稳定同位素标记1,4-二氢吡啶类药剂的5,6-位及其取代基碳的合成

1,4-二氢吡啶结构是许多生物活性物以及药物分子的重要骨架,同时也是非常重要的有机合成中间体。当前并没有一种适用的方法用于¹³C标记1,4-二氢吡啶的合成.提供了一种¹³C标记1,4-二氢吡啶的合成方法以¹³C2-乙酸钠为标记原料,经磷酸酸化得到¹³C2-乙酸,羰基二咪唑酰化¹³C2-乙酸得到¹³C2-N-乙酰咪唑,随后在咪唑钠的作用下进行克莱森缩合反应获得1,2,3,4-¹³C4-乙酰乙酰咪唑的钠盐,经乙酸酸化得到1,2,3,4-¹³C4-乙酰乙酰咪唑,再通过与醇进行酯化得到1,2,3,4-¹³C4-乙酰乙酸酯,1,2,3,4-¹³C4-乙酰乙酸酯经氨基甲酸铵氨化得到1,2,3,4-¹³C4-3-氨基丁烯酸酯。随后采用Hantzsch改进法合成了5,6-位及其取代基碳标记的¹³C4-尼群地平、¹³C4-苯磺酸氨氯地平和¹³C4-马来酸氨氯地平.该方法操作简单,反应条件温和且产率高,为1,4-二氢吡啶的5,6-位及其取代基引入¹³C同位素标记合成提供了新的思路,满足中国仿制药物一致性评价的稳定同位素内标自主合成需求。     

稻秆木素侧链13C同位素示踪及固体13CNMR分析

在水稻(Oryza sativa L.)生长过程中,向其茎秆部节间的空腔分别注入在侧链α,β,γ位带有¹³C标记的松柏醇葡萄糖甙,得到¹³C标记的稻秆木素,用高分辨率固体核磁¹³CNMR对其组织进行分析,发现外源性的松柏醇葡萄糖甙并不影响水稻中木素的正常合成.证明了β-O-4,β-β,β-5和β-1结构是稻秆原本木素中的主要结构,另外还有少量的松柏醇和阿魏酸类结构,并证实木素在α位与糖类等组分有共价键形成.     

The synthesis of [2,3,4-C3]glycitein

Glycitein is one of the soy isoflavones which have attracted considerable interest in recent years due to their possible beneficial effects on human health. However, glycitein has been much less studied than other members of this family due to the lack of good methods for its synthesis. Herein we report a short high yielding synthesis of a multiply ¹³C-labelled glycitein derivative, [2,3,4-¹³C₃]glycitein, which has been employed as an internal standard in LC–MS analysis. A key feature is a rapid and efficient synthesis of 2,4-dihydroxy-5-methoxy-[1′,2′-¹³C₂]acetophenone via acetylation of isovanillin with [¹³C₂]acetyl chloride followed by a Baeyer–Villiger reaction, selective hydrolysis and finally a BF₃ catalysed Fries rearrangement. An aldol reaction using 4-benzyloxy-[carbonyl-¹³C]benzaldehyde gave a chalcone and then thallium(III) mediated oxidative rearrangement, deprotection and cyclisation provided the [2,3,4-¹³C₃]glycitein. The overall yield for the 8 step reaction sequence, based on [¹³C₂]acetyl chloride, was 57%.     

Spectres de rotation de la molécule de chlorobenzéne : I. Variétés isotopiques monosubstituées et structure rs

The microwave spectra of chlorobenzene “(1)-³⁵Cl”, all eight mono-[“(1)-³⁷Cl”, “(1)-³⁵Cl, (2)D”, “(1)-³⁵Cl, (3)D”, “(1)-³⁵Cl, (4)D”, “(1)-³⁵Cl, (1)-¹³C”, “(1)-³⁵Cl, (2)-¹³C”, “(1)-³⁵Cl, (3)-¹³C”, “(1)-³⁵Cl, (4)-¹³C”], one di[“(1)-³⁵Cl, (2,6)D₂,”] and one trisubstituted species [“(1)-³⁷Cl, (2,6)D₂”] have been investigated. From the moments of inertia of the vibrational ground state the r_s structure was derived. The reliability of the two small a coordinates could be enhanced through use of the multiply substituted species. The errors of the moments of inertia were propagated to the structural parameters. It could be shown that the benzene ring is deformed. However the quantitative deformation could not be established due to the rather large errors of some structural parameters.     

Studies in relation to biosynthesis—XXI Rosenonolactone and gibberellic acid

The biosyntheses of rosenonolactone in Trichothecium roseum and of gibberellic acid in Gibberella fujikuroi have been studied by feeding experiments with CH₃¹⁴CO₂Na and (2-¹⁴C)-mevalonic lactone. Preliminary accounts^1–3 of this work have been published.     

An investigation of solute-liquid crystal interaction in hydrogen bonded complexes of palmitic acid and p-octyloxybenzoic acid

The orientational order of a liquid crystalline phase which has a specific solute-liquid crystal interaction was investigated using nuclear magnetic resonance. Three isotopically substituted species of palmitic acid (palmitic acid-d₃₁, 1-¹³C-2.2-H₂-palmitic acid-d₂₉ and 2,2,3,3-H₄-palmitic acid-d₂₇) were dissolved in the liquid crystal p-octyloxybenzoic acid (p-OOBA) and the proton, deuteron and carbon 13 NMR spectra recorded as a function of temperature. ¹H-¹³H dipolar couplings were observed using a spin echo pulse sequence which removes heteronuclear dipolar couplings to the chain deuterons. In the case of the carbon 13 labelled compound, ¹H-¹³C dipolar couplings could be observed by applying an additional refocusing pulse to the ¹³C spins. The dipolar and quadrupolar couplings were used to calculate the complete orientational order matrix of the alpha methylene segment of palmitic acid in p-OOBA. The liquid crystal was shown to largely determine the orientational order of the head group and this was attributed to intermolecular hydrogen bonding. The dipolar and quadrupolar couplings for the rest of the chain were interpreted in terms of a mean field equilibrium statistical model, based on the Samulski Inertial Frame Model. Hydrogen bonding was shown to be of greater importance in the orientational ordering of the solutes in the liquid crystal than are electrostatic interactions in the ordering of the amphiphile in the potassium palmitate/water system.     

Rearrangement studies with C—VIII External and internal returns in the solvolysis of 2-phenyl-1-C-ethyl p-toluenesulfonate

Acetolysis and formolysis of 2-phenyl-1-¹⁴C-ethyl p-toluenesulfonate (I) were interrupted when the reactions were about 50 per cent complete. All samples of 2-phenylethyl p-toluenesulfonate recovered from the partially solvolyzed mixtures showed some rearrangements of the ¹⁴C-labeled atoms from the C-1 to the C-2 positions, indicating the occurrence of some return to covalent bonding through the intermediate ethylphenonium ion (V) or its equivalent. The fraction of V undergoing return as compared to the amount of V involved in product formation was greater for acetolysis than formolysis. The presence of lithium perchlorate gave rise to salt-promoted ionization resulting in an increase in the ¹⁴C rearrangement for the reaction products; however, lithium perchlorate also reduced the relative extent of return involving V. Solvolysis of I in the presence of sodium p-toluene-³⁵S-sulfonate made possible the simultaneous determinations of ¹⁴C rearrangement and ³⁵S exchange in the recovered 2-phenylethyl p-toluenesulfonate. Considerations of such data led to the conclusion that both external and internal returns take place during acetolysis and formolysis of I.     

APPLICATION OF 2D-NMR TECHNIQUES IN THE STRUCTURE DETERMINATION OF HYPODEMATINE

An alkaloid with a novel structure,named Hypodematine,was isolatedfrom Hypodematium sinense Iwatsuki(belonging to Thelypterdaceae).Itsstructure was elucidated by means of the ~1H-~1H COSY' ~1H-~(13)C COSY and long-range~1H-~(13)C COSY spectroscopy to have the skeleton of benzo-aza-cyclooctatetraenewith a phenyl substituent.Such basic structure has not been found in the na-tural product before.     

C and H nuclear magnetic shielding and spin–spin coupling constants of C-enriched bromomethane in the gas phase

¹³C and ¹H NMR spectral parameters are investigated for ¹³CH₃Br in gaseous matrices. It is found that both the ¹³C and ¹H chemical shifts of ¹³CH₃Br are linearly dependent on solvent density. Similar dependence is also detected for one-bond spin–spin coupling, ¹J(CH). For the first time the ¹³C and ¹H magnetic shielding constants and ¹J(CH) spin–spin coupling are obtained for an isolated ¹³CH₃Br molecule together with the coefficients responsible for solute–solvent molecular interactions in gaseous matrices. The present experimental results confirm the accuracy of some recent ab initio calculations of nuclear magnetic shielding performed for bromomethane.     

Direkte und indirekte metallierung von endo-dicylopentadien. Sn- und C-NMR studie stannylierter folgeprodukte

endo-Dicyclopentadiene (1) can be metalated by use of simple procedures with good overall yields. The attack occurs at the various vinyl, rather than at the allyl, positions of 1 as was confirmed by trapping the carbanions with Me₃SnCl. When t-BuLi/TMEDA are used, the 8- and 9-stannyl derivatives (3 and 4) are formed, whereas an excess of n-BuLi/t-BuOK leads to doubly stannylated derivatives with Me₃Sn groups in position 4/8 (6), 4/9 (7), and 3/9 (8) in addition to 3 and 4. Furthermore the latter reaction yields 5,5-bis(trimethylstannyl)cyclopentadiene (5). With stoichiometric amounts of n-BuLi/t-BuOK the formation of 3 and 4 predominates over that of 5–8. 5 is obtained from 1 after deprotonation at the allyl position, followed by an extremely fast retro-Diels-Alder reaction and then by further deprotonation. This follows from two experiments: (1) exo- and endo-5-trimethylstannyl-endo-dicyclopentadiene (11 and 12) which are synthesized from 1 in three steps give cyclopentadienyllithium and 1 when treated with methyllithium at −78°C; (2) cyclopentadiene reacts with an excess of n-BuLi/t-BuOK and Me₃SnCl to give 5. When 12 is heated syn-10-trimethylstannyl-endo-dicyclopentadiene (13) is obtained. The eight stannyl derivatives of 1 are identified mainly from the following NMR parameters: δ(¹¹⁹Sn), δ(¹³C), δ(¹H), ⁿJ(^119/117Sn---¹³C), and ⁶J(¹¹⁹Sn---^119/117Sn). The ¹³C NMR satellite spectrum of 1 yields the isotope shifts ¹Δ¹³(i(¹³C(j)) and ¹J(¹³C---¹³C). The latter lead to the revision of earlier signal assignments.     

B环对位取代异黄酮化合物的核磁共振研究

对14个合成的B环对位取代异黄酮化合物核磁共振氢谱进行了研究.利用超导核磁共振归属了B环无取代异黄酮质子的化学位移,根据取代基化学位移的变化影响规律考察了取代基对分子的影响方式.研究结果表明,2'(6'),3'(5')位质子共振迁移分别与取代基参数σ_p和S_o线性相关,说明4'位取代基主要通过电子效应影响其间位质子,其磁各向异性仅影响邻位质子,该取代基对A环质子影响不大,而对C环尤其是对2-H影响较明显.     

几种咔唑衍生物(有机光导材料)的13C核磁共振谱的研究

我们测定了3-溴咔唑,3,6二溴咔唑,9-(2',3'-环氧丙基)咔唑,9-(2',3'-环氧丙基)-3-溴咔唑和9-(2',3'-环氧丙基)-3,6-二溴咔唑(后分别简称化合物1,2,3,4,5)的宽带去偶谱、偏共振谱和非去偶谱。通过对它们的¹³C核磁共振谱的数据分析比较,就以下几方面进行了归纳总结:①信号的归属方法;②环氧丙基的¹³C化学位移范围;③偶合常数的范围,这些归纳总结有助于确定此类化合物的价键特征和结构。     

酞侧基聚芳醚酮的核磁共振研究(Ⅰ)──链结构及NMR谱的归属

用1D NMR方法研究酞侧基聚芳醚酮(PEK-C)链结构,用二维同核化学位移相关与二维异核化学位移相关实验方法对1D NMR谱峰进行归属,探讨了二维异核远程相关实验在缩聚高分子研究中的应用,为PEK-C修饰机理以及共混相容机理的研究提供重要信息。溶液NMR谱图数据表明,PEK-C具有较规整的链结构。     

The complete assignment of the h and C nmr spectra of the alkali metal salts of salinomycin and narasin

The preparation of the alkali metal salts of salinomycin and narasin, apart from lithium narasin, is described. The complete assignment of their ¹H spectra based on two dimensional COSY and NOESY spectra is reported. These asignments are then used in two dimensional ¹³C/¹H correlations via direct and long range couplings to assign the ¹³C spectra. Assignments in the ¹³C spectrum of sodium salinomycin differ in important details from those in a previous report.     

H, C NMR spectral and single crystal structural studies of toxaphene congeners. Quantum chemical calculations for preferred conformers of 2,5-endo,6-exo,8,9,9,10,10-octachloro-2-bornene and their DFT/GIAO C chemical shifts

The ¹H and ¹³C NMR chemical shifts for six toxaphene congeners: 2-exo,3-endo,6-exo,8,9,10-hexachloro- (1), 2-exo,3-endo,5-exo,9,9,10,10-heptachloro- (2), 2-exo,3-endo,6-exo,8,9,10,10-heptachloro- (3), 2-exo,3-endo,5-exo,6-endo,8,9,10-heptachloro- (4), 2-exo,3-endo,5-exo,6-endo,8,9,9,10-octachlorobornane (5) and 2,5-endo,6-exo,8,9,9,10,10-octachloro-2-bornene (6) are reported. Their chemical shift assignments have been obtained by means of Pulsed Field Gradient (PFG) Double Quantum Filtered (DQF) ¹H,¹H correlation spectroscopy (COSY), PFG ¹H,¹³C Heteronuclear Multiple Quantum Coherence (HMQC) and PFG ¹H,¹³C Heteronuclear Multiple Bond Correlation (HMBC) experiments. A single crystal X-ray structural analysis was made for compounds 1, 3, 4 and 6. The prevalences of two octachlorobornene rotamers (6a,6b) were elucidated by ab initio MO method and single point DFT/GIAO calculations for ¹³C chemical shifts. Theoretical calculations proved that the single crystal structure of 6 corresponds its most stable conformer in solution.     

Hydrogen-bonding effect on C NMR chemical shifts of amino acid residue carbonyl carbons of some peptides in the crystalline state

¹³C cross polarization-magic angle spinning NMR spectra were measured for a series of peptides containing -valine, -leucine and -aspartic acid residues, for which the crystal structures were already determined by X-ray diffraction, in order to investigate the relationship between hydrogen-bond lengths (R_N…O) and ¹³C chemical shifts of amide carbonyl carbons in the peptides. From these experimental results, it was found that the isotropic ¹³C chemical shifts (δ_iso) of the amino acid residues move linearly downfield with a decrease in R_N…O within the hydrogen-bonded length range considered here and also shown in our previous work on glycine and -alanine residues as expressed by δ_iso(ppm) = a − bR_N…O(Å) where a and b are 215.4 (ppm) and 14.2 (ppm Å⁻¹) for the -valine residue, 202.2 (ppm) and 10.0 (ppm Å⁻¹) for the -leucine residue, and 199.0 (ppm) and 9.6 (ppm Å⁻¹) for the -aspartic acid residue, respectively. Using these relations, the R_N…O values of some polypeptides in the crystalline state were determined through the observation of the amide carbonyl carbon chemical shifts. These values were compared with those determined by the X-ray diffraction method. Furthermore, quantum-chemical calculation of the ¹³C shielding constant for a model compound was carried out by the finite perturbation theory INDO method in order to ascertain the ¹³C shielding behavior in the formation of hydrogen bonds.     

Sn-Al-β分子筛酸性在葡萄糖转化反应中作用的固体NMR研究

制备了一系列具有不同酸性质的β分子筛催化剂, 通过固体核磁共振(NMR)探针分子技术对其酸性质进行了表征, 并考察了其催化葡萄糖转化为乙酰丙酸甲酯的性能. 吸附三甲基磷的³¹P NMR实验结果表明, 含有骨架Sn以及Al原子的Sn-Al-β催化剂同时具有Br?nsted与Lewis酸性. 通过2-¹³C-丙酮探针分子区分出 3种酸强度的Br?nsted酸位, 其中一种酸强度接近“超强酸”, 可能是由于空间邻近的Br?nsted酸位和Lewis酸位发生协同作用产生的. 葡萄糖转化为乙酰丙酸甲酯的催化反应结果表明, 相比于分别只含有Lewis酸位和Br?nsted酸位的Sn-β和Al-β样品以及两者的物理混合样品, Sn-Al-β分子筛催化剂具有高催化活性与产物选择性, 这主要是由于Br?nsted酸位和Lewis酸位的协同作用产生了强Br?nsted酸位, 这种强Br?nsted酸位进一步导致了更高的催化活性.     

Synthese et etude par resonance magnetique nucleaire de complexes olefiniques de l''iridium et du rhodium avec quelques bases de schiff derivees de l''aldehyde salicylique

[M(bds)(cod)] compounds (M = Ir or Rh, cod = 1,5-cyclooctadiene, bds = Schiff's base) have been studied by ¹H and ¹³C NMR.

Signals corresponding to the atoms of the double bond trans to the oxygen atom appear at higher field than those of the trans nitrogen side. ¹ and ¹³C attributions have been related by selective decoupling. Some structural data have been also obtained.     

Smenoqualone a novel sesquiterpenoid from the marine sponge Smenospongia sp.

Smenoqualone, a novel quinonic terpenoid with a rearranged drimane skeleton was isolated from a marine sponge Smenospongia sp. The stereostructure was determined by detailed analyses of ¹H and ¹³C NMR spectra, ¹H-¹H COSY, ¹H-¹³C correlations via HMQC, HMBC and NOE difference NMR experiments.     

Synthesis and Biological Evaluation of Novel Saccharin Derivatives Containing 1,2,3-Triazole Moiety

A series of novel saccharin derivatives containing 1,2,3-triazole moiety was synthesized in satisfactory yields. The structures of all the compounds were elucidated and confirmed by Fourier transform infrared(FTIR) spectroscopy, ¹H and ¹³C nuclear magnetic resonance(¹H NMR, ¹³C NMR) spectroscopy, and high resolution mass spectrometry(HRMS). The bioassays indicated that most of the title compounds displayed some extent herbicidal activities at 100 μg/mL.