María A. Bucio

Stereostructure reassignment and absolute configuration of isoepitaondiol, a meroditerpenoid from Stypopodium flabelliforme.

Careful examination of the published NMR data for isoepitaondiol, a meroditerpenoid from Stypopodium flabelliforme, suggests that its published structure 1 must be revised. On the basis of extensive 1D and 2D NMR studies, we now propose that structure 2, with a trans-anti-trans-anti-cis arrangement fits isoepitaondiol diacetate. The relative configuration of 2 was confirmed by single-crystal X-ray diffraction, while the absolute configuration was evidenced by vibrational circular dichroism in combination with DFT B3LYP/DGDZVP calculations.

Bioactive Montanine Derivatives from Halide-induced Rearrangements of Haemanthamine-type Alkaloids. Absolute Configuration by VCD

An unexpected rearrangement of haemanthamine-type alkaloids in the presence of halogenating agents has been found. Rearranged compounds present the 5,11-methanomorphantridine framework characteristic of montanine-type alkaloids. These compounds are difficult to obtain because of their scarcity in natural sources and because the synthetic approaches developed so far require numerous steps. Vibrational circular dichroism (VCD) spectroscopy was used to determine the absolute configuration of one of the rearranged compounds. Several rearranged alkaloids showed antimalarial activity.

Absolute configuration of tropane alkaloids from Schizanthus species by vibrational circular dichroism

The absolute configuration (AC) of 6beta-hydroxy-3alpha-senecioyloxytropane (1), 3alpha-hydroxy-6beta-tigloyloxytropane (2), 3alpha-hydroxy-6beta-senecioyloxytropane (3), and 3alpha-hydroxy-6beta-angeloyloxytropane (4) was assigned as (1R,3R,5S,6R) using density functional theory (DFT) calculations at the B3LYP/DGDZVP level of theory in combination with experimental vibrational circular dichroism (VCD) measurements and comparison with the spectra of similar tropanes. The AC of 1 followed from a sample isolated from Schizanthus grahamii, while those of the mixture of 2 and 3, isolated from the same source, were determined by comparing the VCD measurement to a weighted calculation of the individual VCD spectra according to a 69:31 ratio of 2:3 determined by (1)H NMR signal integration. In turn, Schizanthus pinnatus provided a 7:3 mixture of 1:4 whose AC was determined using the experimental VCD absorptions in the 1150-950 cm(-1) spectral region which were compared with those observed for 1-3 and with those described for other 3alpha,6beta-tropanediol derivatives.

Chiral recognition of diastereomeric 6-cedrols by vibrational circular dichroism

The use of vibrational circular dichroism spectroscopy for the chiral recognition of the two epimers of 6-cedrol, tricyclic sesquiterpenes, which contains oxygen as the heaviest atom, is shown. Bands in the 1500-850 cm(-1) region of the spectra were analyzed to calculate the anisotropy factors (g), which provided the regions of maximum circular dichroism effect for each epimer.

Determination of absolute configuration of salvic acid, an ent-labdane from Eupatorium salvia, by vibrational circular dichroism

The relative stereochemistry at C13 and the absolute configuration of salvic acid, a constituent of the leaves of Eupatorium salvia, were established as the 13-(R)-ent-labdane 1. The results follow from vibrational circular dichroism measurements of the derived O-methyl ether methyl ester 3 which were compared to DFT B3LYP/DGDZVP calculated spectra. The relative stereochemistry of salvic acid at C13 was independently verified by single crystal X-ray diffraction measurements of 1, and of its derived diol 4.

FORMAL SYNTHESIS OF ()-PHYSOSTIGMINE

Abstract The formal synthesis of the indole alkaloid (±)-physostigmine (1) from (Z)-2-hydroxy-5-methoxyindolenine9 is described. The key step of the synthesis is a novel diasteroselective conjugated addition of a Grignard reagent to 9. The relative stereochemistry of the newly formed contiguous chiral centers is established by X-ray crystallography. The stereocontrolled conjugated addition involves the directing effect of the neighboring hydroxyl group to afford 12. Oxidation of 12 with CrO 3 AcOH leads to oxindole 14. Decarboxylation of the latter, followed by N-methylation gave 2,3-dihydro-5-methoxy-1,3-dimethyl-2-oxo-1H-indole-3-acetonitrile (3), a known precursor for physostigmine (1).

Nouvelle voie d'accès au squelette de la (±)-physostigmine

Abstract Grignard 1,4-addition of methyl magnesium iodide to 2-hydroxyindolenine 3, followed by oxydation with CrO3/AcOH, led diastereoselectively to methyl 2-cyano-2-(1-carbomethoxy-3-methyl-2-oxo-3-indolyl)acetate 5. Decarboxylation of 5 and thence N-methylation gave 3-acetonitril-3-methylindol-2-one, 2, which is an intermediate in the synthesis of the (±)-physostigmine 1 framework.

Vibrational circular dichroism discrimination of diastereomeric cedranol acetates.

The reliability of vibrational circular dichroism (VCD) spectroscopy to discriminate four diastereomeric cedranol acetates 1-4 by means of their absolute configuration is examined. The usage of CompareVOA software to quantify comparisons of the measured infrared (IR) and VCD spectra with the corresponding simulated spectra at the B3LYP/DGDZVP and B3PW91/DGDZVP levels of theory for each diastereomer enabled the B3PW91 functional to be qualified as superior to the B3LYP functional for vibrational calculations of 1-4. Analogously, a set of quantitative VCD spectra cross-comparisons of 1-4 unambiguously distinguished the diastereomers using B3PW91 and failed using B3LYP. Remarkably, quantitative IR spectra cross-comparisons of 1-4 using B3PW91 or B3LYP functionals demonstrated that the achiral spectroscopic IR technique is not able to distinguish cedranol acetate diastereomers. VCD comparisons using anisotropy g-factor values of bands in the 1550-950 cm(-1) region of the spectra were of aid to facilitate visual spectra matching for each diastereomer.

In vitro anti-influenza screening of several Euphorbiaceae species: Structure of a bioactive Cyanoglucoside from Codiaeum variegatum

A bio-guided screening against influenza A virus (FLUAV) was carried out with seven Euphorbiaceae species. The results showed that chromatographic fractions from Phyllantus niruri, Euphorbia pulcherrima and Codiaeum variegatum had relevant anti-FLUAV activity, although only chromatographical subfractions from C. variegatum kept the activity. From this plant, the active compound against FLUAV was isolated. Its structure was assigned as 2-(3,4,5)-trihydroxy-6-hydroxymethyltetrahydropyran-2-yloxymethyl)acrylonitrile (1) on the basis of NMR, mass spectrometry and X-ray diffraction analysis. The compound displayed virucidal activity without impairment of haemagglutination properties of the used virus strain. This is the first report indicating antiviral activity of a cyanoglucoside.

Vibrational Circular Dichroism (VCD), VCD Exciton Coupling, and X-ray Determination of the Absolute Configuration of an α,β-Unsaturated Germacranolide

The absolute configuration of was deduced by vibrational circular dichroism together with the evaluation of the Flack and Hooft X-ray parameters. Vibrational circular dichroism exciton coupling, using the carbonyl group signals, confirmed the absolute configuration of . In addition, sodium borohydride reduction of the 11,13-double bond of 6-epi-desacetyllaurenobiolide () yields an almost equimolecular mixture of C11 epimers, while reduction of the same double bond of 6-epi-laurenobiolide () provided almost exclusively the (11S) diastereoisomer .