外消旋体的HPLC拆分

前言化合物的生物活性往往由它们的立体选择性所决定。手性物质可能具有显然不同的生理活性或强度。所以某个光学异构体(对映异构体)呈现某种所需要的疗效,而另外一构型能引起相反的作用,甚至毒性。如反应停,只有R-(+)-构型具有催眠作用,而S-(一)-构型致畸。心得安的光学异构体呈现不同的效价,S-异构体作用要比R-构型强100倍。人体内也存在着许多具有不对称中心结构的化合物。于是出现了两种构型,它们互为镜像。这些光学异构体中,通常只有一种构     

3S-(2R-2-苯基-2-环戊基-2-羟基乙氧基)奎宁环烷的晶体结构

选择性抗胆碱药3-(2-苯基-2-环戊基-2-羟基乙氧基)奎宁环烷盐酸盐的分子结构中有两个手性碳原子,其中奎宁环3位的手性碳绝对构型已知。本文报道用X衍射技术,测定了其中一个光学异构体(S-1)的碘甲烷季铵盐的分子结构,确定了另外一个手性碳的绝对构型。该化合物命名为:S-(2R-2-苯基-2-环戈基-2-羟基-乙氧基)-奎宁环烷。     

牛膝甾酮25位差向异构体的分离与鉴定

目的分离并确定苋科植物怀牛膝(Achyranthes bidentata Blume.)中牛膝甾酮25位差向异构体的结构。方法利用色谱技术分离纯化牛膝甾酮25位差向异构体，用波谱(IR,UV,MS,NMR)方法及化学方法确定结构。结果从怀牛膝的乙酸乙酯部位分离得到3个化合物，分别鉴定为25S-牛膝甾酮(1, 25S-inokosterone)，25R-牛膝甾酮(2, 25R-inokosterone)，β-蜕皮甾酮(3, ecdysterone)。结论化合物1和2为首次从怀牛膝中分离得到的25位差向异构体，首次确定了25位绝对构型和发表该25位差向异构体的¹³CNMR数据。     

白花前胡中前胡香豆素D和前胡香豆素E的分离和鉴定

从中药白花前胡(Peucedanum Praeruptorum Dunn)根中分到5个化合物,经理化常数、波谱数据及化学反应分别鉴定为前胡香豆素D(I),Pd-Ib(II),前胡香豆素E(III),nodakenetin(IV)和scopoletin(V)。其中化合物I和III为两个新化合物,与巳知化合物凯林内酯的化学沟通确定了其绝对构型,其化学结构分别为3'(S),4'(S)-二乙酰氧基-3',4'-二氢邪蒿内酯(I)和3'(R)-惕各酰氧基-4'-酮基-3',4'-二氢邪蒿内酯(III)。化合物IV和V为首次从该植物中分离得到。通过DEPT,¹H-¹HCOSY和¹³C-¹HCOSY等实验归属了II的碳氢信号。     

新型抗胆碱能药物盐酸戊乙奎醚及其光学异构体的细胞毒性评价

目的:评价新型抗胆碱能药物盐酸戊乙奎醚(PHC)及其4个光学异构体R-1、R-2、S-1和S-2的细胞毒性。方法:不同浓度的PHC及其光学异构体作用HepG2细胞24 h后,采用MTT法和中性红吸收法测定细胞毒性:结果:PHC及其光学异构体均能浓度依赖性地降低细胞存活率。根据半数抑制浓度(IC_(50))比较这5个抗胆碱能化合物的细胞毒性:MTT法所测定的细胞毒性强弱次序为PHC>R-2>R-1>S-2>S-1,中性红吸收法所测定的细胞毒性强弱次序为R-2>PHC≈R-1>S-2>S-1。结论:就HepG2细胞而言,R构型异构体的细胞毒性强于S构型。并且,在PHC的4个光学异构体中,R-2的细胞毒性相对最强,而S-1相对最弱。     

FAB-MS/MS法研究4(20)-双键5/7/6型紫杉烷类二萜化合物的质谱裂解特征

目的　研究4(20)-双键5/7/6型紫杉烷类二萜化合物的质谱裂解特征,以及取代基种类及位置对质谱裂解的影响,探讨该类化合物的质谱裂解规律。方法　利用FAB技术测定该类型3种化合物的［M+H］⁺和［M+Na］⁺等不同加合离子,以及由其产生的特征碎片离子的CID-MS/MS谱,并对有关特征离子进行了高分辨测定。结果　C-10位为BzO取代的化合物1和2主要以［M+Na］⁺离子形式存在,该离子主要进行失去HOBz的裂解反应,而C-10位为OH基的化合物3主要以［M+H］⁺离子形式存在,该离子以失去1个和2个H₂O的裂解反应为主导。另外,化合物1和3最终裂解产生m/z 237离子,而化合物2产生m/z 253离子。结论　MS/MS技术可以有效地进行结构差异甚微的相关化合物的结构解析。     

新型四氢-2-萘醇类化合物的合成、晶体结构及抗肿瘤活性

目的：合成（E）-6-甲氧基-1-（3,4,5-三甲氧基苯亚甲基）-1,2,3,4-四氢-2-萘醇及其对映异构体,测定其晶体结构,并考察其生物活性。方法以2,6-二甲氧基萘为起始原料,经还原及Knoevenael 缩合制得中间体萘酮,再以CBS不对称催化还原分别制得R、S构型的目标化合物。采用单晶X-衍射测定其晶体结构,并测试其微管蛋白的抑制活性及体外抗肿瘤活性。结果目标化合物结构经MS、NMR及X-单晶衍射等确证。目标化合物的不对称还原反应收率达90．3％,e．e．％达99．04％,体外药理活性数据显示,S-构型目标化合物对微管蛋白聚合、HCT116和CCRF-CEM肿瘤细胞的抑制活性优于R-构型异构体及先导化合物22b,其IC50分别达到0．41、0．14和0．001μmol/L。结论采用CBS不对称催化还原的方法是一条制备高光学纯度的手性目标化合物的合成方法;高活性的S构型异构体具有进一步研究的价值。     

牛膝中牛膝甾酮25位异构体构型的确定及其抗肿瘤活性的研究

目的牛膝 (AchyranthesbidentataBl.)中牛膝甾酮 2 5位异构体的分离、鉴定、构型确定以及肿瘤抑制活性的测定。方法利用硅胶吸附柱色谱和HPLC法进行分离 ,利用理化性质和波谱分析对化合物进行鉴定 ;利用体外实验法测定其活性。结果 2个非对映异构体化合物分别鉴定为 2 5 R牛膝甾酮 (2 5 Rinokosterone ,1)和 2 5 S牛膝甾酮 (2 5 Sinokosteone ,2 )。化合物 1具有一定的肿瘤抑制活性。结论 2个化合物均为首次从牛膝中分离得到 ,首次确定了其绝对构型 ,并首次对牛膝甾酮 2个 2 5位异构体进行了1H NMR、13 C NMR数据归属。牛膝中发挥肿瘤抑制作用的成分主要应为皂苷类成分。     

鸟嘌呤核苷-3′,5′-环磷酸衍生物的合成及生物活性研究

本文报道用三价磷试剂与保护的鸟嘌呤核苷反应,经碘氧化生成鸟嘌呤核苷-3′,5′-环磷酸酯和磷酰胺,并对它们的生物活性做了初步研究,N²-二甲胺基甲烯基-2′-叔丁基二甲基硅基鸟嘌呤核苷-3′,5′-环磷酸酯和磷酰胺对小鼠肝癌腹水细胞的DNA和RNA合成有一定的抑制作用。N²-二甲胺基甲烯基鸟嘌呤核苷-3′,5′’-环磷酸丁酯的两个磷原子构型不同的异构体可激活腺苷酸环化酶,使大鼠成骨肉瘸细胞株ROS 17/2.8的cAMP水平增高。     

HM-PAO非对映立体异构体的核磁共振鉴定及立体异构纯度的测定

本文报道外消旋和内消旋六甲基丙二胺肟(HM-PAO)在一些常见溶剂中的¹H和¹³C化学位移。利用它们的¹³CNMR谱或氯仿中的¹HNMR谱,可以方便地鉴定这两个性质非常近似的非对映立体异构体。研究结果还表明,利用常规的全去偶¹³CNMR谱可以测定外消旋体在这两种异构体混合物中的立体异构纯度。     

贝母辛的结构修正

从川产家种华西贝母(Fritillaria siechuanica)鳞茎中分出贝母辛(peimisine)(碱Ⅲ)。应用光谱法(¹H—¹H,¹³C—¹H COSY,2D—NOE),对文献报告的贝母辛的结构作了修正,并证明FR—5与贝母辛系同一化合物。指出湖贝辛结构的某些错误以及对松贝辛的结构提出怀疑,认为其可能为贝母辛。     

远程二维核磁共振和NOE差谱法研究新生物碱马尾杉碱N的结构

自华南马尾杉[Phlegariurus fordii(Baker)Ching]中分得新生物碱—马尾杉碱N(Ⅰ)。它含有七个季碳。本工作采用远程¹³C—¹HCOSY和远程增强型¹H—¹HCOSY新技术与NOE差谱相配合的方法成功地连接被季碳和杂原子分隔开的自旋系统,推定了其结构。     

用二维核磁共振技术研究赤芝孢子内酯A和B的结构

通过~1H-~1H,~1H-~(13)C相关谱(COSY),~1H-~(13)C远程偶合相关谱(OOLOC)及NOE二维谱(NOESY)等新的二维核磁共振技术确定了两个新化合物赤芝孢子内酯A和B的结构。     

头孢菌素类抗生素的核磁共振波谱特征

目的阐述头孢菌素类抗生素的核磁共振波谱特征。方法应用1H-1H COSY、HMQC,HMBC等二维核磁共振技术对头孢噻吩钠等8个头孢菌素类抗生素进行了测试。结果在对8个头孢菌素类抗生素的1H NMR1、3C NMR信号进行全归属的基础上,对1H NMR谱偶合裂分、偶合常数及1H NMR1、3C NMR谱中取代基对化学位移的影响进行了分析,总结了头孢菌素类抗生素核磁共振波谱的特征。结论头孢菌素类抗生素母核的1H NMR和13C NMR谱有明显特征,取代基的变化对质子和碳的化学位移影响有一定规律。     

鲜罗汉果中黄酮甙的分离及结构测定

A new flavonol glycoside named grosvenorine and a known compoundwere isolated from the fresh fruits of Siraitia grosvenori( swingle)C. By means of UV,FAB-MS,¹H-¹H COSY,¹³C-1H COSY and NOE difference ,spectra,the structure of grosvenorinewas established as kaempferol-3-O-α-L-rhafmnopyranoside-7-O[β-D-glucopyranosyl-(1-2)-α-L-rhamnopyranoside].The known compound was identified as kaempferol-3,7-α-L-dirhamnopyra-noside.     

NMR studies of an oligonucleotide with an unusual structure induced by platinum anti-cancer drugs

The 31P NMR spectra of Pt(en)[d(T1A2T3G4G5G6T7A8C9C10C11A12T13A14)] (14-mer) and Pt(en)[d(A2T3G4G5G6T7A8C9C10C11A12T13)] (12-mer) (en = ethylenediamine) each contain two signals far downfield (ca. -2.9 and -2.6 ppm from trimethylphosphate standard), two signals slightly downfield, and at least one signal slightly upfield of the normal range (ca -4.0 to -4.4 ppm). This pattern suggested a distorted structure. The unusual 31P signals of the 12-mer were assigned by analogy to signals of the 14-mer previously assigned by 17O-labeling methods. A combination of heteronuclear multiple-quantum coherence, one-dimensional and two-dimensional nuclear Overhauser effect (1D and 2D-NOE) and homonuclear shift correlation spectroscopy (COSY) experiments assigned all aromatic 1H signals of the 12-mer except H8 of G5 or G6. One of these H8 signals is missing from the spectrum and the nucleotide is labeled Gm. The other H8 is the most downfield signal and has a strong NOE to its H1'. Since this strong NOE indicates that this nucleoside exists in a syn conformation, it is labeled Gs. A strong NOE was observed between the Gs and A8 H8 signals. Several lines of evidence suggested a hairpin-like structure with a loop region (G6T7A8C9) and a stem region involving A2T3G4G5 and C10C11A12T13. The 31P signals for the stem region are within or slightly outside the normal range. 3JH3'-P values (3-6 Hz), measured by a 2D-J experiment, of stem nucleotides were characteristic for a DNA duplex. Imino signals for base pairs A2T13, T3A12, G4C11, and probably G5C10, and the observation of internucleotide NOE connectivities for these nucleotides (e.g. between an H8 signal and the H1' signal of the 5' nucleotide) suggested a right-handed helical structure. For the loop region, a distorted sugar-phosphate backbone is indicated by far downfield positions of the G5pG6 and A8pC9 31P signals, the 3JH3'-P values for C9p (8.0 Hz) and A8p (6.8 Hz), and the absence of H3'-P coupling for G5p. In the loop region, no imino signals or internucleotide NOEs characteristic of a right-handed duplex were observed. However, A8H8, C9H6, and C10H6 each exhibited unusual internucleotide NOEs to the H4' signal of the 5' residue. NOE crosspeaks between T7 1H signals and signals attributed to sugars of the Gs and Gm suggested that the T7 moiety is located within the space encircled by the loop. The few NOE crosspeaks, pH dependence, and Cu2+ broadening of C9 1H signals indicate an isolated location accessible to solvent.(ABSTRACT TRUNCATED AT 400 WORDS)     

文冠木中五种黄酮类成分的NMR研究

应用~1H—~(13)C co(?)y,~1H—~(13)C long(?)ange cosy等二维核磁共振技术,对文冠木中具有血小板聚集抑制活性的5种黄酮类成分的~1H—及~(13)C—NMR信号做了明确归属。     

Zelkovamycin, a new cyclic peptide antibiotic from Streptomyces sp. K96-0670. II. Structure elucidation

The structure of antibiotic zelkovamycin was elucidated as a cyclic peptide comprising glycyl, 2-aminobutanoyl, 2-amino-2-butenoyl, N-methyl glycyl, alanyl, 1,3-thiazoyl, 7-methoxytryptophanyl and 2-methyldehydrothreonyl residues. The sequence of the amino acids was established by spectroscopic studies including 1H-1H COSY, 13C-1H COSY, 13C-1H HMQC, 13C-1H HMBC, 15N-1H HMQC and 15N-1H HMBC NMR experiments.     

New steroidal saponins from Agave lophantha Schiede and their pharmacological evaluation

The structures of one new monodesmosidic spirostanoside and one new bisdesmosidic furanostanol glycoside isolated from leaves of Agave lophantha Schiede have been determined by means of spectroscopic and chemical methods as (25R)-5 beta-spirostan-3 beta-ol-3-O-(beta-D-apiofuranosyl(1-->4)beta-D -glucopyranosyl(1-->3)[beta-D-glucopyranosyl(1-->2)]beta-D -galactopyranoside) and 26-O-beta-D-glucopyranosyl(25R)-5 beta-furost-20(22)-ene-3 beta, 26-diol-3-O-(beta-D-xylopyranosyl(1-->3)-[beta-D-glucopyranosyl(1--2)] beta-D-galactopyranoside), respectively. The 1H and 13C NMR resonances of the two compounds were assigned by NMR (1H, 13C, HOHAHA, 1H-1H COSY, HMQC, HMBC, NOE difference) studies. The pharmacological activities of the saponin containing fraction are discussed.     

Epiderstatin, a new inhibitor of the mitogenic activity induced by epidermal growth factor. II. Structure elucidation

The structure of a novel antibiotic, epiderstatin, was determined as 4-[3-((Z)-3,5-dimethyl-2-oxopiperidin-6-ylidene)-2-oxopropyl]-2, 6-piperidinedione by spectroscopic analyses of 1H NMR, 13C NMR, 1H-1H correlation spectroscopy (COSY), 13C-1H COSY, heteronuclear multiple bond correlation spectroscopy, UV and IR spectra. The antibiotic belongs to the glutarimide antibiotics, however, the characteristic feature of epiderstatin is that it has a piperidone ring instead of a cyclohexanone ring.