2015年药学大会暨第十五届药师

a，a，a，a，b（a大学人民医院药学部；b华技大学同济医学院药学院：本文对照山白花的化学成分进行了系统研究。通过反复硅胶、ODS以及Sephadexmenthiafolicacid(p-menthane-1,2,8-triol-2-O-β-D-glucopyranoside(2),deacetylasperuloside(3),6,7-dihydromonotropein4monotropeine5)adoxosidicacid6)。所得化合物均为首次从该照山白为花科花属植物（RhododendronmicranthumTurcz.，分布于1个二萜[2]、5个三萜[3]7个黄酮[45]。对照山白花中化学成分的研究尚无文95%6menthiafolicacid(1)[6],p-menthane-1,2,8-triol-2-O-β-D-glucopyranoside(2)[7],deacetylasperuloside3)[86,7-dihydromonotropein(4)[9],monotropeine(5)[10]adoxosidicacid(6)[10]。核磁仪[BrukerAv-400spectrometer，以氘代试剂中残留的质子信号为内标：CD3OD(δH3.31,δC49.15),DMSO-d6(δH2.50,δC39.51)]；日立高效液相色谱仪（UV-C-mm5µmSephadex（PharmaciaBioteck，ODS（50µm，YMC公司（200~300目，化学纯，青和水溶性部分160g。水溶性部分（160g）经正相硅色谱以氯仿-甲醇（20:1~1:1）梯度（A~J1（3.0mg10:12（4.4mg（20.1mg，4（6.9mg（85.6mg甲醇5:1）和反相硅色谱（10%甲醇）得到化合物6（13.0mg。D化合物(1):无色油状物D

+2(c0.3,CHCl3);1HNMR(CDC13,400MHz)1.30(3H,s,H-10),1.64(2H,m,H-5),1.81(3H,s,H-9),2.25(2H,m,H-4),5.08dd,J=10.8,1.0Hz,H-8a),5.22(1H,dd,J=17.4,1.00Hz,H-8b),5.89(1H,dd,J17.4,10.8Hz,H-7),6.87(1H,dd,J=6.2,7.5Hz,H-3).13CNMR(CDCl3,δ:12.2(C-9),23.9(C-4),28.3(C-10),40.7(C-5),73.3(C-6),112.5(C-8),(C-2),144.6(C-3),145.0(C-7),172.9(C-l).以上数据与文献基本一致[6]，故鉴定1menthiafolicacidD化合物(2):白色无定型粉末;[α]20+9(c0.2,MeOH);1HNMR(CD3OD,DMHz)δ:1.11(3H,s,H-7),1.26(3H,s,H-10),1.31(3H,s,H-9),1.41(1H,m,H-1.53(1H,m,H-4),1.55(1H,m,H-6a),1.73(1H,m,H-6b),1.92(1H,m,H-3a),(1H,m,H-5b),2.11(1H,m,H-3b),3.20(1H,dd,J=9.0,7.8Hz,H-2′),3.25(1H,H-4′),3.26(1H,m,H-5′),3.36(1H,m,H-3′),3.64(1H,dd,J=11.9,5.7Hz,H-3.86(1H,dd,J=11.9,2.2Hz,H-6′b),3.90(1H,dd,J=9.3,3.1Hz,H-2),4.37(1H,J=7.8Hz,H-1′).13CNMR(CD3OD,100MHz)δ:74.1(C-1),75.1(C-2),31.8(C-34.9(C-4),22.9(C-5),31.2(C-6),23.7(C-7),75.9(C-8),28.5(C-9),29.4(C-100.7(C-1′),75.1(C-2′),78.3(C-3′),72.1(C-4′78.2(C-5′),63.2(C-6′).[7]2为p-menthane-1,2,8-triol-2-O-β-D-D化合物(3):白色无定型粉末;[α]20–128(c0.4,MeOH);1HNMR(D400MHz)δ:3.92(1H,dd,J=11.9,1.9Hz,H-6′a),4.17(1H,d,J=16.0Hz,H-4.21(1H,d,J=16.0Hz,H-10b),4.68(1H,d,J=7.9Hz,H-1′),5.56(1H,d,J=Hz,H-6),5.64(1H,brs,H-7),5.95(1H,brs,H-1),7.29(1H,d,J=2.0Hz,H-3).NMR(CD3OD,100MHz)δ:93.4(C-1),150.4(C-3),106.6(C-4),37.6(C-5),(C-6),125.8(C-7),150.0(C-8),45.1(C-9),60.2(C-10),173.0(C-11),100.0(C-74.8(C-2′),78.6(C-3′),71.7(C-4′),78.0(C-5′),62.9(C-6′).以上数据与文献基一致[8]3deacetylasperulosideD化合物(4):白色无定型粉末;[α]20–197(c0.2,MeOH);1HNMR(D400MHz)δ:1.64(1H,m,H-6α),1.65(1H,m,H-7α),1.74(1H,m,H-7β),2.12td,J=10.2,3.3Hz,H-6β),2.26(1H,dd,J=9.0,5.8Hz,H-9),2.85(1H,dd,J=7.5Hz,H-5),3.23(1H,m,H-4′),3.50(2H,s,H-10),3.68(1H,dd,J=11.9,4.7H-6′a),3.86(1H,d,J=11.9Hz,H-6′b),4.73(1H,d,J=7.9Hz,H-1′),5.43(1H,d,=5.7Hz,H-1),7.48(1H,s,H-3).13CNMR(CD3OD,100MHz)δ:96.5(C-1),153.4(C-3),112.7(C-4),35.9(C-5),31.9(C-6),36.9(C-7),83.5(C-8),46.3(C-9),(C-10),171.1(C-11),100.9(C-1′),74.8(C-2′),78.5(C-3′),71.4(C-4′),78.0(C-[9]D化合物(5):whiteamorphouspowder;[α]20–135(c0.1,MeOH);1HD(DMSO-d6,400MHz)δ:2.55(1H,d,J=9.1Hz,H-9),2.95(1H,m,H-2′),3.04m,H-4′),3.44(1H,overlap,H-6′a),3.68(1H,dd,J=10.4,6.0Hz,H-6′b),4.43d,J=7.9Hz,H-1′),5.52(1H,brs,H-1),5.53(1H,dd,J=5.6,1.3Hz,H-7),(1H,dd,J=5.6,2.7Hz,H-6),7.23(1H,d,J=0.8Hz,H-3).13CNMR(DMSO-100MHz)δ:92.5(C-1),150.1(C-3),109.1(C-4),36.7(C-5),134.9(C-6),(C-7),83.9(C-8),42.9(C-9),66.3(C-10),167.9(C-11),98.1(C-1′),73.0(C-2′),(C-3′),70.0(C-4′),76.8(C-5′),61.1(C-6′).以上数据与文献基本一致[10]，故鉴定化5monotropeine。D化合物(6):whiteamorphouspowder;[α]20–127(c0.2,MeOH);1HD(CD3OD,400MHz)δ:1.37(1H,m,H-6α),1.45(1H,m,H-7α),1.83(1H,m,H-2.16(1H,m,H-6β),1.94(1H,dd,J=12.9,7.0Hz,H-9),2.81(1H,q,J=7.5H-5),3.52(1H,m,H-10a),3.57(1H,m,H-10b),3.68(1H,dd,J=11.9,4.7H-6′a),3.86(1H,d,J=11.9,2.6Hz,H-6′b),4.67(1H,d,J=7.9Hz,H-1′),5.18d,J=5.7Hz,H-1),7.47(1H,s,H-3).13CNMR(CD3OD,100MHz)δ:98.6(C-153.4(C-3),112.5(C-4),36.6(C-5),33.6(C-6),28.8(C-7),44.4(C-8),44.4(C-66.8(C-10),171.6(C-11),100.6(C-1′),74.9(C-2′),78.4(C-3′),71.7(C-4′),[10]95%6个 江苏新医学院.中药大辞典[M].:科技,1986: ，，叶孔谟，等.照白除毒生产工艺的研究[J].沈阳药学院学报,1978,1(9):常国栋，罗都强.照山白的化学成分研究[J].亚太传统,2011,7(4):夏重道，杜安全，王红萍，等.照山白有效成分的化学研究[J].中国药学学报,1999,30(4):314–315.杨秀岭袁志芳许慧君等.照山白黄酮类化学成分的研究[J].药物分析,2010,Arslanian,R.L.;Anderson,T.;Stermitz,F.R.IridglucosidesofPenstemonambiguus.J.Nat.Prod.1990,53(6),1485–1489.Ishikawa,T.;Kudo,M.;Kitajima,J.Water-solubleconstituentsofDill.Chem.Pharm.Bull.50(4),Otsuka,H.;Yoshimura,K.;Yamasaki,K.;Cantoria,M.C.Isolationof10-O-acyliridglucosidesfromaPhilippinemedicinalnt,OldenlandiacorymbosaL.(Rubiaceae).Chem.Pharm.Bull.1991,39(8),2049–2052.Taskova,R.M.;Gotfredsen,C.H.;Jensen,S.R.ChemotaxonomyofVeroniceaeanditsalliesinthentaginaceae.Phytochemistry2006,67,286–301.Jensen,H.D.;Krogfelt,K.A.;Cornett,C.;Hansen,