ChemInform Abstract: Synthesis of 4-Aminocyclohex-1-enecarboxylates from Danishefsky′s Diene (original) (raw)
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The Journal of Organic Chemistry, 2008
Thionyl chloride (SOCl 2 ) acts as halogenation reagent in its reaction with 1-[phenyl(hydroxy)methyl]-2-R-1,2-dicarbacloso-dodecaborane 1a,b but unexpectedly behaves as an oxidant for 1-[2′-pyridyl(hydroxy)methyl]-2-R-1,2-dicarbacloso-dodecaboranes 2a,b. The synthesis and characterization of all new compounds, including structure determinations of 1a, 2a, 1-[phenyl(chloro)methyl]-2-methyl-1,2-dicarbacloso-dodecaborane 3a, and 1-[2′-pyridyl(oxo)methyl]-2methyl-1,2-dicarba-closo-dodecaboranes 4a are reported and the possible pathways are discussed.
C 60 -Based Triads with Improved Electron-Acceptor Properties: Pyrazolylpyrazolino[60]fullerenes †
The Journal of Organic Chemistry, 2001
A series of triad pyrazolylpyrazolino[60]fullerenes has been prepared in one pot from suitably functionalized hydrazones by 1,3-dipolar cycloaddition reactions under microwave irradiation. The electrochemical properties of the compounds obtained were investigated by cyclic voltammmetry, and they show better electron acceptor character than the parent C 60 in all cases. Fluorescence experiments and time-resolved transition spectroscopy indicate the existence of photoinduced chargetransfer processes with the C 60 triplet acting as the acceptor. (4) (a) Suzuki, T.; Maruyama, Y.; Akasaka, T.; Ando, W.; Kobayashi, K.; Nagase, S. Haddon, R. C.; Knight, B.; Li, Q. C.; Maggini, M.; Martín, N.; Ohno, T.; Prato, M.; Suzuki, T.; Wudl, F. Prato, M.; Carano, M.; Ceroni, P.; Paolucci, F.; Roffia, S.
New Synthetic Inhibitors of Fatty Acid Synthase with Anticancer Activity
Journal of Medicinal Chemistry, 2012
Fatty acid synthase (FASN) is a lipogenic enzyme that is highly expressed in different human cancers. Here we report the development of a new series of polyphenolic compounds 5−30 that have been evaluated for their cytotoxic capacity in SK-Br3 cells, a human breast cancer cell line with high FASN expression. The compounds with an IC 50 < 50 μM have been tested for their ability to inhibit FASN activity. Among them, derivative 30 blocks the 90% of FASN activity at low concentration (4 μM), is highly cytotoxic in a broad panel of tumor cells, induces apoptosis, and blocks the activation of HER2, AKT, and ERK pathways. Remarkably, 30 does not activate carnitine palmitoyltransferase-1 (CPT-1) nor induces in mice weight loss, which are the main drawbacks of other previously described FASN inhibitors. Thus, FASN inhibitor 30 may aid the validation of this enzyme as a therapeutic target for the treatment of cancer.
Study of the conformational profile of the norbornane analogues of phenylalanine
Journal of Peptide Science, 2002
The conformational profile of the eight stereoisomeric 2-amino-3-phenylnorbornane-2-carboxylic acids (2-amino-3-phenylbicyclo[2.2.1]heptane-2-carboxylic acids) has been assessed by computational methods. These molecules constitute a series of four enantiomeric pairs that can be considered as rigid analogues of either L- or D-phenylalanine. The conformational space of their N-acetyl methylamide derivatives has been explored within the molecular mechanics framework, using the parm94 set of parameters of the AMBER force field. Local minimum energy conformations have been further investigated at the ab initio level by means of the Hartree-Fock and second order Moller-Plesset perturbation energy calculations using a 6-31G(d) basis set. The results of the present work suggest that the bulky norbornane structure induces two kinds of conformational constraints on the residues. On one hand, those of a steric nature directly imposed by the bicycle on the peptide backbone and, on the other hand, those that limit the orientations attainable by the phenyl ring which, in turn, reduces further the flexibility of the peptide backbone. A comparative analysis of the conformational profile of the phenylnorbornane amino acids with that of the norbornane amino acids devoid of the beta-phenyl substituent suggests that the norbornane system hampers the residue to adopt extended conformations in favour of C7-like structures. However, the bicycle itself does not impart a clear preference for any of the two possible C7 minima. It is the aromatic side chain, which is forced to adopt an almost eclipsed orientation, that breaks this symmetry introducing a marked preference for a single region of the (phi, psi) conformational space in each of the phenylalanine norbornane analogues investigated.
Chemistry - A European Journal, 2008
The efficient synthesis of large ring size pseudopeptidic macrocycles through a multicomponent [2+2] reductive amination reaction is described. The reaction is completely governed by the structural information contained in the corresponding openchain pseudopeptidic bis(amidoamine) precursors, which bear a rigid (R,R)cyclohexane-1,2-diamine moiety. A remarkable match/mismatch relationship between the configurations of the chiral centers of the cyclic diamine and those of the peptidic frame is observed. The macrocyclic tetraimine intermediates have been deeply studied by NMR, CD and molecular modeling, supporting the appropriate preorganization induced by the match combination of the chiral centers. We have also synthesized the corresponding open-chain bis(imine) model compounds. Structural studies (NMR, CD, modeling) with these systems showed an intrinsic lower reactivity of the mismatch combination, even when the product of the reaction is acyclic. Besides, there is a synergistic effect of both chiral substructures for the correct folding of the molecules. Finally, X-ray analysis of the HCl salt of one of the macrocycles showed an interesting pattern. The macrocyclic rings stack in columnar aggregates leaving large interstitial channels filled with water solvated chloride anions.
Monatshefte Fur Chemie, 2008
In a previous study, we have identified 3-alkyl-1,5-diaryl-1H-1,2,4-triazoles to be a novel class of cannabinoid type-1 (CB1) receptor antagonists. However, the synthesis yields for the ligands were low. Here we present an alternative synthesis pathway with improved yields. In addition, we have synthezised new structural derivatives and studied their results in competitive radioligand binding assays for cannabinoid receptors.
New aminocyclitols as modulators of glucosylceramide metabolism
Organic & Biomolecular Chemistry, 2005
A series of 13 aminocyclitol derivatives belonging to two different families is described. Their configuration is governed by the regio-and stereocontrolled epoxide opening of a suitably protected conduritol-B epoxide. Studies on several glycosyl processing enzymes indicate that some of them are good inhibitors of glucosylceramide hydrolase. A rationale to account for preliminary structure-activity relationships is provided. h e m i s t r y 2 0 0 5 O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 1 9 5 -1 2 0 1 1 1 9 5
Photochemistry and Photobiology, 1998
The decay processes of the lowest excited singlet and triplet states of five methylated angelicins (4,6,4'-trimethylangelicin, MA, and four methylated thioangelicins, MTA; see Scheme 1) were investigated in five solvents by stationary and pulsed fluorometric and flash photolytic techniques. In particular, the solvent effects on absorption, fluorescence, quantum yields of fluorescence (+F) and triplet formation (&), lifetimes of fluorescence ( T~) and the triplet state ( T~) and the quantum yields of singlet oxygen production (+,J were investigated. Semiempirical (ZINDOK-CI) calculations were carried out to obtain information (transition probabilities and nature) on the lowest excited singlet and triplet states. The quantum mechanical calculations and the solvent effect on the photophysical properties showed that the lowest excited singlet state (S,) is a partially allowed n,n* state, while the close-lying S2 state is n,n* in nature. The efficiencies of fluorescence, S, + TI intersystem crossing (ISC) and S1 + So internal conversion (IC) strongly depend on the energy gap between S1 and S2 and are explained in terms of the so-called proximity effect. In fact, for MA in cyclohexane, only the S1 + So internal conversion is operthrough S, -+ So IC only, while in acetonitrile and ethanol, fluorescence and ISC increase significantly. For these compounds there is strong evidence that a '(n,.rr*) state lies just