成人三级电影网站| 日韩欧美国产一区二区入口| 精品国产美女av久久久久小说| 精品国产美女av久久久久小说| 19禁男女啪啪无遮挡网站| 免费观看人在逋| 久久中文字幕一级| 欧美日韩亚洲综合一区二区三区_| 亚洲精品美女久久久久99蜜臀| 欧美日韩亚洲综合一区二区三区_| 国产精华一区二区三区| 国产精华一区二区三区| 久久久精品国产亚洲av高清涩受| 狂野欧美激情性xxxx| 久久热在线av| 波多野结衣巨乳人妻| 亚洲av五月六月丁香网| 妹子高潮喷水视频| 国产亚洲精品第一综合不卡| 99re在线观看精品视频| 日韩三级视频一区二区三区| 大型av网站在线播放| 欧美乱妇无乱码| 国产日本99.免费观看| 国产又黄又爽又无遮挡在线| 日韩国内少妇激情av| 中文亚洲av片在线观看爽| 天天躁狠狠躁夜夜躁狠狠躁| 精品乱码久久久久久99久播| 亚洲男人天堂网一区| 一个人免费在线观看的高清视频| 叶爱在线成人免费视频播放| 欧美成人一区二区免费高清观看 | 欧美+亚洲+日韩+国产| 伊人久久大香线蕉亚洲五| 欧美黑人精品巨大| 亚洲精品美女久久av网站| 国产黄a三级三级三级人| 国产av不卡久久| 亚洲无线在线观看| 欧美日韩亚洲综合一区二区三区_| 国产精品av久久久久免费| 久久天堂一区二区三区四区| 99精品欧美一区二区三区四区| 久久久久久久久久黄片| 女生性感内裤真人,穿戴方法视频| 国产精品精品国产色婷婷| 亚洲国产精品成人综合色| 男人的好看免费观看在线视频 | 国产日本99.免费观看| 欧美日韩亚洲国产一区二区在线观看| 免费在线观看视频国产中文字幕亚洲| www日本黄色视频网| 两个人视频免费观看高清| 特大巨黑吊av在线直播 | 国产亚洲av嫩草精品影院| 久久午夜综合久久蜜桃| 老熟妇仑乱视频hdxx| 女生性感内裤真人,穿戴方法视频| 精品熟女少妇八av免费久了| 一区二区三区国产精品乱码| 无遮挡黄片免费观看| 免费女性裸体啪啪无遮挡网站| av福利片在线| 国内久久婷婷六月综合欲色啪| 国产亚洲精品综合一区在线观看 | 国产一级毛片七仙女欲春2 | svipshipincom国产片| 欧美国产精品va在线观看不卡| 国产在线观看jvid| 一边摸一边抽搐一进一小说| 免费一级毛片在线播放高清视频| 精品久久久久久,| 一夜夜www| 色av中文字幕| 亚洲中文字幕一区二区三区有码在线看 | 手机成人av网站| 久热这里只有精品99| 午夜福利在线观看吧| 久久人妻av系列| 精品一区二区三区视频在线观看免费| АⅤ资源中文在线天堂| 久久久精品国产亚洲av高清涩受| 女性被躁到高潮视频| 久久精品国产亚洲av香蕉五月| 国产精品久久视频播放| 国产激情偷乱视频一区二区| 人人妻人人澡欧美一区二区| 夜夜爽天天搞| 国产精品电影一区二区三区| 午夜影院日韩av| 欧美zozozo另类| 久久久精品国产亚洲av高清涩受| 老司机福利观看| 精品国内亚洲2022精品成人| 黄色a级毛片大全视频| 亚洲av中文字字幕乱码综合 | 制服丝袜大香蕉在线| 午夜免费激情av| e午夜精品久久久久久久| 国产在线精品亚洲第一网站| 不卡av一区二区三区| 日韩欧美国产一区二区入口| 一二三四社区在线视频社区8| 少妇裸体淫交视频免费看高清 | 欧美日本亚洲视频在线播放| 亚洲av美国av| 久久精品影院6| 桃红色精品国产亚洲av| 99精品久久久久人妻精品| 久久午夜亚洲精品久久| xxxwww97欧美| 成年版毛片免费区| 久久久久久国产a免费观看| 欧美色欧美亚洲另类二区| 免费在线观看视频国产中文字幕亚洲| www日本黄色视频网| 老鸭窝网址在线观看| 91大片在线观看| 一进一出抽搐gif免费好疼| 黄色视频,在线免费观看| 午夜福利成人在线免费观看| 久久婷婷成人综合色麻豆| 亚洲精品国产精品久久久不卡| 精品一区二区三区四区五区乱码| 国产乱人伦免费视频| 欧美黄色片欧美黄色片| 午夜激情福利司机影院| av免费在线观看网站| 日本精品一区二区三区蜜桃| 女人被狂操c到高潮| 黄色成人免费大全| 午夜福利免费观看在线| 国产av一区在线观看免费| 国产一区二区三区视频了| 免费高清在线观看日韩| 伦理电影免费视频| 国产男靠女视频免费网站| 啪啪无遮挡十八禁网站| 黄色毛片三级朝国网站| 日韩成人在线观看一区二区三区| 欧美性猛交黑人性爽| 色精品久久人妻99蜜桃| 亚洲色图 男人天堂 中文字幕| 午夜成年电影在线免费观看| 黄片播放在线免费| 韩国av一区二区三区四区| 国产精品国产高清国产av| 一进一出抽搐gif免费好疼| 久久人人精品亚洲av| 国产午夜精品久久久久久| 1024视频免费在线观看| 久久草成人影院| 成人18禁高潮啪啪吃奶动态图| 免费在线观看日本一区| 无限看片的www在线观看| 国产精品98久久久久久宅男小说| 亚洲专区中文字幕在线| 免费电影在线观看免费观看| 国内毛片毛片毛片毛片毛片| 中文字幕人妻熟女乱码| 亚洲天堂国产精品一区在线| 欧美国产精品va在线观看不卡| 悠悠久久av| 男女做爰动态图高潮gif福利片| 久久中文字幕一级| 国产亚洲av嫩草精品影院| 国内久久婷婷六月综合欲色啪| 国产伦在线观看视频一区| 最好的美女福利视频网| 男人的好看免费观看在线视频 | 老熟妇仑乱视频hdxx| or卡值多少钱| 久久国产精品人妻蜜桃| 丁香欧美五月| 午夜免费激情av| 在线观看舔阴道视频| 午夜福利一区二区在线看| 人人妻人人澡人人看| 又黄又爽又免费观看的视频| or卡值多少钱| 日韩大尺度精品在线看网址| 久久婷婷人人爽人人干人人爱| 别揉我奶头~嗯~啊~动态视频| 又黄又粗又硬又大视频| 哪里可以看免费的av片| 国产成人欧美在线观看| 18禁观看日本| 俺也久久电影网| 黑人操中国人逼视频| 国产蜜桃级精品一区二区三区| 可以在线观看的亚洲视频| 亚洲va日本ⅴa欧美va伊人久久| 男女床上黄色一级片免费看| 99热这里只有精品一区 | 免费一级毛片在线播放高清视频| 国产私拍福利视频在线观看| 欧美一级毛片孕妇| 亚洲 国产 在线| 久久精品国产亚洲av高清一级| 精品日产1卡2卡| 精品国产国语对白av| 国产99白浆流出| 男女午夜视频在线观看| 国产精品自产拍在线观看55亚洲| 无人区码免费观看不卡| 久久久久久久久免费视频了| 成人亚洲精品一区在线观看| 免费看美女性在线毛片视频| 首页视频小说图片口味搜索| 搡老熟女国产l中国老女人| 91字幕亚洲| 一区福利在线观看| 宅男免费午夜| 女生性感内裤真人,穿戴方法视频| 香蕉丝袜av| 高清毛片免费观看视频网站| 日韩欧美在线二视频| 国产精品亚洲av一区麻豆| 一级毛片女人18水好多| 亚洲国产欧美网| 日韩欧美在线二视频| 老司机午夜十八禁免费视频| 亚洲精品久久国产高清桃花| 叶爱在线成人免费视频播放| 岛国视频午夜一区免费看| 天天躁狠狠躁夜夜躁狠狠躁| 999精品在线视频| 亚洲国产精品合色在线| 免费在线观看日本一区| 国产亚洲欧美精品永久| 亚洲一卡2卡3卡4卡5卡精品中文| 亚洲av熟女| 露出奶头的视频| 精品乱码久久久久久99久播| 成人三级黄色视频| 身体一侧抽搐| 国产精品1区2区在线观看.| 亚洲国产日韩欧美精品在线观看 | 日本a在线网址| 19禁男女啪啪无遮挡网站| 一区福利在线观看| 亚洲精品一区av在线观看| 一边摸一边做爽爽视频免费| 中文字幕精品免费在线观看视频| 怎么达到女性高潮| 国产激情久久老熟女| 很黄的视频免费| 给我免费播放毛片高清在线观看| 午夜亚洲福利在线播放| 国产黄a三级三级三级人| 免费av毛片视频| 啦啦啦免费观看视频1| 好男人电影高清在线观看| 国产精品亚洲一级av第二区| 中文字幕精品免费在线观看视频| 亚洲精品av麻豆狂野| 国产精品永久免费网站| 老司机午夜福利在线观看视频| 欧美日韩一级在线毛片| 又大又爽又粗| 99国产精品一区二区蜜桃av| 色综合站精品国产| 男女床上黄色一级片免费看| 久久精品aⅴ一区二区三区四区| 欧美又色又爽又黄视频| 12—13女人毛片做爰片一| 麻豆成人av在线观看| 日韩国内少妇激情av| 中文资源天堂在线| 黄色毛片三级朝国网站| 两个人看的免费小视频| 丰满人妻熟妇乱又伦精品不卡| 成年女人毛片免费观看观看9| 非洲黑人性xxxx精品又粗又长| 亚洲色图 男人天堂 中文字幕| 色精品久久人妻99蜜桃| av视频在线观看入口| 91av网站免费观看| 成人亚洲精品一区在线观看| 天堂动漫精品| 草草在线视频免费看| 国产又色又爽无遮挡免费看| 午夜影院日韩av| 午夜福利在线在线| 999精品在线视频| 在线观看www视频免费| 一级a爱视频在线免费观看| 天天一区二区日本电影三级| 国产伦一二天堂av在线观看| 欧美最黄视频在线播放免费| 国产在线精品亚洲第一网站| 制服人妻中文乱码| 国产精品 欧美亚洲| 欧美另类亚洲清纯唯美| 可以免费在线观看a视频的电影网站| 亚洲欧美激情综合另类| 18禁黄网站禁片午夜丰满| 国产精品美女特级片免费视频播放器 | 亚洲av日韩精品久久久久久密| 亚洲熟妇熟女久久| 波多野结衣高清作品| 88av欧美| АⅤ资源中文在线天堂| 亚洲精品美女久久av网站| 亚洲av成人av| 久久久水蜜桃国产精品网| 亚洲av成人av| 国产午夜精品久久久久久| 欧美激情极品国产一区二区三区| 国产亚洲av嫩草精品影院| 男人的好看免费观看在线视频 | 国产黄a三级三级三级人| 国产三级黄色录像| 欧美日韩中文字幕国产精品一区二区三区| 啦啦啦 在线观看视频| 长腿黑丝高跟| 日韩大码丰满熟妇| 日韩欧美国产在线观看| 白带黄色成豆腐渣| 久久人人精品亚洲av| 午夜福利免费观看在线| 国产av又大| 精品第一国产精品| 国产亚洲av高清不卡| 欧美黑人欧美精品刺激| 免费在线观看亚洲国产| 欧美精品啪啪一区二区三区| 两个人免费观看高清视频| 1024香蕉在线观看| 亚洲精品美女久久av网站| 嫩草影院精品99| 叶爱在线成人免费视频播放| 欧美zozozo另类| 免费看十八禁软件| 亚洲五月婷婷丁香| 一进一出抽搐动态| 国产单亲对白刺激| 在线播放国产精品三级| 精品一区二区三区av网在线观看| 亚洲精品av麻豆狂野| 中文资源天堂在线| 老司机在亚洲福利影院| 欧美激情极品国产一区二区三区| 91麻豆av在线| 亚洲一区中文字幕在线| 精品国产一区二区三区四区第35| 午夜亚洲福利在线播放| 97超级碰碰碰精品色视频在线观看| 成人精品一区二区免费| 18禁观看日本| 亚洲中文av在线| 欧美成人性av电影在线观看| 免费女性裸体啪啪无遮挡网站| 免费高清在线观看日韩| 日本 欧美在线| 欧美性猛交╳xxx乱大交人| 成人亚洲精品一区在线观看| 久久天堂一区二区三区四区| 18禁国产床啪视频网站| 成人亚洲精品一区在线观看| cao死你这个sao货| 久久午夜亚洲精品久久| 成年免费大片在线观看| 亚洲欧洲精品一区二区精品久久久| 淫妇啪啪啪对白视频| 韩国av一区二区三区四区| 麻豆成人av在线观看| 自线自在国产av| 日本 av在线| 国产亚洲欧美在线一区二区| 满18在线观看网站| 精品欧美国产一区二区三| 亚洲成国产人片在线观看| 中文字幕最新亚洲高清| 一区二区三区国产精品乱码| 国语自产精品视频在线第100页| 国产高清视频在线播放一区| www日本黄色视频网| 亚洲国产欧洲综合997久久, | 久久伊人香网站| 精品久久久久久久人妻蜜臀av| 老司机在亚洲福利影院| 男人舔女人的私密视频| 国产精品香港三级国产av潘金莲| 国产av不卡久久| 男女视频在线观看网站免费 | 俄罗斯特黄特色一大片| 91国产中文字幕| 精品久久蜜臀av无| 啦啦啦韩国在线观看视频| 欧美激情久久久久久爽电影| 午夜视频精品福利| 日韩欧美一区视频在线观看| 久久久久久国产a免费观看| 中亚洲国语对白在线视频| aaaaa片日本免费| 日本一本二区三区精品| 在线十欧美十亚洲十日本专区| 身体一侧抽搐| 午夜a级毛片| 俄罗斯特黄特色一大片| 真人一进一出gif抽搐免费| 亚洲国产中文字幕在线视频| 久久久久久久久中文| 亚洲五月色婷婷综合| 亚洲精品一区av在线观看| 十八禁网站免费在线| 国产精品一区二区免费欧美| 99热这里只有精品一区 | 在线观看舔阴道视频| 999久久久精品免费观看国产| 日韩 欧美 亚洲 中文字幕| 女性生殖器流出的白浆| a在线观看视频网站| 欧美成人免费av一区二区三区| 欧美久久黑人一区二区| 手机成人av网站| 国产av在哪里看| 国产欧美日韩精品亚洲av| 中亚洲国语对白在线视频| 国产成人欧美在线观看| 一级毛片高清免费大全| 夜夜看夜夜爽夜夜摸| 男女下面进入的视频免费午夜 | 1024视频免费在线观看| 免费看日本二区| 国产成人精品久久二区二区免费| 一区二区三区激情视频| 亚洲精品久久成人aⅴ小说| 黑丝袜美女国产一区| 国产真实乱freesex| 久久热在线av| 侵犯人妻中文字幕一二三四区| 日韩 欧美 亚洲 中文字幕| 国内毛片毛片毛片毛片毛片| 国产成人av教育| 精品国产乱子伦一区二区三区| 少妇 在线观看| 亚洲精品久久成人aⅴ小说| 黄频高清免费视频| 成年免费大片在线观看| 亚洲av片天天在线观看| 天天躁夜夜躁狠狠躁躁| 久久精品影院6| tocl精华| 午夜免费鲁丝| 国产99白浆流出| 亚洲,欧美精品.| 日韩大码丰满熟妇| 国产精品久久电影中文字幕| 女性被躁到高潮视频| 美女大奶头视频| 搡老妇女老女人老熟妇| 国产成人欧美在线观看| 一本综合久久免费| 人人妻人人澡欧美一区二区| 国产精品爽爽va在线观看网站 | 中文字幕av电影在线播放| 国产私拍福利视频在线观看| 成人亚洲精品av一区二区| 99久久久亚洲精品蜜臀av| 大型av网站在线播放| 久久青草综合色| 日韩 欧美 亚洲 中文字幕| 午夜精品久久久久久毛片777| 欧美性长视频在线观看| 国产一区二区三区在线臀色熟女| 亚洲天堂国产精品一区在线| 亚洲精品在线美女| 久久亚洲真实| 欧洲精品卡2卡3卡4卡5卡区| 久热爱精品视频在线9| 91麻豆精品激情在线观看国产| a在线观看视频网站| 精品久久久久久久久久免费视频| 亚洲一区二区三区色噜噜| 天堂√8在线中文| 女警被强在线播放| 亚洲国产日韩欧美精品在线观看 | 国产成+人综合+亚洲专区| 中文字幕人成人乱码亚洲影| 两人在一起打扑克的视频| 18禁观看日本| 一本久久中文字幕| 无限看片的www在线观看| 国产欧美日韩精品亚洲av| 亚洲男人的天堂狠狠| 久久久久久人人人人人| 亚洲黑人精品在线| 99国产精品99久久久久| 宅男免费午夜| 黄色丝袜av网址大全| 黄色 视频免费看| 嫩草影院精品99| 婷婷丁香在线五月| 99国产精品一区二区蜜桃av| 成人国语在线视频| 午夜激情av网站| 美女高潮喷水抽搐中文字幕| 国产精品美女特级片免费视频播放器 | 日本撒尿小便嘘嘘汇集6| 亚洲自偷自拍图片 自拍| 美女大奶头视频| 日韩大码丰满熟妇| 日日摸夜夜添夜夜添小说| 国产三级在线视频| 日韩av在线大香蕉| 精品第一国产精品| 99久久久亚洲精品蜜臀av| 一个人免费在线观看的高清视频| 欧美一级毛片孕妇| 麻豆成人av在线观看| 黄色视频不卡| 亚洲第一欧美日韩一区二区三区| 婷婷精品国产亚洲av| 久久久水蜜桃国产精品网| 性欧美人与动物交配| 白带黄色成豆腐渣| 国产精品久久久久久精品电影 | 757午夜福利合集在线观看| 亚洲成人国产一区在线观看| 久久久国产成人免费| 两性午夜刺激爽爽歪歪视频在线观看 | 国产午夜精品久久久久久| 两人在一起打扑克的视频| 久热爱精品视频在线9| 日韩三级视频一区二区三区| 精品久久蜜臀av无| 亚洲电影在线观看av| 露出奶头的视频| 丰满人妻熟妇乱又伦精品不卡| 悠悠久久av| av视频在线观看入口| 人人澡人人妻人| 亚洲av成人不卡在线观看播放网| cao死你这个sao货| 中文字幕久久专区| 久久狼人影院| 国产熟女午夜一区二区三区| 国产精品亚洲美女久久久| 亚洲成人国产一区在线观看| 无人区码免费观看不卡| 亚洲专区国产一区二区| videosex国产| 丰满人妻熟妇乱又伦精品不卡| 午夜福利高清视频| av超薄肉色丝袜交足视频| 看片在线看免费视频| 国产主播在线观看一区二区| 国产成人av教育| 一二三四在线观看免费中文在| 一个人免费在线观看的高清视频| 久久伊人香网站| 97碰自拍视频| 在线观看免费日韩欧美大片| 欧美乱色亚洲激情| 他把我摸到了高潮在线观看| 成年免费大片在线观看| 亚洲 欧美 日韩 在线 免费| 亚洲精品中文字幕一二三四区| 免费在线观看日本一区| 亚洲国产看品久久| 日韩一卡2卡3卡4卡2021年| 亚洲成人免费电影在线观看| 黄色视频,在线免费观看| 最近最新中文字幕大全电影3 | 18禁国产床啪视频网站| 成人国语在线视频| 亚洲一区二区三区色噜噜| 免费人成视频x8x8入口观看| 中文字幕高清在线视频| 欧美激情 高清一区二区三区| 国产亚洲欧美98| 一进一出抽搐gif免费好疼| a级毛片在线看网站| 欧美乱色亚洲激情| 国产亚洲欧美在线一区二区| 国产片内射在线| 美女午夜性视频免费| 国产成人av教育| 日本成人三级电影网站| 两个人视频免费观看高清| 99国产精品99久久久久| 岛国视频午夜一区免费看| 亚洲国产精品久久男人天堂| 麻豆久久精品国产亚洲av| 国产精品久久视频播放| 欧美精品啪啪一区二区三区| videosex国产| 脱女人内裤的视频| 亚洲激情在线av| 日本三级黄在线观看| www日本黄色视频网| 很黄的视频免费| 欧美一区二区精品小视频在线| 这个男人来自地球电影免费观看| 日本熟妇午夜| av在线天堂中文字幕| 国产激情欧美一区二区| 久久久久久久久久黄片|