1192-07-0Relevant articles and documents
Synthesis and in vitro pharmacology of novel heterocyclic muscarinic ligands
De Amici, Marco,Conti, Paola,Fasoli, Ezio,Barocelli, Elisabetta,Ballabeni, Vigilio,Bertoni, Simona,Impicciatore, Mariannina,Roth, Bryan L.,Ernsberger, Paul,De Micheli, Carlo
, p. 739 - 748 (2003)
A set of novel heterocyclic ligands (7a-9a, 7b-9b, and 9c) structurally related to oxotremorine 2 was designed, synthesized, and tested at muscarinic receptor subtypes. In the binding experiments at cloned hm1-5, the presence of the 2-methylimidazole/2-me
3-ISOXAZOLIDONE FROM JACK BEAN SEEDLINGS
Sugii, Michiyasu,Miura, Hiroshi,Nagata, Kazutoshi
, p. 451 - 454 (1981)
Key Word Index - Canavalia ensiformis; Leguminosae; jack bean; 3-isoxazolidone; L-canavanine; L-canaline; pentacyanoammoniferrate reagent; Jaffe reagent. 3-Isoxazolidone has been isolated from jack bean seedlings.
The high selectivity of the Cp2ZrHCl reducing agent for imides: A combined experimental and theoretical study on γ-lactam and isoxazolidinone derivatives
Lanza, Giuseppe,Chiacchio, Maria A.,Giofre, Salvatore V.,Romeo, Roberto,Merino, Pedro
, p. 95 - 104 (2013/02/23)
Selective reductions of semicyclic imides either to hemiaminals (endo carbonyl reduction) or to aldehydes and amines (exo carbonyl reduction) in high yields by Schwartz's reagent (Cp2ZrHCl) are reported. Mechanistic aspects of these reactions have been investigated at the DFT ab initio level with consideration of implicit solvent effects and thermal and pressure corrections to 298 K/1 atm. The reactions proceed from the reagents to very stable final Zr-oxo intermediates through the formation of σ complexes and subsequent four-center transition state structures (1,2-migratory insertion). The energetic barriers for the insertion steps depend strongly on the natures of the ancillary groups at the reducing carbonyl groups. N-Carbamoyl groups are reduced to hemiaminals whereas N-acyl groups react at the exo carbonyl groups. The absence of the second carbonyl group in the simple N-methyl-2-pyrrolidone (less oxidized system) strongly reduces the thermodynamic drive for the formation of the metallocene oxo intermediate and allows an explanation of the remarkable chemoselectivity of the hydrozirconation. The zirconocene-oxo intermediates hydrolyze quickly throughout an ionic mechanism in which water molecules strongly assist the process by stabilizing ion pair separation. The computational results are consistent with a large set of experimental data on reduction of γ-lactam and isoxazolidinone derivatives under mild conditions. They provide a way to explain and predict the relative importance of the two competitive endo/exo reduction channels of semicyclic imides by considering the electronic and steric features of substituents. Semicyclic imides such as γ-lactam and isoxazolidinone derivatives are efficiently and selectivity reduced by the Cp2ZrHCl agent. The energetic reaction pathways for endo and exo attack, computed at the DFT level including thermal effects, allow an exhaustive interpretation of current and previously reported experimental data. Copyright
3-Aminoxypropionate-based linker system for cyclization activation in prodrug design
Ge, Yiyu,Wu, Xinghua,Zhang, Dazhi,Hu, Longqin
scheme or table, p. 941 - 944 (2009/08/15)
A novel linker system based on 3-aminoxypropionate was designed and evaluated for drug release using proteolysis as an activation trigger followed by intramolecular cyclization. The hydroxylamine moiety present in the linker system enabled faster release of the parent drug from the linker-drug conjugate at lower pH as compared to an aliphatic amine moiety. Introduction of two methyl groups strategically at the α position to the carboxylate in the linker further improved the rate of cyclization by nearly 2-fold. The 3-aminoxypropionate linker was successfully applied to a model prodrug for protease activation using α-chymotrypsin as the activating enzyme; the activation of the model prodrug bearing the 3-aminoxypropionate linker was 136 times faster than the corresponding model prodrug bearing an amine linker.
Enantioselective enolate protonations: Friedel-crafts reactions with α-substituted acrylates
Sibi, Mukund P.,Coulomb, Julien,Stanley, Levi M.
supporting information; experimental part, p. 9913 - 9915 (2009/05/07)
(Chemical Equation Presented) Templates rule: A Zn(NTf2) 2/1 catalyzed tandem Friedel-Crafts alkylation/enantioselective protonation of pyrroles with isoxazolidinone-derived α-substituted a,b-unsaturated imides, provides high levels
Cyclic hydroxamates, especially multiply substituted [1,2]oxazinan-3-ones
Wolfe, Saul,Wilson, Marie-Claire,Cheng, Ming-Huei,Shustov, Gennady V.,Akuche, Christiana I.
, p. 937 - 960 (2007/10/03)
Routes to putative N-acyl-D-ala-D-ala surrogates, beginning with the conversion of 4-, 5-, and 6-membered lactones into 5-, 6-, and 7-membered cyclic hydroxamates, are reported. The key step of the synthesis is trimethylaluminium-promoted cyclization of an ω-aminooxyester. The 7-membered cyclic hydroxamate crystallizes in a chair conformation. Extension of the reaction sequence to homoserine or homoserine lactone leads to cyclocanaline and N-acylated cyclocanalines. The 4-phenylacetamido derivative of cyclocanaline crystallizes in a boat conformation. The attachment of a 2-carboxypropyl substituent to the ring nitrogen of a 4-acylaminocyclocanaline has been effected, prior to cyclization, by coupling of the acyclic aminooxyester precursor to the triflate of benzyl lactate or, after cyclization, by coupling to tert-butyl α-bromopropionate in the presence of potassium fluoride - alumina, followed by removal of the protecting group in each case. A six-membered homolog of the antibiotic lactivicin has been synthesized by the reaction of 4-phenylacetamidocyclocanaline with benzyl 2-oxoglutarate in the presence of carbodiimide, followed by hydrogenolysis. Starting with methyl 2,4-dibromo-2,4-dideoxy-L-erythronate, which is available in two steps from L-ascorbic acid, these reaction sequences have been applied to the stereospecific synthesis of a D-alanine derivative whose nitrogen atom is enclosed within a 3,4-disubstituted [1,2]oxazinan-3-one.
Synthesis and functional characterization of novel derivatives related to oxotremorine and oxotremorine-M
Dallanoce, Clelia,Conti, Paola,De Amici, Marco,De Micheli, Carlo,Barocelli, Elisabetta,Chiavarini, Milena,Ballabeni, Vigilio,Bertoni, Simona,Impicciatore, Mariannina
, p. 1539 - 1547 (2007/10/03)
Two subseries of nonquaternized (5a-10a) and quaternized derivatives (5b-10b) related to oxotremorine and oxotremorine-M were synthesized and tested. The agonist potency at the muscarinic receptor subtypes of the new compounds was estimated in three class
Absence of Stereoelectronic Control in Hydrolysis of Cyclic Amidines
Perrin, Charles L.,Nunez, Oswaldo
, p. 5997 - 6003 (2007/10/02)
According to Deslongchamps' theory of stereoelectronic control, preferentioal cleavage of a tetrahedral intermediate occurs when there are two lone pairs antiperiplanar to the leaving group.For reasons presented (Perrin and Arrhenius, J.Am.Chem.Soc. 1982, 104, 2839), product studies of hydrolysis of cyclic amidines can test this theory, and initial results supported it.However, those results are ambiguous, owing to a mismatch of leaving abilities.We now find that hydrolysis of three six-membered ring amidines bearing matched leaving groups produces predominantly aminoamide, the product of ring cleavage, and only 3-9percent lactam, as expected from the theory.In contrast, hydrolysis of three five- or seven-membered ring amidines produces substantial (ca. 50percent) lactam.Despite attempts to accomodate these results to the theory, it is concluded that there is no general requirement for two lone pairs antiperiplanar to the leaving group and that stereoelectronic control, even in six-membered ring amidines, contributes less than 2 kcal/mol.
