585. The stereochemistry of the adducts of p-benzoquinone with two molecules of cyclopentadiene. Charge-transfer from olefinic double bonds to p-benzoquinone and ene-1,4-dione groups
Abstract:The endo-trans-endo-configuration of the biscyclopentadiene-benzoquinone adduct has been established by photochemical cyclisation, in agreement with Winstein's conclusions. p-Benzoquinones and ene-1,4-diones with olefinic double bonds overlapping the chromophore show a new band in the ultraviolet spectrum, not present in that of the parent chromophore, attributed to intramolecular charge-transfer. The medium-wavelength band in the spectrum of p-benzoquinones is very sensitive to the effects of strain.AN intere… Show more
“…X-ray crystal structure analyses 37 show both adducts, 18a and 24 , to be of endo - trans - endo -configuration. This is in agreement with results of the double-side addition of p -benzoquinone with cyclopentadiene, which also show the endo - trans - endo -configuration in the cycloadduct because of steric and electronic factors . Hydrogenation of 18a with H 2 (Pd/C) gives 18b as the single product, where the double bond of the norbornene unit is hydrogenated exclusively, and not the olefinic bond of the thiabicyclo[2.2.1]heptene oxide moiety (Figure ). 6 t…”
Thiophenes 1 were treated with m-chloroperbenzoic acid (m-CPBA) under BF(3).Et(2)O catalysis to afford thiophene S-monoxides. These could be reacted in situ as intermediary species with a number of dienophiles to provide arenes (with alkynes as dienophiles) or 7-thiabicyclo[2.2.1]hept-2-ene 7-oxides (with alkenes as dienophiles). It was also possible to isolate thiophene S-monoxides in solution and to cycloadd them in a second step. In either way it could be shown that the use of BF(3).Et(2)O enhances the yields of the oxidative cycloaddition of thiophenes considerably. Moreover a greater variety of dienophiles (29a, 29b, 29c) could be reacted with thiophenes than in the case of the noncatalyzed reaction. All cycloadditions catalyzed by BF(3).Et(2)O give only a single diastereoisomer as cycloadduct. The reactions show a high pi-facial selectivity, a fact that can be explained by the Cieplak-effect. Without added dienophiles, 2-methylthiophene (1e) gave a single dimer (36) of 2-methylthiophene S-monoxide, whereas 2,5-dimethylthiophene (1a) gave three dimers (32a-c). In the case of tetrasubstituted thiophenes, thiophene S-monoxides (e.g., 31b and 31c) could be isolated in substance.
“…X-ray crystal structure analyses 37 show both adducts, 18a and 24 , to be of endo - trans - endo -configuration. This is in agreement with results of the double-side addition of p -benzoquinone with cyclopentadiene, which also show the endo - trans - endo -configuration in the cycloadduct because of steric and electronic factors . Hydrogenation of 18a with H 2 (Pd/C) gives 18b as the single product, where the double bond of the norbornene unit is hydrogenated exclusively, and not the olefinic bond of the thiabicyclo[2.2.1]heptene oxide moiety (Figure ). 6 t…”
Thiophenes 1 were treated with m-chloroperbenzoic acid (m-CPBA) under BF(3).Et(2)O catalysis to afford thiophene S-monoxides. These could be reacted in situ as intermediary species with a number of dienophiles to provide arenes (with alkynes as dienophiles) or 7-thiabicyclo[2.2.1]hept-2-ene 7-oxides (with alkenes as dienophiles). It was also possible to isolate thiophene S-monoxides in solution and to cycloadd them in a second step. In either way it could be shown that the use of BF(3).Et(2)O enhances the yields of the oxidative cycloaddition of thiophenes considerably. Moreover a greater variety of dienophiles (29a, 29b, 29c) could be reacted with thiophenes than in the case of the noncatalyzed reaction. All cycloadditions catalyzed by BF(3).Et(2)O give only a single diastereoisomer as cycloadduct. The reactions show a high pi-facial selectivity, a fact that can be explained by the Cieplak-effect. Without added dienophiles, 2-methylthiophene (1e) gave a single dimer (36) of 2-methylthiophene S-monoxide, whereas 2,5-dimethylthiophene (1a) gave three dimers (32a-c). In the case of tetrasubstituted thiophenes, thiophene S-monoxides (e.g., 31b and 31c) could be isolated in substance.
“…The cage lactone ( 2 ) [ 18 ] was synthesized from Cooksen’s dione [ 46 , 47 ] using a reported procedure utilizing sodium cyanide to generate cyano cage lactam which was converted to cage lactone ( 2 ) using hydrochloric acid (Scheme 1 ). Scheme 1 Synthesis of the cage lactone (i) NaCN, CH3COOH, H2O (ii) 3 M HCl.…”
BackgroundNovel pentacycloundecane (PCU)-lactone-CO-EAIS peptide inhibitors were designed, synthesized, and evaluated against wild-type C-South African (C-SA) HIV-1 protease. Three compounds are reported herein, two of which displayed IC50 values of less than 1.00 μM. A comparative MM-PB(GB)SA binding free energy of solvation values of PCU-lactam and lactone models and their enantiomers as well as the PCU-lactam-NH-EAIS and lactone-CO-EAIS peptide inhibitors and their corresponding diastereomers complexed with South African HIV protease (C-SA) was performed. This will enable us to rationalize the considerable difference between inhibitory concentration (IC50) of PCU-lactam-NH-EAIS and PCU-lactone-CO-EAIS peptides.ResultsThe PCU-lactam model exhibited more negative calculated binding free energies of solvation than the PCU-lactone model. The same trend was observed for the PCU-peptide inhibitors, which correspond to the experimental activities for the PCU-lactam-NH-EAIS peptide (IC50 = 0.076 μM) and the PCU-lactone-CO-EAIS peptide inhibitors (IC50 = 0.850 μM). Furthermore, a density functional theory (DFT) study on the natural atomic charges of the nitrogen and oxygen atoms of the three PCU-lactam, PCU-lactim and PCU-lactone models were performed using natural bond orbital (NBO) analysis. Electrostatic potential maps were also used to visualize the electron density around electron-rich regions. The asymmetry parameter (η) and quadrupole coupling constant (χ) values of the nitrogen and oxygen nuclei of the model compounds were calculated at the same level of theory. Electronic molecular properties including polarizability and electric dipole moments were also calculated and compared. The Gibbs theoretical free solvation energies of solvation (∆Gsolv) were also considered.ConclusionsA general trend is observed that the lactam species appears to have a larger negative charge distribution around the heteroatoms, larger quadrupole constant, dipole moment and better solvation energy, in comparison to the PCU-lactone model. It can be argued that these characteristics will ensure better eletronic interaction between the lactam and the receptor, corresponding to the observed HIV protease activities in terms of experimental IC50 data.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-015-0115-5) contains supplementary material, which is available to authorized users.
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