云南蕊木茎中的抗炎吲哚生物碱

应用多种色谱和波谱学方法,从云南蕊木(Kopsia officinalis)茎中分离鉴定了27个单萜吲哚生物碱,包括7个新化合物kopsiofficines A～G和20个已知化合物.此外,建立脂多糖(LPS)诱导的小鼠巨噬细胞RAW 264.7炎症模型,通过测定IL-1β, PGE2和TNF-α炎症因子释放评价生物碱的抗炎活性.结果表明, kopsiofficines A (1), kopsiofficines B (2),kopsiofficines D(4),kopsiofficines F(6),kopsiofficines G(7), 12-methoxykopsine(11),kopsinoline(15),(-)-N-methoxy-carbonyl-11,12-methylenedioxykopsinaline(16),kopsinine(18)和kopsinic acid(20)表现出显著的抗炎活性,与阳性对照(地塞米松)基本相当.研究发现C-5位丙酮基取代的单萜吲哚生物碱的抗炎活性明显强于原型生物碱,推测丙酮基可能是抗炎活性的药效促进基团,研究结果为进一步的结构修饰...     

Chemical fingerprint and simultaneous determination of alkaloids and flavonoids in aerial parts of genus Peganum indigenous to China based on HPLC‐UV: application of analysis on secondary metabolites accumulation

The aerial parts of genus Peganum are officially used in traditional Chinese medicine. The paper aims to establish a high‐performance liquid chromatography (HPLC) method for fingerprint analysis and simultaneous determination of three alkaloids and two flavonoids in aerial parts of genus Peganum, and to analyze accumulative difference of secondary metabolites in inter‐species, individuals of plants, inter‐/intra‐population and from different growing seasons. HPLC analysis was performed on a C₁₈ column with gradient elution using 0.1% trifloroacetic acid and acetonitrile as mobile phase and detected at 265 nm, by conventional methodology validation. For fingerprint analysis, the RSDs of relative retention time and relative peak area of the characteristic peaks were within 0.07–0.78 and 0.94–9.09%, respectively. For simultaneous determination of vasicine, harmaline, harmine, deacetylpeganetin and peganetin, all calibration curves showed good linearity (r > 0.9990) within the test range. The relative standard deviations of precision, repeatability and stability test did not exceed 2.37, 2.68 and 2.67%, respectively. The average recoveries for the five analytes were between 96.47 and 101.20%. HPLC fingerprints play a minor role in authenticating and differentiating the herbs of different species of genus Peganum. However, the secondary metabolites levels of alkaloids and flavonoids in aerial parts of genus Peganum rely on species‐, habitat‐, and growth season‐dependent accumulation. Copyright © 2014 John Wiley & Sons, Ltd.     

A Photoinduced Cyclization Cascade—Total Synthesis of (−)‐Leuconoxine

A protecting‐group‐free and enantioselective total synthesis of the monoterpenoid indole alkaloid (?)‐leuconoxine was accomplished. The key step comprises a novel photoinduced domino macrocyclization/transannular cyclization involving the Witkop cyclization, for which additional mechanistic evidence is provided. This process furnishes a diaza[5.5.6.6]fenestrane skeleton, which is a hitherto unprecedented structure element.     

Development and validation of a rapid HPLC method for quantitation of SP‐141, a novel pyrido[b]indole anticancer agent,and an initial pharmacokinetic study in mice

There is an increasing interest in targeting the MDM2 oncogene for cancer therapy. SP‐141, a novel designed small molecule MDM2 inhibitor, exerts excellent in vitro and in vivo anticancer activity. To facilitate the preclinical development of this candidate anticancer agent, we have developed an HPLC method for the quantitative analysis of SP‐141. The method was validated to be precise, accurate, and specific, with a linear range of 16.2–32,400 ng/mL in plasma, 16.2–6480 ng/mL in homogenates of brain, heart, liver, kidneys, lungs, muscle and tumor, and 32.4–6480 ng/mL in spleen homogenates. The lower limit of quantification was 16.2 ng/mL in plasma and all the tissue homogenates, except for spleen homogenates, where it was 32.4 ng/mL. The intra‐ and inter‐assay precisions (coefficient of variation) were between 0.86 and 13.39%, and accuracies (relative errors) ranged from ?8.50 to 13.92%. The relative recoveries were 85.6–113.38%. SP‐141 was stable in mouse plasma, modestly plasma bound and metabolized by S9 microsomal enzymes. We performed an initial pharmacokinetic study in tumor‐bearing nude mice, demonstrating that SP‐141 has a short half‐life in plasma and wide tissue distribution. In summary, this HPLC method can be used in future preclinical and clinical investigations of SP‐141. Copyright © 2014 John Wiley & Sons, Ltd.     

Conformational studies on indole alkaloids from Flustra foliacea by NMR and molecular modeling

¹H and ¹³C NMR assignments for 1a–4a and 1b–4b were obtained using HSQC, HMBC and NOESY techniques. Differences and ambiguities from literature assignments are reconciled. For the pyrrolidine C‐ring, the combined use of NMR spectroscopy and molecular mechanics calculations revealed that this ring exists in a dynamic conformational equilibrium between twist (²T₁) and envelope‐twist (¹E–¹T₂) conformations. In chloroform‐d₁, the ¹H NMR coupling constants indicate that the pyrrolidine ring is biased in favor of the envelope‐twist conformation. Steric requirements of the N‐prenyl group enhanced the envelope‐twist (¹E–¹T₂) conformation populations. Copyright © 2002 John Wiley & Sons, Ltd.     

Preparatively useful transformations of steroids and morphine alkaloids by Mucor piriformis

A versatile fungus isolated in our laboratory and identified asMucor piriformis has been shown to effect novel and preparatively useful transformations in steroids and morphine alkaloids. The organism very effectively carries out hydroxylation of various C₁₉ and C₂₁ steroids at 7 and 14-positions. Although the organism is capable of catalysing hydroxylation at 6β and 1lα-positions, these are not the major activities. The 14α-hydroxylase appears to have a broad substrate specificity. However, steroids with a bulky substitution at C-17 α-position or without the 4-en-3-one group are not accepted as substrates by the 14α-hydroxylase system. Studies have demonstrated how various C₁₉ and C₂₁ steroids can be modified to yield new structures which are either difficult to prepare by traditional methods or hitherto unknown. The organism also very efficiently and selectively carries out the N-dealkylation of thebaine and its N-variants. Interestingly, the nor-compound formed does not get further metabolized. Since thebaine is very often used as a starting material to synthesize various morphine agonists as well as antagonists, and one of the steps involved in their preparation is the N-dealkylation reaction, the microbial process could certainly offer an alternative approach.     

Polarized Fluorescence of Jet‐Cooled Indole

The polarization of indole fluorescence on excitation in the P, Q, and R branches of a purely electron transition has been investigated. Relations are given to calculate the fluorescence polarization with arbitrary orientation of the dipole moments of transitions with absorption and emission and with excitation in the Q branch of the vibronic line. The coincidence of the measured (7.3%) and calculated (7.7%) values of the polarization degree confirms the reported intramolecular orientation of the dipole moment of transition. The measured fluorescence polarization degree on nonselective excitation is about 3%.     

Synthesis of isocryptolepine,an alkaloid fromCryptolepis sanguinolenta

Isocryptolepine, an alkaloid recently isolated from the roots ofCryptolepis sanguinotenta, was synthesized by selective methylation at the N(5) atom of 11H-indolo(3,2-c]quinoline with excess Mel in toluene.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp.2795–2796, November,1996