Pedro Joseph-Nathan

Antifeedant and Phytotoxic Activity of the Sesquiterpene p -Benzoquinone Perezone and Some of its Derivatives

The sesquiterpene p-benzoquinone perezone (1), isolated from Perezia adnata var. alamani (Asteraceae), and its non-natural derivatives isoperezone (2), dihydroperezone (3), dihydroisoperezone (4), and anilidoperezone (5) were tested as antifeedants against the herbivorous insects Spodoptera littoralis, Leptinotarsa decemlineata, and Myzus persicae. Compounds 1–5 exhibited strong antifeedant activity against L. decemlineata and M. persicae, and elicited a low response by S. littoralis. Antifeedant activity on L. decemlineata and M. persicae increased when the hydroxyl group at C-3 in perezone (1) was changed to C-6 to give isoperezone (2). The same effect was found with hydrogenation of the double bond of the alkyl chain of (1) to yield dihydroperezone (3). In contrast, hydrogenation of this double bond in isoperezone (2) to give dihydroisoperezone (4) led to a reduction in antifeedant activity. Determination of the phytotoxic activity of 1–5 revealed that 3 had a significant inhibition effect on Lactuca sativa radicle length growth.

NMR and X-ray diffraction studies of two bicyclic borates containing chiral boron and nitrogen atoms

Abstract Ring closure between the nitrogen and boron atoms during the syntheses of bicyclic organoboron compounds occurs under asymmetric induction, since reactions of optically active N-methyl-N-(1-methyl-2-phenyl-2-hydroxyethyl)glycines with 4-bromophenylboronic acid or with 1,4-phenylenediboronic acid provides the corresponding bicyclic boron derivatives (N → B)-4-bromophenyl[N-methyl-N- (1-(S)-methyl-2-(R)-phenyl-2-oxyethyl)aminoacetate-O,O′,N]boron (3a–3b), (N → B)-4-bromophenyl[N-methyl-N-(1-(S)-methyl-2-(S)-phenyl-2-oxyethyl)aminoacetate-O,O′,N]boron (4a–4b), (N → B)(N′ → B′)-1,4-phenylenebis[N-methyl- N-(1-(S)-methyl-2-(R)-phenyl-2-oxyethyl)aminoacetate-O,O′,N]bis-boron (5) and (N → B)(N′ → B′)-1,4-phenylenebis[N-methyl-N-(1-(S)-methyl-2-(S)-phenyl-2-oxyethyl)aminoacetate-O,O′,N]bisboron (6) in high stereochemical yields. The configuration of the nitrogen and boron atoms in 6 and in (N → B) phenyl[N-methyl-N-(1-(S)-phenyl-2-oxyethyl)aminoacetate-O,O′,N]boron (2) is established by single crystal X-ray diffraction studies.

Stereochemical Analysis of Leubethanol, an Anti-TB-Active Serrulatane, from Leucophyllum frutescens

Bioactivity-guided fractionation of the methanolic root bark extract of Leucophyllum frutescens led to the identification of leubethanol (1), a new serrulatane-type diterpene with activity against both multi-drug-resistant and drug-sensitive strains of virulent Mycobacterium tuberculosis. Leubethanol (1) was identified by 1D/2D NMR data, as a serrulatane closely related to erogorgiane (2), and exhibited anti-TB activity with minimum inhibitory concentrations in the range 6.25-12.50 μg/mL. Stereochemical evidence for 1 was gleaned from 1D and 2D NOE experiments, from 1H NMR full spin analysis, and by comparison of the experimental vibrational circular dichroism (VCD) spectrum to density functional theory calculated VCD spectra of two diastereomers.

A PC program for calculation of dihedral angles from 1H NMR data

Abstract The program ALTONA, written in BASIC, calculates plots of H-C-C-H dihedral angles from proton-proton NMR vicinal coupling constants using an empirically generalized Karplus-type equation, which takes into account the electronegativity and the orientation of the substituents attached to the considered H-C-C-H fragment. Generation of a plot for the fragment results after introduction of the atomic symbols of the substituents (C, H, O, N, S, P, F, Cl, Br, and/or I) and their orientation (+ or −). ALTONA is compiled in Turbo BASIC for PC compatible computers and is included in the present paper as ALTONA.EXE on disk.

A Novel Manich Type Reaction Using Aminals in Alkaline Medium

Abstract A one-step synthesis of 1,3-bis[2′ -hydroxy-5, - substituted-benzyl] imidazolidines (3a-d) using a mannich type reaction in basic media is described.

Synthesis and biological evaluation of (-)- and (+)-debromoflustramine B and its analogues as selective butyrylcholinesterase inhibitors.

A series of pyrrolidinoindolines have been synthesized as debromoflustramine B (4a) analogues for their evaluation as cholinesterase inhibitors. Structure-activity studies of this series revealed the optimum pharmacophoric elements required for activity and resulted in the discovery of selective butyrylcholinesterase inhibitors with micromolar potency. Biological testing demonstrated that (-)-4a was 7500 times more potent than its enantiomer (+)-4b. The most active inhibitor against BChE in the series was demethyldebromoflustramine B (5a), with an IC50 value of 0.26 microM. X-ray crystallography of 15 and docking studies of selected compounds into human BChE (PDB 1POI) are presented. Molecular modeling studies showed that pi-hydrogen bond, classical hydrogen bond, and cation-pi interactions are critical for optimum potency.

Syntheses and structures of two new dibenzobicyclic phenylboronates

Abstract The preparation, spectroscopic data and structure determination of ( N  B )-phenyl[amino-2,2′-diphenolate- O ,O′, N ]borane ( 3 ) and of ( N  B )-phenyl[ N -methyl-amino-2,2′-diphenolate- O , O ′ N ]borane ( 4 ) derived from 2,2′-diphenolamine ( 5 ) and from N -methyl-2,2′-diphenolamine ( 6 ), respectively, are described. The structure of 3 was further demonstrated by X-ray diffraction studies.

Absolute configuration of ()-myrtenal by vibrational circular dichroism

The VCD spectrum of the monoterpene (-)-myrtenal (1) was compared with theoretical spectra using ab initio density functional theory (DFT) calculations at the B3LYP/6-31G(d,p), B3LYP/6-31G+(d,p), B3LYP/6-311G+(d,p), B3LYP/DGDZVP, and B3PW91/DGTZVP levels of theory. Conformational analysis of 1 indicated that the lowest energy conformer was s-trans-C2-C10, which contributes more than 98.5% to the total conformational population regardless of the employed level of theory. The use of a recently developed confidence level algorithm demonstrated that VCD spectra calculated for the main conformer, using the indicated hybrid functionals and basis set, gave no significant changes, from where it follows that B3LYP/DGDZVP calculations provide a superior balance between computer cost and VCD spectral accuracy. The DGDZVP basis set demanded around a quarter the time than the 6-311G+(d,p) basis set while providing similar results. The spectral comparison also provided evidence that the levorotatory enantiomer of myrtenal has the 1R absolute configuration.

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.