Chemical Interconversion Research Articles

New mycalolides from the marine sponge Mycale magellanica and their interconversion.

Three new macrolides, 30-hydroxymycalolide A (4), 32-hydroxymycalolide A (5), and 38-hydroxymycalolide B (6), were isolated from the marine sponge Mycale magellanica. Their structures were assigned on the basis of spectroscopic data. They were cytotoxic against L1210 cells with IC50 values of 0.019, 0.013, and 0.015 microg/mL, respectively. Chemical interconversion of the known mycalolides A-C (1-3) with 4-6 established their stereochemical relationships.

Quantum mechanics and the theory of hydrogen bond and proton transfer. Beyond a Born–Oppenheimer description of chemical interconversions

A recent quantum-mechanical theory of elementary chemical interconversion steps is extended and applied to discuss the fundamentals of hydrogen bonding and proton transfer. A chemical reaction, being a reshuffling of charges, is always coupled to an electromagnetic field, and corresponds to a change in quantum populations of a global Hamiltonian. The evolution goes via subsets of electronic quantum states defining bottleneck regions which, in turn, characterize the mechanisms. The elementary interconversion step is identified with quantum-dynamical processes where linear superpositions of relevant electronic quantum states couple the precursor (activated reactant) via bottleneck states to those defining successor (activated products) complexes. The coupling between different electronic states is made via the interaction with the electromagnetic field. Pictorially speaking, all interconverting species share the stationary nuclear geometry around which the bottleneck spectrum is built. This approach led to a non-BO mechanism for chemical interconversions. For steps mediated by ground-state-less molecular Hamiltonians (modelled, for instance, by saddle points at a Born–Oppenheimer (BO) level of computation) the reactants (products) must be moulded into the geometry of the bottleneck for the interconversion to take place as a Franck–Condon-like process. At the lowest level, the theory predicts the physical existence of collision (diffusion) pairs different from the hydrogen-bonded complexes. Discussions of experimental data show that the present theory gives a rationale to most of the phenomenological approaches developed to describe the properties of water (liquid and solid) and the prototropic mechanism in water.

Pinnatins A−E: Marine Diterpenes of the Rare Gersolane Class Derived from a Photochemically Induced Rearrangement of a Conjugated 2,5-Bridged Furanocembrane Precursor

A group of five highly functionalized polycyclic α,γ-disubstituted-α,β-unsaturated-γ-lactones (3−7) featuring a unique bicyclo [11.1.0] carbon skeleton joined in a trans fashion have been isolated from a Caribbean gorgonian, Pseudopterogorgia bipinnata. These rare marine diterpenoids can be regarded as representatives of the uncommon gersolane ring system. Two of the new metabolites, pinnatin A (3) and pinnatin B (4), showed significant differential antitumor activity in the National Cancer Institute's 60-cell-line tumor panel. The biogenesis of the pivotal metabolite pinnatin A (3) appears to involve a photochemically allowed [σ2a + π2a] cycloaddition process of a conjugated 2,5-bridged furanocembrane precursor. Structural assignments were accomplished through extensive spectroscopic analysis including 2D NMR, accurate mass measurements (HREIMS), X-ray crystallography, and chemical interconversions.

The unusual presence of hydroxylated furanosesquiterpenes in the deep ocean tunicate Ritterella rete. Chemical interconversions and absolute stereochemistry

Six new dendrolasin-type hydroxylated sesquiterpenes have been isolated from the cytotoxic extracts of the marine tunicate Ritterella rete. The absolute stereochemistry of the new compounds was determined by a combination of spectroscopic and chemical correlations, including derivatization with a recently introduced NMR reagent. This is the first time furanoterpenes have been isolated from a marine tunicate.

Systematic Search for New Types of Chemical Interconversions: Mathematical Models and Some Applications

According to Formal−Logical Approach to Organic Reactions, the systematical search for new, unprecedented types of chemical interconversions needs the complete sets of symbolic, reaction, structural, and skeletal equations to be generated. In this paper, the generation problems are shown to be reduced to graph labeling problems and, more precisely, to constructive enumeration problems for orbit representatives of induced permutation groups acting on certain sets of vertex or edge labelings of well-defined graphs. The suggested combinatorial models make it possible to take into account formal charges and unshared electrons (needed to describe ionic, radical, and oxidation−reduction processes) and unchanged bonds forming cycles (included in cyclic structures of educts and products and needed to describe, e.g., degenerate rearrangements). The basic ideas of the effective generating algorithms, some results of the corresponding analytical enumeration techniques, and several new reaction types found by compute...

Identification and Characterization of Pectenotoxin (PTX) 4 and PTX7 as Spiroketal Stereoisomers of Two Previously Reported Pectenotoxins.

Pectenotoxins (PTXs) isolated from the scallop Patinopecten yessoensis were shown to be involved in an episode of diarrhetic shellfish poisoning (DSP). A total of eight analogues (PTX1-PTX7 and PTX10) have been isolated to date, and the structures of four of these analogues (PTX1, PTX2, PTX3, and PTX6) have already been elucidated. Here, we report the characterization of PTX4 and PTX7 as 7-epi-PTX1 and 7-epi-PTX6, respectively, on the basis of NMR data and an acid-catalyzed chemical interconversion. The structures of two new artifacts, PTX8 and PTX9, produced following this treatment are also reported.

Antileishmanial cyclic peroxides from the Palauan sponge Plakortis aff. angulospiculatus

As part of a program to discover new drugs for the treatment of tropical diseases, we have isolated and identified six new metabolites from the Palauan sponge Plakortis aff. angulospiculatus. Two cyclic peroxides show strong in vitro antiproliferative effects on promastigotes of Leishmania mexicana, a flagellate protozoan that causes leishmaniasis. The structures of the cyclic peroxides 1, 2 and 5 and furans 3, 4 and 6 were elucidated by interpretation of spectroscopic data, molecular modelling, and chemical interconversions.

New Types of Potentially Antimalarial Agents: Epidioxy‐substituted norditerpene and norsesterpenes from the marine sponge Diacarnus levii

AbstractNatural free carboxylic acids from the hadromerid sponge Diacarnus levii (Kelly‐Borges and Vacelet) were esterified to yield the new cyclic norditerpene peroxides ent‐muqubilin benzyl ester (= (αR,3S,6R)‐α,6‐dimethyl‐6‐[(E)‐4‐methyl‐6‐(2,6,6‐trimethyl‐cyclohex‐1‐en‐1‐yl)hex‐3‐enyl]‐1,2‐dioxan‐3‐acetic acid benzyl ester; 6, diacarnoate B methyl ester(= (αS,3R,6R)‐α,6‐dimethyl‐6‐{2‐(4aS,8aS)‐3,4,4a,5,6,7,8,8a‐octahydro‐3‐oxo‐2,5,5,8a‐tetramethylnaphthalen‐1‐yl)ethyl}‐1,2‐dioxan‐3‐acetic acid methyl ester; 9), and deoxydiacarnoate B benzyl ester (= (αS,3R,6R)‐α,6‐dimethyl‐6‐{2‐[(4aS,8aS)‐3,4,4a,5,6,7,8,8a‐octahydro‐2,5,5,8a‐tetramethyl‐1‐naphthalenyl]ethyl}‐1,2‐dioxan‐3‐acetic acid benzyl ester; 10), which were isolated following extensive chromatography. The relative configuration of the peroxide/α‐methylacetate moiety of 6, 9, and 10, was directly determined from their NMR spectra. The absolute configurations of the peroxide/α‐methylacetate moiety was deduced from comparative 1H‐NMR data of the (S)‐ and (R)‐phenylglycine methyl ester derivatives 7 and 8 as well as 11/13 and 12/14, all obtained from a mixture of the precursors of 3, 6, and 10. The absolute configuration at the carbobicyclic moiety of enone 9 and of 10, is identical, as established by chemical interconversion, 9 and 10 belong to the normal labdane series according to empirical CD rules, applied either directly to 9 or to the parent (+)‐sclareolide‐derived enone 20. In contrast, molar rotation additivity rules suggest the ent‐labdane configuration for 9 and 10. The epidioxides 1–3, 6, and 10 proved active in vitro against the malaria parasite Plasmodium falciparum; especially the previously isolated methyl 3‐epinuapapuanoate (2) was active against a chloroquine‐resistant strain, and this with a good security index.

18] Transport and drug binding kinetics in membrane vesicle preparation

This chapter describes the transport and drug binding kinetics in membrane vesicle preparation. It discusses the isolation of plasma membrane vesicles from PC-12 rat pheochromocytoma cells, which express the norepinephrine (NE) transporter. The chapter also highlights how plasma membrane vesicles can be used to study kinetics of substrate transport and drug binding to the transporter. Neurotransmitter transporters are the primary targets of a series of psychoactive compounds. Neurotransmitter transporters are also targets for useful therapeutic drugs. Substances, such as tiagabine, which bind to the γ-aminobutyric acid (GABA) transporter and inhibit GABA reuptake are used as antiepileptic drugs. Binding studies using membrane vesicles isolated from tissues or cells expressing one of these transporters have contributed to understanding of their interaction with transporters. Plasma membrane vesicles isolated from a tissue or from a clonal cell population expressing large amounts of a specific transporter have provided important insights into the driving forces and chemical interconversion associated with transport of molecules across cell membranes.

New Furanoterpenoids from the Sponge Spongia officinalis

The sponge Spongia officinalis from La Caleta, Cadiz, Spain, contains the new C-21 furanoterpenes furospongin-5 (1) and cyclofurospongin-2 (2) and the new furanosesterterpene demethylfurospongin-4 (3), in addition to the known terpenoids 4-11. The structures of compounds 1-3 were elucidated by interpretation of spectral data and chemical interconversions. Furospongin-5 (1) was weakly cytotoxic against the P-388 cell line (ED 50 = 5 μg/mL).

New diterpenoids from the alga Dictyota dichotoma

The marine alga Dictyota dichotoma from Cortadura (Cádiz, Spain) contains, in addition to nineteen known diterpenes (8–26), the new dolabellanes, (1R,2E,4S,5R,6S,7E,10S,11S,12R)-5,6,18-triacetoxy-10-hydroxy-2,7-dolabelladiene (1), (1R,2E,4R,7E,10S,11S,12R)-18-acetoxy-10-hydroxy-2,7-dolabelladiene (2), (1R,2E,4S,5R,7E,10S,11S,12R)-5-acetoxy-10,18-dihydroxy-2,7-dolabelladiene (3), (1R∗,3E,7S∗,8S∗,11S∗,12R∗)-7,8-epoxy-3,18-dolabelladiene (4), and (1R∗,2E,4R∗,7E,11S∗,12R∗)-18-acetoxy-2,7-dolabelladiene (5) together with two new hydroazulene diterpenes, isopachydictyol A (6) and dictyotatriol A (7). The structures of the new compounds were elucidated by interpretation of spectroscopic data and the absolute configurations of compounds 3, 7 and 10 were established using the Mosher's method and of compounds 1, 2, and 11 by chemical interconversions. The new diterpenes isolated from D. dichotoma showed mild cytotoxicity against four tumor cell lines excepting compounds 1 and 7 that were inactive. Dolabellane 2 exhibited the greatest activity.

A quantum electronic theory of chemical processes?The inverted energy profile case: CH3+ + H2 reaction

A quantum approach to chemical processes is developed. The chemical interconversion is described as an electronic process. The reaction corresponds to histories involving quantum states belonging to different stationary molecular Hamiltonians. The system may be embedded in a weak (thermal) and/or external electromagnetic field. The electromagnetic transverse fields lead to transition moments yielding finite probability amplitudes for the system to change from one quantum state to another. Bottleneck subspaces (transition states) are defined; they mediate the interconversions in generic unimolecular and bimolecular processes. Active precursor and successor complexes are introduced to help bridge reactant and product electronic states. The stationary states are modeled with Born-Oppenheimer Hamiltonians. At a qualitative level, the theory is general. The rate, measured as a time derivative of product concentration, is expressed in terms of concentrations of active precursor and successor complexes. The kinetic coefficients are given in terms of quantum processes involving electronic bottleneck states. Stationary structures and vibrational zero-point energies characterizing the reactive CH3++H2 system are determined at a Hartree-Fock level of theory with 6-31++G** basis set. The vibrational levels are corrected with anharmonicity effects. The saddle point of index one for hydrogen scrambling reactions has been obtained and shown to be related to the CH5+ molecular complex together with the precursor and successor complexes geometries. The unusual properties of the system with respect to standard transition-state theory are fairly well described within this approach, in particular, isotope scrambling as well as photon emission during formation of the carbocation. The theory suggests that these types of reactions, which are found in outer space, may contribute to the scattering of the cosmic microwave background. © 1997 John Wiley & Sons, Inc.

A quantum electronic theory of chemical processes—The inverted energy profile case: CH3 + H2 reaction

A quantum approach to chemical processes is developed. The chemical interconversion is described as an electronic process. The reaction corresponds to histories involving quantum states belonging to different stationary molecular Hamiltonians. The system may be embedded in a weak (thermal) and/or external electromagnetic field. The electromagnetic transverse fields lead to transition moments yielding finite probability amplitudes for the system to change from one quantum state to another. Bottleneck subspaces (transition states) are defined; they mediate the interconversions in generic unimolecular and bimolecular processes. Active precursor and successor complexes are introduced to help bridge reactant and product electronic states. The stationary states are modeled with Born-Oppenheimer Hamiltonians. At a qualitative level, the theory is general. The rate, measured as a time derivative of product concentration, is expressed in terms of concentrations of active precursor and successor complexes. The kinetic coefficients are given in terms of quantum processes involving electronic bottleneck states. Stationary structures and vibrational zero-point energies characterizing the reactive CH3++H2 system are determined at a Hartree-Fock level of theory with 6-31++G** basis set. The vibrational levels are corrected with anharmonicity effects. The saddle point of index one for hydrogen scrambling reactions has been obtained and shown to be related to the CH5+ molecular complex together with the precursor and successor complexes geometries. The unusual properties of the system with respect to standard transition-state theory are fairly well described within this approach, in particular, isotope scrambling as well as photon emission during formation of the carbocation. The theory suggests that these types of reactions, which are found in outer space, may contribute to the scattering of the cosmic microwave background. © 1997 John Wiley & Sons, Inc.

Transition structures for hydride transfer reactions in vacuo and their role in enzyme catalysis

A general discussion as to the role of in vacuo transition structure in enzyme catalysis is presented. Quantum mechanical aspects are emphasized. The transition structures defined as saddle points of index one (SPi-1) for the hydride transfer step on different model enzyme systems from flavoproteins to dehydrogenases have been characterized with analytical gradients at different levels of theory: semi-empirical; ab initio with different basis sets within the Hartree-Fock scheme; density functional theory using different approaches. Quantum chemical characteristics of the SPi-1 are used to discuss hydride transfer step in enzyme catalyzed reactions and mechanistic implications. With the exception of dihydrofolate reductase, the results for all other systems studied suggest that the endo relative orientation imposed by the active site on the reactants is essential for polarizing the C dH t bond and situating the system in the quadratic region of the endo SPi-1. The geometry and transition vector components are both model independent and weakly dependent on the level of theory used in their determination. Comparisons of the SPi-1 geometries with available X-ray coordinates show that the SPi-1 can be fitted without any stress at the active site. The geometrical arrangement of the SPi-1 results in optimal frontier LUMO orbital interactions, and the transition vector amplitudes show primary and secondary isotope effects to be strongly coupled. A comparison between simple and sophisticated molecular models shows that there is a minimal molecular model associated with geometrical parameters describing the essentials of the chemical interconversion step. For hydride transfer, the corresponding transition vector is an invariant feature.

Theoretical characterization of transition structure for the enzyme-catalyzed reaction at the active center of lactate dehydrogenase. Geometry and transition vector dependence upon computing method and model system

A theoretical study of the catalytic mechanism of lactate dehydrogenase enzyme on different model systems was carried out with the help of the PM3 semi-empirical procedure and an ab initio method at the 4-31G and 6-31G** basis sets at a Hartree-Fock (HF) level of theory. The geometry, transition vector (TV) and electronic structure of the transition structure (TS) for the acid-catalysed hydride reduction were obtained. The dependence of these properties on the computing method and model system is analysed and discussed. Proton transfer is much more advanced than hydride transfer occurring in roughly perpendicular planes. All the TSs render very similar structural features, the control of the chemical reaction being associated with the hydride transfer process. A comparison among simple and sophisticated molecular models shows that the TS seems to be structurally a rather robust entity. There is a minimal molecular model with a TS which describes the essentials of the chemical interconversion step in a given enzyme mechanism and the corresponding TV is an invariant feature.

An imidazole alkaloid and other constituents from Pilocarpus trachyllophus

Roots of Pilocarpus trachyllophus yielded (−)-episesamin, hesperidin, tridecan-2-one, 1-hydroxytridecan-2-one, N-isobutyl-deca-2(E),4(E)-dienamide, pilocarpine and a new imidazole alkaloid, 13-nor-7(11)-dehydropilocarpine. Except for pilocarpine and tridecan-2-one, this is the first report of these substances in the genus Pilocarpus. Structural determinations were accomplished by spectroscopic analysis, particularly two-dimensional NMR, chemical interconversion and, where appropriate, comparison with literature data.

Transition structure for hydride transfer from cyclopropene to azirinium cation

The transition structure for the hydride transfer between the cyclopropene and azirinium cation has been characterized by means of the ab initio method at the 3-21G, 4-31G, 6-31G, 6-31 + + G ∗ basis set levels. There are two transition structures for the exo and endo conformations. The transferring hydrogen is located closer to the acceptor centre, nitrogen atom, than to the donor centre, carbon atom, with an almost bent arrangement. The electronic structure and transition vector are basis set level independent. For the transition structures, the endo is more stable than the exo conformation due to a favourable orbital interaction. An analysis of calculated transition structure associated with the hydride transfer step in different model systems shows that the use of very simple models to represent this step do not alter their nature. The transition structures for hydride transfer step seems to be a robust entity. Furthermore, there is a minimal molecular model with a transition structure and transition vector which describes the essentials of the chemical interconversion step.

Deoxyspongiaquinones: New Sesquiterpene Quinones and Hydroquinones From a Southern Australian Marine Sponge Euryspongia sp.

Chemical investigation of a marine sponge, Euryspongia sp., collected from the Great Australian Bight, Australia, resulted in the isolation of two new sesquiterpene quinones , deoxyspongiaquinone (4) and (E)-chlorodeoxyspongiaquinone (5), as well as two sesquiterpene hydroquinones, deoxyspongiaquinol (6) and (E)-chlorodeoxyspongiaquinol (7). The structures for (4)-(7) were determined by detailed spectroscopic analysis, as well as chemical interconversion and degradation.

Biologically active flavonoids and terpenoids from Egletes viscosa

The steam volatile components from the hexane extract of dried flower buds of Egletes viscosa were identified by gas chromatography-mass spectrometry as trans-carvyl acetate, cis-carvyl acetate, sabinyl acetate, verbenyl acetate, cyclopentaethylidene, geranyl acetate and 5-methylfuranone, and trans-pinocarvyl acetate (major component). From the non-volatile residue, centipedic acid and a novel clerodane diterpene, 12-acetoxy-hawtriwaic acid lactone, were isolated. From the ethanol extract, ternatin (4′,5-dihidroxy-3,3′,7,8-tetramethoxyflavone), was isolated. Ternatin showed anti-inflammatory, hepatoprotection and gastroprotection properties, and, according to the NCI protocols, it showed moderate activity against HIV. The diterpenes showed antispasmodic activity. Structure determination of these secondary metabolites was accomplished by spectrometric methods, including 2D NMR, chemical interconversion and X-ray crystallographic analysis.

Alkaloids ofArundo donax. III. Reconsideration of the structures of donaxarine and donaxaridine

The alkaloid composition of the epigeal part of Arundo donax has been studied, and from an ether extract have been isolated the alkaloids donaxine, arundine, deoxyvasicinone, N-phenyl-β-naphthylamine, donaxarine, and donaxaridine. On the basis of an x-ray structural analysis, new structures have been established for donaxarine and donaxaridine:spiro[(N-methylpyrrolidin-2-one)-3,4′-(2′-methyl-3′,1′-benzoxazine)] and 3-hydroxy-3-(2′-aminophenyl)-N-methyl-2 pyrrolidone, respectively. Spectral characteristics of the derivatives obtained are given and their chemical interconversions are described.