Synthesis of (−)-auricularic acid and its C-4 epimer the absolute configuration of auricularic acid
Abstract A synthesis of (−)-auricularic acid (2a) starting from methyl (+)-13-oxo- podocarp-8(14)-en-19-oate (3a) and a synthesis of its C-4 epimer (2b) starting from methyl (+)-13-oxopodocarp-8(14)-en-18-oate (3b) are described. The absolute configuration of natural auricularic acid is stablished as (4R, 5S, 8S, 9R, 10S, 14S).
Chemoselective reactions of N1-methyl-2-hydroxy-3-methylamino-3-phenylpropanamide with electrophiles. Synthesis of chiral hexahydro-4-pyrimidinones and oxazolidines
Abstract The reactivity of (2S,3S)-N1-methyl-2-hydroxy-3-methylamino-3-phenylpropanamide 1 , containing three nucleophilic centres has been studied against dihaloalkanes and aldehydes. Hexahydro-4-pyrimidinones or oxazolidines were obtained chemoselectively. Experimental results were explained by ‘ab initio’ calculations.
Synthesis of (+)-podocarp-8(14)-en-13-one and methyl-(+)-13-oxo-podocarp-8(14)-en-18-oate from abietic acid
Abstract An efficient method for the preparation of (+)-podocarp-8(14)-en-13-one 6 and methyl-(+)-13-oxo-podocarp-8(14)-en-18-oate 8 from abietic acid is described.
Experimental and theoretical DFT study of the reaction of 3-amino-1,2-diols with dichloromethane and paraformaldehyde
Abstract The reactions of 3-phenyl-3-methylamino-1,2-propanediol 1a and 3-[(tert-butyldimethylsilyl)oxy]-1-methylamino-1-phenyl-2-propanol 1b with (CH2O)n and CH2Cl2 are appropriate procedures for the preparation of 1,3-oxazines or 1,3-oxazolidines under proper selection of kinetic or thermodynamic reaction conditions. The reaction of 1b with (CH2O)n or CH2Cl2, affords the oxazolidine 2b under kinetic conditions and then this compound can be slowly converted into 5-[(tert-butyldimethylsilyl)oxy]-3-methyl-4-phenyl-3,4,5,6-tetrahydro-2H-1,3-oxazine 3b under thermodynamic control. The mechanism proposed for this transformation and the effect of polar solvents on the acceleration of the reactio…
Enantioselective Synthesis of Cuparane Sesquiterpenes. Synthesis of (−)-Cuparene and (−)-δ-Cuparenol
(−)-Cuparene and (−)-δ-cuparenol, two cuparane-type sesquiterpenoids, were synthesized from β-cyclogeraniol in 47% and 27% overall yield, respectively, using a Katsuki−Sharpless asymmetric epoxidat...
Synthesis of spongian diterpenes: (−)-spongian-16-oxo-17-al and (−)-acetyldendrillol-1
Abstract An efficient diastereoselective synthesis of the spongian diterpenes (−)-spongian-16-oxo-17-al ( 1 ) and (−)-acetyldendrillol-1 ( 13 ) is described starting from (+)-podocarp-8(14)-13-one ( 6 ) via the ester-dialdehyde 11 as key intermediate. The absolute configuration at C-17 in synthetic compound 13 has conclusively been proved by NOE experiments.
Quantitative ring contraction of 5-hydroxy-1,3-oxazin-2-ones into 5-hydroxymethyl-1,3-oxazolidin-2-ones: A DFT study
Abstract The ring contraction of trans -5-hydroxy-1,3-oxazin-2-ones 1 into cis -5-hydroxymethyl-oxazolidinones 3 was studied with different bases and nucleophiles and it was found that it is the basicity and not the nucleophilicity the factor responsible for the ring contractions. A DFT study was made for the proposed mechanism.
Triazolopyridines. Part 28. The ring–chain isomerization strategy: triazolopyridine- and triazoloquinoline–pyridine based fluorescence ligands
Abstract The ring–chain isomerization of [1,2,3]triazolo[1,5-a]pyridines or [1,2,3]triazolo[1,5-a] quinolines has been efficiently employed as a tool to provide tridentate fluorescent structures. Based on these scaffolds, a new family of highly fluorescent compounds has been synthesized and evaluated for the recognition of zinc or copper cations. In addition, the 1:1 Zn+2-L complex of a naphthalene triazolopyridine–pyridine derivative revealed high efficiency as sensor for anions providing large binding constants for nitrite and cyanide.
A DFT study of the mechanism of NHC catalysed annulation reactions involving α,β-unsaturated acyl azoliums and β-naphthol.
The mechanism of NHC catalysed annulation reactions involving an α,β-unsaturated acyl azolium and β-naphthol has been studied using DFT methods at the MPWB1K/6-311G(d,p) level in toluene. For the C-C bond formation step, which corresponds to the rate- and stereo-determining step of this NHC catalysed reaction, the two competitive addition modes, i.e. the 1,2- and the 1,4-additions, have been studied. In toluene, acyl azolium forms an ion pair (IP) with the counterion chloride anion. Interestingly, β-naphthol forms a hydrogen bond with the chloride anion of IP, increasing the nucleophilic character of β-naphthol and the electrophilic character of the acyl azolium moiety. For the first time, …
Diastereoselective synthesis of spongian diterpenes. Total synthesis of the furanoditerpene (−)-spongia-13(16),14-diene
Abstract An effective diastereoselective synthesis of the marine-sponge metabolite (−)-spongia-13(16),14-diene 1 is achieved starting from S-(+)-carvone via a homochiral phenanthrenone as the key intermediate for the construction of the furan ring system. S-(+)-Carvone was transformed into the phenanthrenone 2a in six steps (53% overall yield), using an intramolecular Diels-Alder reaction as the key step. Conversion of the enone function in 2a into an epoxyaldehyde function followed by cyclisation and aromatisation in acid conditions completed the construction of ring D.
ChemInform Abstract: Conjugate Addition of Organolithium Reagents to α,β-Unsaturated Carboxylic Acids.
Abstract Conjugate addition of primary, secondary, tertiary alkyl and phenyl lithium reagents to 2-alkenoic acids affords good yields of branched saturated carboxylic acids. Methyl groups at the α- and β-carbon of the 2-alkenoic acid decrease reactivity as acceptors, and foster deprotonation, respectively. The lithium enediolate resulting from the conjugate addition can react with electrophiles. PM3 calculations are in agreement with the substituent effects.
Understanding the cooperative NHC/LA catalysis for stereoselective annulation reactions with homoenolates. A DFT study.
The role of Ti(Oi-Pr)(4) Lewis acid (LA) in the cooperative N-heterocyclic carbene (NHC)/LA catalyzed addition of enals to enones to yield cis-cyclopentenes has been investigated using DFT methods at the B3LYP/6-31G** computational level. Ti(IV) effectively catalyzes the reaction by formation of a complex with cinnamaldehyde 1, which favors the nucleophilic attack of NHC 5 on 1, and the subsequent proton abstraction to yield the extended Ti(IV)-Breslow intermediate 21. The nature of the metal involved in the LA catalyst plays a relevant role due to the more basic character of NHCs than aldehydes. Thus, strong LAs, such as Zn(OTf)(2), prevent the catalytic behavior of NHCs to form a very sta…
Synthesis, Optical Properties, and DNA Interaction of New Diquats Based on Triazolopyridines and Triazoloquinolines
New diquat derivatives based on [1,2,3]triazolo[1,5-a]pyridine and [1,2,3]triazolo[1,5-a]quinoline have been synthesized in excellent yields. To evaluate the effect of the alkyl bridge length, ethane and propane dibromo alkane substrates were used for their synthesis. Theoretical calculations predicted a very small energetic barrier between the two possible enantiomers P (Ra ) and M (Sa ), which makes them very difficult to resolve. Thermal denaturation studies, UV/Visible spectroscopy, and fluorescence titrations with ct-DNA evidenced the intercalation of the quinoline derivatives in DNA.
Understanding the Participation of Quadricyclane as Nucleophile in Polar [2σ + 2σ + 2π] Cycloadditions toward Electrophilic π Molecules
The formal [2sigma + 2sigma + 2pi] cycloaddition of quadricyclane, 1, with dimethyl azodicarboxylate, 2, in water has been studied using DFT methods at the B3LYP/6-31G** and MPWB1K/6-31G** levels. In the gas phase, the reaction of 1 with 2 has a two-stage mechanism with a large polar character and an activation barrier of 23.2 kcal/mol. Inclusion of water through a combined discrete-continuum model changes the mechanism to a two-step model where the first nucleophilic attack of 1 to 2 is the rate-limiting step with an activation barrier of 14.7 kcal/mol. Analysis of the electronic structure of the transition state structures points out the large zwitterionic character of these species. A DF…
A Short and Improved Synthesis of the Antiprotozoal Abietane Diterpenoid (–)-Sugikurojin A
An efficient and straightforward semisynthesis of the antiprotozoal abietane diterpenoid (–)-sugikurojin A, starting from the readily available methyl ester of callitrisic acid (4-epi-dehydroabietic acid) isolated from sandarac resin, is reported. This optimized semisynthetic route provides a convenient source of the antiprotozoal compound, in four steps from methyl callitrisate in 50% overall yield, for further biological studies.
CONVERSION OF RESIN ACIDS INTO STEROIDAL COMPOUNDS. A REVIEW
(1991). CONVERSION OF RESIN ACIDS INTO STEROIDAL COMPOUNDS. A REVIEW. Organic Preparations and Procedures International: Vol. 23, No. 3, pp. 321-356.
Toward an Understanding of the Mechanisms of the Intramolecular [5 + 2] Cycloaddition Reaction of γ-Pyrones Bearing Tethered Alkenes. A Theoretical Study
The molecular mechanism for the intramolecular [5 + 2] cycloaddition reaction of β-silyloxy-γ-pyrones bearing tethered alkenes has been characterized using ab initio methods. A comparative study for this sort of cycloaddition carried out at different computational levels points out that the B3LYP/6-31G* calculations give similar barriers to those obtained with the MP3/6-31G* level. Analysis of the energetic results shows that the reaction takes place along a stepwise process: first, the migration of the neighboring silyl group to the carbonyl group of the γ-pyrone takes place to give a weak oxidopyrylium ylide intermediate, which by a subsequent concerted intramolecular [5 + 2] cycloadditi…
A DFT study of the asymmetric (S)-5-(pyrrolidin-2-yl)-1H-tetrazole catalyzed Michael addition of carbonyl compounds to nitroalkenes
Abstract The role of the ( S )-5-(pyrrolidin-2-yl)-1 H -tetrazole in the asymmetric organocatalyzed Michael addition of carbonyl compounds to nitroalkenes has been studied using DFT methods at the B3LYP/6-31G ∗∗ computational level. For the C–C bond-formation step, several reactive channels have been analyzed. The B3LYP/6-31G ∗∗ results, which are in reasonable agreement with the experiments, allow us to explain the stereoselectivity and the increase of the reactivity achieved by an intramolecular HB between the acid hydrogen of the tetrazole moiety and one oxygen atom of the nitroalkene.
Empirical modeling of material composition and size in MOFs prepared with ligand mixtures
Systematic analyses of the composition and size of metal-organic frameworks built with Zn4O and terephthalic/amino-terephthalic acid mixtures, together with a kinetic assay, reveal how these ligands behave differently, which reveals the complexity of crystal growth in these frameworks and the ability to tune it on purpose.
Understanding the Mechanism of the Intramolecular Stetter Reaction. A DFT Study
The mechanism of the N-heterocyclic carbene (NHC)-catalyzed intramolecular Stetter reaction of salicylaldehyde 1 to yield chromanone 3 has been theoretically studied at the B3LYP/6-31G** level. This NHC-catalyzed reaction takes place through six elementary steps, which involve: (i) formation of the Breslow intermediate IN2; (ii) an intramolecular Michael-Type addition in IN2 to form the new C-C s bond; and (iii) extrusion of the NHC catalyst from the Michael adduct to yield chromanone 3. Analysis of the relative free energies in toluene indicates that while formation of Breslow intermediate IN2 involves the rate-determining step of the catalytic process, the intramolecular Michael-type addi…
ChemInform Abstract: Diastereoselective Synthesis of Spongian Diterpenes. Total Synthesis of the Furanoditerpene (-)-Spongia-13(16),14-diene.
Abstract An effective diastereoselective synthesis of the marine-sponge metabolite (−)-spongia-13(16),14-diene 1 is achieved starting from S-(+)-carvone via a homochiral phenanthrenone as the key intermediate for the construction of the furan ring system. S-(+)-Carvone was transformed into the phenanthrenone 2a in six steps (53% overall yield), using an intramolecular Diels-Alder reaction as the key step. Conversion of the enone function in 2a into an epoxyaldehyde function followed by cyclisation and aromatisation in acid conditions completed the construction of ring D.
Assignment of1H and13C NMR data for (−)-methyl thyrsiflorin A and some scopadulan precursors
The 1H and 13C NMR spectral analysis of synthetic (−)-methylthyrsiflorin A and 10 scopadulan precursors is reported. Resonance assignments were based on one- and two-dimensional NMR techniques, which included 1H, 13C, DEPT and HMQC and also 1D NOE difference spectroscopy. Copyright © 2001 John Wiley & Sons, Ltd.
Acceptorless dehydrogenative condensation: synthesis of indoles and quinolines from diols and anilines.
The use of diols and anilines as reagents for the preparation of indoles represents a challenge in organic synthesis. By means of acceptorless dehydrogenative condensation, heterocycles, such as indoles, can be obtained. Herein we present an experimental and theoretical study for this purpose employing heterogeneous catalysts Pt/Al2O3 and ZnO in combination with an acid catalyst (p-TSA) and NMP as solvent. Under our optimized conditions, the diol excess has been reduced down to 2 equivalents. This represents a major advance, and allows the use of other diols. 2,3-Butanediol or 1,2-cyclohexanediol has been employed affording 2,3-dimethyl indoles and tetrahydrocarbazoles. In addition, 1,3-pro…
ChemInform Abstract: Toward an Understanding of the Mechanisms of the Intramolecular [5 + 2] Cycloaddition Reaction of γ-Pyrones Bearing Tethered Alkenes. A Theoretical Study.
The molecular mechanism for the intramolecular [5 + 2] cycloaddition reaction of β-silyloxy-γ-pyrones bearing tethered alkenes has been characterized using ab initio methods. A comparative study for this sort of cycloaddition carried out at different computational levels points out that the B3LYP/6-31G* calculations give similar barriers to those obtained with the MP3/6-31G* level. Analysis of the energetic results shows that the reaction takes place along a stepwise process: first, the migration of the neighboring silyl group to the carbonyl group of the γ-pyrone takes place to give a weak oxidopyrylium ylide intermediate, which by a subsequent concerted intramolecular [5 + 2] cycloadditi…
Understanding the mechanism of stereoselective synthesis of cyclopentenes via N-heterocyclic carbene catalyzed reactions of enals with enones.
The N-heterocyclic carbene (NHC) catalyzed addition of enals to enones to yield trans-cyclopentenes has been investigated using DFT methods at B3LYP/6-31G** computational level. This NHC catalyzed reaction comprises several steps. The first one is the formation of a Breslow intermediate, which nucleophilically attacks to the conjugated position of the enone to yield an enol-enolate. This second step is responsible for the trans relationship at the final cyclopentene. An intramolecular aldolic condensation allows for the formation of the alkoxy cyclopentane intermediate, that by intramolecular nucleophilic attack on the carbonyl group yields a bicyclic ether. The extrusion of the NHC catalys…
A theoretical study of the selectivity for the domino [5+2]/[4+2] cycloadditions of γ-pyrones bearing tethered alkenes with substituted 1,3-butadienes
Abstract Selectivity of the domino [5+2]/[4+2] cycloaddition reactions of a β-silyloxy-γ-pyrone bearing a tethered alkene with two substituted 1,3-butadienes have been theoretically studied at the B3LYP/6-31G∗//AM1 and B3LYP/6-31G∗ computational levels. Analysis of these results allow explaining the regio, stereo and chemoselectivity observed experimentally at these domino reactions. Selectivity outcome is reproduced by these calculations.
An approach to erythrophleum alkaloids. Synthesis of methyl (−)-4-epi-cassamate
Abstract A synthetic approach to Erythrophleum alkaloids, involving as a key-step the regiospecific deprotonation of the ketone 5a, is described.
Stereostructural revision of auricularic acid synthesis of 4-epi-auricularic acid
Abstract Cleistanth-13,15-dien-18-oic acid (1) has been synthesised from methyl 13-keto-podocarp-8(14)-en-18-oate (3). It is demonstrated that auricularic acid is an epimer at C-4 of 1, so it must be reformulated as cleistanth-13,15-dien-19-oic acid (2).
Density functional theory study of the 5-pyrrolidin-2-yltetrazole-catalyzed aldol reaction
Abstract The replacement of the carboxylic acid functionality with a tetrazolic acid in the proline-catalyzed asymmetric aldol reaction between acetone and trimethylacetaldehyde has been studied using DFT methods at the B3LYP/6-31G** computational level. For the C–C bond-formation step, four reactive channels corresponding to the syn and anti arrangement of the enamine and the re and si attack modes have been analyzed. The B3LYP/6-31G** results allowed us to explain the stereoselectivity and the increase in reactivity relative to the proline-catalyzed process in DMSO.
ChemInform Abstract: Synthesis of (-)-Auricularic Acid and its C-4 Epimer. The Absolute Configuration of Auricularic Acid.
Abstract A synthesis of (−)-auricularic acid (2a) starting from methyl (+)-13-oxo- podocarp-8(14)-en-19-oate (3a) and a synthesis of its C-4 epimer (2b) starting from methyl (+)-13-oxopodocarp-8(14)-en-18-oate (3b) are described. The absolute configuration of natural auricularic acid is stablished as (4R, 5S, 8S, 9R, 10S, 14S).
An Efficient Stereoselective Synthesis of Stypodiol and Epistypodiol
An efficient synthesis of stypodiol (1) and its epimer at C-14, epistypodiol (2), was accomplished starting from (S)-(+)-carvone (7). The synthesis of both epimeric compounds proceeds through common intermediates using an IMDA reaction, a sonochemical Barbier reaction, and an acid-catalyzed quinol−tertiary alcohol cyclization as key synthetic steps.
1H and13C NMR assignments and conformational analysis of some podocarpene derivatives
This paper reports on the assignment of the 1 Ha nd 13 C NMR spectra of five podocarpene derivatives. Resonance assignments were made on the basis of one- and two-dimensional NMR techniques which included 1 H, 13 C, DEPT and HMQC and also 1D NOE difference spectroscopy. The ratio of the different conformers in the six- membered C-ring of the podocarpene system was determined by molecular mechanics calculations and analysis of proton spin-spin coupling constants. Copyright © 2000 John Wiley & Sons, Ltd.
Structural study of oxalamide compounds: 1H, 13C, and DFT calculations
Abstract The conformational properties of some N-alkyl, N,N′-dialky, and tetraalkyloxalamides have been investigated, in vacuo and in solvent using DFT methods at the B3LYP/6-31G∗∗ computational level. Special emphasis has been given on oxalamides with substituents of the type –CH2CH2OH. In oxalamides with the N–H group (N-alkyl and N,N′-dialky), the most stable conformations are those in which the oxalamide moiety adopts a planar s-trans arrangement and the amide bonds are trans. A different situation appears in the case of tetraalkyloxalamides, in which the oxalamide moiety always adopts a skewed arrangement and there are conformations with similar energy. A careful study of 13C and 1H NM…
Synthesis of C-17-functionalized spongiane diterpenes: diastereoselective synthesis of (-)-spongian-16-oxo-17-al, (-)-acetyldendrillol-1, and (-)-aplyroseol-14.
The diastereoselective synthesis of spongiane diterpenes (-)-spongian-16-oxo-17-al 2, (-)-acetyldendrillol-1 15, and (-)-aplyroseol-14 16 has been completed efficiently via the common intermediate 14. Compound 14 was prepared in five synthetic steps from (+)-podocarp-8(14)-en-13-one 13, easily available from commercial (-)-abietic acid. The key steps in the syntheses were a regioselective reduction of a 1,4-dialdehyde unit, a one-pot acetalization-acetylation, and a translactonization. The synthesis of 15 and 16 has led us to a revision of the configuration at C-17 for natural (-)-acetyldendrillol-1 and a structural reassignment for aplyroseol-14. Thus, aplyroseol-14 16 presents an unpreced…
The role of the transfer group in the intramolecular [5+2] cycloadditions of substituted β-hydroxy-γ-pyrones: a DFT analysis
The intramolecular [5+2] cycloaddition reactions of a series of 3-OR (R=SiMe3, H, CHO, Me) substituted β-hydroxy-γ-pyrones bearing tethered alkenes were studied using DFT methods at the B3LYP/6–31G* level. The role of the transfer R group was analyzed considering two alternative channels: (i) in channel a the process is initialized by the transfer of the R group with formation of an oxidopyrylium ylide intermediate, which is followed of an intramolecular [5+2] cycloaddition; (ii) in channel b, the process is initialized by the intramolecular [5+2] cycloaddition on the γ-pyrone followed by the transfer of the R group. Copyright © 2005 John Wiley & Sons, Ltd.
1H and13C NMR assignments and conformational analysis of some tetracyclic compounds with a bicyclo[4.2.0]octane ring system
A new mechanism for internal nucleophilic substitution reactions
A new mechanism for the classic internal nucleophilic substitution reactions SNi by means of computational studies in the gas-phase, DCM and acetonitrile is reported. Despite the importance of the SNi mechanism, since the mid-1990s this mechanism has remained unexplored. This study focused mainly on the comparison between the mechanisms postulated to date for the SNi reactions and a new mechanism suggested by us that fits better the experimental observations. This comparative study has been applied to the conversion of ethyl, neopentyl, isopropyl and tert-butyl chlorosulfites into the corresponding alkyl chlorides. This new mechanism occurs through two transition structures. For primary and…
Conjugate addition of organolithium reagents to α,β-unsaturated carboxylic acids
Abstract Conjugate addition of primary, secondary, tertiary alkyl and phenyl lithium reagents to 2-alkenoic acids affords good yields of branched saturated carboxylic acids. Methyl groups at the α- and β-carbon of the 2-alkenoic acid decrease reactivity as acceptors, and foster deprotonation, respectively. The lithium enediolate resulting from the conjugate addition can react with electrophiles. PM3 calculations are in agreement with the substituent effects.
ChemInform Abstract: A Theoretical Study of the Selectivity for the Domino [5 + 2]/[4 + 2] Cycloadditions of γ-Pyrones Bearing Tethered Alkenes with Substituted 1,3-Butadienes.
Abstract Selectivity of the domino [5+2]/[4+2] cycloaddition reactions of a β-silyloxy-γ-pyrone bearing a tethered alkene with two substituted 1,3-butadienes have been theoretically studied at the B3LYP/6-31G∗//AM1 and B3LYP/6-31G∗ computational levels. Analysis of these results allow explaining the regio, stereo and chemoselectivity observed experimentally at these domino reactions. Selectivity outcome is reproduced by these calculations.
A theoretical study on NHC-catalysed enantioselective cycloaddition of ketenes and 3-aroylcoumarins: mechanism and enantioselectivity.
NHC-catalysed enantioselective cycloaddition of ketenes to 3-aroylcoumarins to yield dihydrocoumarin-fused dihydropyranones has been investigated using DFT methods at the B3LYP/6-31G* and MPWB1K/6-311G** computational levels. Two plausible mechanisms have been studied: the “ketene-first” mechanism A and the “coumarin-first” mechanism B. An analysis of the activation Gibbs free energies involved in the two competitive pathways makes it possible to rule out the pathway associated with the “coumarin-first” mechanism B. The first step of the “ketene-first” mechanism A is the formation of zwitterionic intermediate IN1-Zvia a nucleophilic attack of NHC 1 on ketene 2. A [4 + 2] cycloaddition throu…
Synthesis and antiviral activity of scopadulcic acids analogues
The synthesis and antiviral properties of several scopadulcic acid analogues functionalized at C-6/C-7 and C-13 is reported. The preparation of advanced intermediates for the synthesis of scopadulcic acid B/scopadulciol analogues is also described. The biological study revealed the importance of polar groups at C-13, while the stereochemistry at C-8 was not critical for activity.
Toward an Understanding of the Molecular Mechanism of the Reaction between 1-Methylpyrrole and Dimethyl Acetylenedicarboxylate. An ab Initio Study
The molecular mechanism for the reaction between 1-methylpyrrole and dimethyl acetylenedicarboxylate (DMAD) has been studied using ab initio methods. Two alternative reaction pathways have been considered, both of which correspond to stepwise processes with initial, rate-determining formation of a common zwitterionic intermediate. This intermediate is formed by nucleophilic attack of the pyrrole ring to the carbon−carbon triple bond of DMAD. Closure of this intermediate (pathway A) affords a [4 + 2] cycloadduct, whereas intramolecular proton transfer (pathway B) affords a Michael adduct. The much larger potential energy barrier of the second step in pathway B relative to pathway A is respon…
The nucleophilic addition of nitrones to carbonyl compounds: insights on the nature of the mechanism of the l-proline induced asymmetric reaction from a DFT analysis
Abstract The mechanism of the l -proline induced asymmetric nitrone–aldol reaction of N -methyl- C -ethylnitrone with dimethyl ketomalonate has been studied by using density functional theory at B3LYP/6-31G** level. The reaction was initialized by the addition of l -proline to the nitrone to form an aminal, which by elimination of the hydroxylamine gave a chiral enamine. The nucleophilic addition of this chiral enamine to dimethyl ketomalonate corresponds to stereoselective C–C bond-formation step. Further nucleophilic addition of hydroxylamine to the zwitterionic intermediate formed in the enamine addition gave a second aminal, which by l -proline elimination afforded the corresponding β-h…
Translocation versus cyclisation in radicals derived from N-3-alkenyl trichloroacetamides
Under radical reaction conditions, two different and competitive reaction pathways were observed for N-(alpha-methylbenzyl)trichloroacetamides with a N-3-cyclohexenyl substituent: 1,4-hydrogen translocation and radical addition to a double bond. However, for radicals with an acyclic alkenyl side chain, the direct cyclisation process was exclusively observed. The dichotomy between translocation and direct radical cyclisation in these substrates has been theoretically studied using density functional theory (DFT) methods at the B3LYP/6-31G** computational level.
1H and 13C NMR signal assignment of synthetic (-)-methyl thyrsiflorin B acetate, (-)-thyrsiflorin C and several scopadulane derivatives.
The 1H and 13C NMR signal assignment of the data of 13 scopadulane-type diterpenes is reported. It was based on one- and two- dimensional NMR techniques which included 1H, 13C, DEPT, HMQC and 1D NOE difference spectroscopy. Copyright © 2005 John Wiley & Sons, Ltd.
ChemInform Abstract: Conversion of Resin Acids into Steroidal Compounds. A Review
(1991). CONVERSION OF RESIN ACIDS INTO STEROIDAL COMPOUNDS. A REVIEW. Organic Preparations and Procedures International: Vol. 23, No. 3, pp. 321-356.
About the relevance of anion-π interactions in water.
Anion-π interactions are emerging as exotic features with potential applications in chemistry. In the last years, their relevance in living systems has been outlined, and so far there is no concluding significant evidence recognized about the participation of anion-π interactions in water because anion-π sensors contain large aromatic hydrophobic surfaces with limited solubility. By transforming a neutral heterocycle (for example quinoline) into its corresponding salt (quinolinium), we have been able to overcome these solubility issues, and new cationic water-soluble fluorophores have been prepared. Herein, we used N-alkylated heterocycles as π-acidic surfaces to shed light on the nature of…
Semisynthesis of the Antiviral Abietane Diterpenoid Jiadifenoic Acid C from Callitrisic Acid (4-Epidehydroabietic Acid) Isolated from Sandarac Resin
The semisynthesis of the antiviral abietane diterpenoid (+)-jiadifenoic acid C starting from the available methyl ester of callitrisic acid (4-epidehydroabietic acid) isolated from sandarac resin is reported. A protocol for the isolation of methyl callitrisate (methyl 4-epidehydroabietate) in gram quantities from sandarac resin is also described. Allylic C-17 oxygenation was introduced by regioselective dehydrogenation of the isopropyl group of methyl callitrisate with DDQ followed by selenium-catalyzed allylic oxidation. Ester hydrolysis afforded (+)-jiadifenoic acid C in 22% overall yield from methyl callitrisate. This semisynthetic route provides a convenient source of this anti-Coxsacki…
First Diastereoselective Synthesis of (−)-Methyl Thyrsiflorin A, (−)-Methyl Thyrsiflorin B Acetate, and (−)-Thyrsiflorin C
An efficient procedure for the synthesis of scopadulan diterpenes, using (+)-podocarp-8(14)-en-13-one 13 as starting material, is reported. This procedure has been used for the diastereoselective synthesis of (-)-methyl thyrsiflorin A (8), (-)-methyl thyrsiflorin B acetate (9), and (-)-thyrsiflorin C (7). Key steps in our strategy are the intramolecular cyclopropanation of diazoketone 19 and the regioselective cleavage of the cyclopropane ring.
Synthesis and cytotoxic activity of novel C7-functionalized spongiane diterpenes.
Based on two lead cytotoxic spongiane diterpenes, a new series of C7-oxygenated derivatives were synthesized and evaluated for their antitumor activity in vitro against the cancer cell lines HeLa and HEp-2. In general, introduction of either hydroxyl or acetoxy groups at C-7 did not improve the resultant cytotoxicity, while the presence of a butyrate ester led to more active compounds (CC(50)=4.0-9.5 microM).
Reactivity difference between diphosgene and phosgene in reaction with (2,3-anti)-3-amino-1,2-diols
In reactions of (2,3-anti)-3-amino-1,2-diols with diphosgene and phosgene and their conversion into 1,3-oxazolidin-2-ones, some differences in the stereochemistry of the reactions have been found with these two reagents. The reactions with phosgene afforded the expected cis-oxazolidinones, and in the reaction with diphosgene under the same reaction conditions, the trans-oxazolidinones were also obtained.
Evaluation of Superparamagnetic Silica Nanoparticles for Extraction of Triazines in Magnetic in-Tube Solid Phase Microextraction Coupled to Capillary Liquid Chromatography
The use of magnetic nanomaterials for analytical applications has increased in the recent years. In particular, magnetic nanomaterials have shown great potential as adsorbent phase in several extraction procedures due to the significant advantages over the conventional methods. In the present work, the influence of magnetic forces over the extraction efficiency of triazines using superparamagnetic silica nanoparticles (NPs) in magnetic in tube solid phase microextraction (Magnetic-IT-SPME) coupled to CapLC has been evaluated. Atrazine, terbutylazine and simazine has been selected as target analytes. The superparamagnetic silica nanomaterial (SiO2-Fe3O4) deposited onto the surface of a capil…
Unzipping Nucleoside Channels by Means of Alcohol Disassembly
Gold nanoparticles capped with simple adenosine derivatives can form colloidal aggregates in nonpolar solvents. Theoretical calculations indicate the formation of organic channels by the supramolecular assembly of the nanoparticles by means of hydrogen bonds between the adenine moieties. The aggregates were only negligibly sensitive to nPrOH, iPrOH, and tBuOH, whereas some showed a similar response to MeOH and EtOH, and others showed high selectivity toward MeOH. DNA nucleoside derivatives (1-(2-deoxy-β-D-ribofuranosyl)-5-methyluracil and 2′,3′-O-isopropylideneadenosine) as well as thymine and other aromatic compounds such as pyrene derivatives (pyrene, 1-chloropyrene, 1-hydroxypyrene, (1-p…
Acetylcholinesterase and antioxidant evaluation of C18-functionalized ferruginol analogues
Nearly 200 years ago, the study of the chemistry of terpenoids started with the analysis of turpentine oil, investigating the first resin acid, abietic acid from pine oleoresin.[1] Abietic acid occurs in plants of the genus Abies and is the first member of a class of plant metabolites, the abietane-type diterpenoids. They are characterized by a tricyclic ring system and have shown a wide range of chemical diversity and biological activity. [2,3] Medicinal chemists have studied derivatives of two readily available materials such as dehydroabietic acid and dehydroabietylamine. [3] To date, there is only one commercial drug, Ecabet® [ecabet sodium], based on abietanes, which is used for the tr…
Biological Profiling of Semisynthetic C19-Functionalized Ferruginol and Sugiol Analogues
[EN] The abietane-type diterpenoids are significant bioactive compounds exhibiting a varied range of pharmacological properties. In this study, the first synthesis and biological investigation of the new abietane-diterpenoid (+)-4-epi-liquiditerpenoid acid (8a) together with several of its analogs are reported. The compounds were generated from the readily available methyl callitrisate (7), which was obtained from callitrisic acid present in Moroccan Sandarac resin. A biological evaluation was conducted to determine the effects of the different functional groups present in these molecules, providing basic structure-activity relationship (SAR) elements. In particular, the ferruginol and sugi…
Experimental and DFT study of the conversion of ephedrine derivatives into oxazolidinones. Double SN2 mechanism against SN1 mechanism
Sulfonation of the N-Boc derivatives of 1,2-aminoalcohols, such as ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, thiomicamine, and chloramphenicol yields a mixture of the corresponding oxazolidinones with inversion (erythro derivatives) and/or retention of configuration (threo derivatives)at C5. We suggest a competition between two mechanisms: an intramolecular SN2 process initiated by attack of the carbonyl oxygen of the Boc group to the benzylic carbon and the other one through a double SN2 process. In the erythro derivatives the first mechanism is predominant, while in the threo derivatives both mechanisms have similar energy. This hypothesis is supported by theoretical c…
13C nuclear magnetic resonance spectra of several podocarpane and cassane diterpenoids
The 13C NMR spectra of several diterpenic derivatives having the podocarpane and cassane skeleton were recorded and interpreted. The most significant effects due to substituent orientation, B/C ring junction stereochemistry and conformational changes are briefly discussed.
Lewis Acid Induced [2+2] Cycloadditions of Silyl Enol Ethers with α,β-Unsaturated Esters: A DFT Analysis
The Lewis acid (LA) induced cycloaddition of trimethysilyl vinyl ether with methyl acrylate has been studied by DFT methods at the B3LYP/6-31G* level. In the absence of an LA, a [4+2] cycloaddition between the silyl enol ether and methyl acrylate in the s-cis conformation takes place through an asynchronous, concerted bond-formation process. This cycloaddition presents a large activation enthalpy of 21.1 kcal mol–1. Coordination of the LA AlCl3 to the carbonyl oxygen atom of methyl acrylate yields a change of molecular mechanism from a concerted to a two-step mechanism and produces a drastic reduction of the activation energy. This stepwise mechanism is initialized by the nucleophilic attac…
Synthesis of bodinieric acids A and B, both C-18 and C-19-functionalized abietane diterpenoids: DFT study of the key aldol reaction
[EN] The first synthesis of C-18- and C-19-bifunctionalized abietane diterpenoids, bodinieric (or callicapoic) acids, via an aldol reaction has been developed. This key aldol reaction was very sensitive to steric hindrance. This fact has been studied by deuterium exchange experiments and DFT methods. Optimization of this reaction led to the synthesis of anti-inflammatory bodinieric acids A and B, starting from abietic acid
Reactivity of β-amino alcohols against dialkyl oxalate: synthesis and mechanism study in the formation of substituted oxalamide and/or morpholine-2,3-dione derivatives
The reactivity of various β-amino alcohols with dialkyl oxalates, in several reaction conditions, has been investigated. Linear disubstituted oxalamides were obtained with primary β-amino alcohols and linear tetrasubstituted oxalamides, or a mixture of linear tetrasubstituted oxalamides and cyclic morpholine-2,3-diones were obtained with N-substituted β-amino alcohols. A DFT study of the possible mechanism has been made. The theoretical results indicate that these reactions are not kinetically controlled, there is an equilibrium between all species and therefore follow a thermodynamic control. The different behavior between the primary β-amino alcohols and N-methyl β-amino alcohols is due t…
CCDC 1939485: Experimental Crystal Structure Determination
Related Article: Javier Pitarch-Jarque, Ramón J. Zaragozá, Rafael Ballesteros, Belen Abarca, Enrique Garcia-España, Begoña Verdejo, Rafael Ballesteros-Garrido|2021|Dalton Trans.|50|6834|doi:10.1039/D1DT00771H
CCDC 1939483: Experimental Crystal Structure Determination
Related Article: Javier Pitarch-Jarque, Ramón J. Zaragozá, Rafael Ballesteros, Belen Abarca, Enrique Garcia-España, Begoña Verdejo, Rafael Ballesteros-Garrido|2021|Dalton Trans.|50|6834|doi:10.1039/D1DT00771H
CCDC 1939484: Experimental Crystal Structure Determination
Related Article: Javier Pitarch-Jarque, Ramón J. Zaragozá, Rafael Ballesteros, Belen Abarca, Enrique Garcia-España, Begoña Verdejo, Rafael Ballesteros-Garrido|2021|Dalton Trans.|50|6834|doi:10.1039/D1DT00771H