RESUMEN
Computer-assisted structure elucidation (CASE) using a combination of 1D and 2D NMR data has been available for a number of years. These algorithms can be considered as "logic machines" capable of deriving all plausible structures from a set of structural constraints or "axioms", defined by the spectroscopic data and associated chemical information or prior knowledge. CASE programs allow the spectroscopist not only to determine structures from spectroscopic data but also to study the dependence of the proposed structure on changes to the set of axioms. In this article, we describe the application of the ACD/Structure Elucidator expert system to help resolve the conflict between two different hypothetical hexacyclinol structures derived by different researchers from the NMR spectra of this complex natural product. It has been shown that the combination of algorithms for both structure elucidation and structure validation delivered by the expert system enables the identification of the most probable structure as well as the associated chemical shift assignments.
Asunto(s)
Algoritmos , Compuestos Epoxi/química , Sistemas Especialistas , Resonancia Magnética Nuclear Biomolecular , Compuestos Policíclicos/química , Modelos Moleculares , Estructura MolecularRESUMEN
Two new spirobicyclophosphonate isomers (19 and 20), conformationally constrained analogues of the potent competitive NMDA antagonist CGS 19755 (4), have been designed and synthetized with the aim of gaining insight into the conformational preference of the crucial distal phosphonate moiety at the antagonist NMDA binding site. The preliminary biological evaluation reveals that the activity as NMDA antagonist resides only in the (1R,5S,7R)-isomer (19), characterized by a (-)-gauche disposition around the C1-C5 bond, thus confirming previously reported pharmacophore models.
Asunto(s)
Antagonistas de Aminoácidos Excitadores/química , Ácidos Pipecólicos/química , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Sitios de Unión , Antagonistas de Aminoácidos Excitadores/síntesis química , Antagonistas de Aminoácidos Excitadores/farmacología , Ácido Glutámico/metabolismo , Modelos Moleculares , Conformación Molecular , Ácidos Pipecólicos/síntesis química , Ácidos Pipecólicos/farmacologíaRESUMEN
A submission to the Drug Enforcement Administration North Central Laboratory of a substance believed to be a structural analog of methaqualone hydrochloride precipitated an interest in being able to obtain a rapid and positive identification of such compounds. Both mass spectrometry and proton NMR spectroscopy (1-dimensional) provided evidence to suggest that the structural analog possessed a second methyl group in the molecule, relative to methaqualone, and that the methyl group was attached to the existing methyl-substituted phenyl ring. By application of proton 2-dimensional (2-D) NMR techniques, specifically the homonuclear shift correlation spectroscopy (COSY) and 2-D NOE (NOESY), the precise location of the methyl group in this unknown methaqualone analog was established and shown to have the structure 2.
Asunto(s)
Espectroscopía de Resonancia Magnética/métodos , Metacualona/análogos & derivados , Metacualona/química , Estructura MolecularRESUMEN
An ethanol extract of Aristolochia indica roots decreased fertility in both rats and hamsters when administered postcoitally (days 1-10 and 1-6, respectively). Petroleum ether (A), CHCl3 (B), and aqueous (C) fractions, tested similarly in rats, were inactive and/or toxic. Partition of fraction B afforded non-acidic (D) and acidic (E) fractions. Savinin (1), isolated from fraction D and not previously reported from the Aristolochiaceae , was inactive when administered postcoitally to rats. Aristolochic acid-I (2), reported previously from A. indica and isolated from fraction E, was inactive when administered postcoitally to rats and toxic when administered postcoitally to hamsters. (12S)-7,12- Secoishwaran -12-ol (3), previously reported from A. indica and isolated from fraction A, did not interrupt pregnancy when administered to mice on day 6 of pregnancy. Four additional compounds, aristolic acid (4) [prepared from aristolochic acid-I (2)], methyl aristolate (5) [prepared by methylating aristolic acid (4)], and cis- and trans-p-coumaric acid (both oblate commercially), were similarly tested in mice and found to be inactive. Aristolic acid (4), and the cis- and trans-p-coumaric acids also were inactive when administered postcoitally (days 1-10) to rats. Seven compounds reported previously from A. indica were also isolated, as were a new naphthoquinone, aristolindiquinone (6) (fraction E), and magnoflorine (fraction C).
Asunto(s)
Anticonceptivos Poscoito/aislamiento & purificación , Fertilidad/efectos de los fármacos , Extractos Vegetales/farmacología , Plantas Medicinales/análisis , Animales , Fenómenos Químicos , Química , Cricetinae , Estro/efectos de los fármacos , Femenino , Mesocricetus , Extractos Vegetales/análisis , Embarazo , Ratas , Ratas Endogámicas , Especificidad de la EspecieRESUMEN
Cleomiscosin A (1) has been isolated from Simaba multiflora and Soulamea soulameoides in the Simaroubaceae through bioactivity-directed fractionation and from Matayba arborescens in the Sapindaceae . The structure of cleomiscosin A (1) was established through spectroscopic studies and chemical reactions.