53399-81-8Relevant articles and documents
Structure-activity studies of fluoroalkyl-substituted γ-butyrolactone and γ-thiobutyrolactone modulators of GABA(A) receptor function
Canney, Daniel J.,Lu, Hwang-Fun,McKeon, Ann C.,Yoon, Kong-Woo,Xu, Kun,Holland, Katherine D.,Rothman, Steven M.,Ferrendelli, James A.,Covey, Douglas F.
, p. 43 - 55 (1998)
Dihydro-2(3H)-furanones (γ-butyrolactones) and dihydro-2(3H)-thiophenones (γ-thiobutyrolactones) containing fluoroalkyl groups at positions C-3, C-4, and C-5 of the heterocyclic rings were prepared. The anticonvulsant/convulsant activities of the compounds were evaluated in mice. Brain concentrations of the compounds were determined and the effects of the compounds on [35S]-tert-butylbicyclophosphorothionate ([35S]TBPS) binding to the picrotoxin site on GABA(A) receptors were investigated. The effects of the compounds on GABA(A) receptor function were studied using electrophysiological methods and cultured rat hippocampal neurons. Fluorination at C-3 results in either subtle or pronounced effects on the pharmacological activity of the compounds. When hydrogens are replaced with fluorines at the methylene carbon of an ethyl group, as in 3-(1,1-difluoroethyl)dihydro-3-methyl-2(3H)-furanone (1), the anticonvulsant actions of the compound are not much changed from those found for the corresponding alkyl-substituted analogue. In marked contrast, fluorination at the methyl carbon of the ethyl group, as in dihydro-3-methyl-3-(2,2,2-trifluoroethyl)-2(3H)-furanone (3), produces a compound having convulsant activity. This convulsant activity seems to be due to an increased affinity of the compound for the picrotoxin site on GABA(A) receptors caused by an interaction that involves the trifluoromethyl group. Results obtained with γ-butyrolactones containing either a 3-(1-trifluoromethyl)ethyl or a 3-(1-methyl-1-trifluoromethyl)ethyl substitutent indicate that the interactions of the trifluoromethyl group with the picrotoxin binding site are subject to both stereochemical and steric constraints. Sulfur for oxygen heteroatom substitution, as in the corresponding γ-thiobutyrolactones, affects the type (competitive, noncompetitive, etc.) of binding interactions that these compounds have with the picrotoxin site in a complex manner. Fluorination of alkyl groups at the C-4 and C-5 positions of γ-butyrolactones having convulsant activity increases convulsant potency.
An improved solvent-free system for the microwave-assisted decarboxylation of malonate derivatives based on the use of imidazole
Tellitu, Imanol,Beitia, Itziar,Díaz, Marta,Alonso, Argi?e,Moreno, Isabel,Domínguez, Esther
, p. 8251 - 8255 (2015/10/05)
A comparative study of the thermal and microwave-assisted decarboxylation of a series of mono- and disubstituted monohydrolyzed malonate derivatives has been carried out. It has been found out that in both circumstances the use of imidazole has a profound effect on the success of the reaction. In general terms the assistance of microwave irradiation accelerates the decarboxylation process significantly and, at the same time, permits the use of minored temperatures with respect to the thermal via. It has been also found that both the thermal and the microwave-assisted transformation can be developed under solvent-free conditions.
Remote control of regio- and diastereoselectivity in the hydroformylation of bishomoallylic alcohols with catalytic amounts of a reversibly bound directing group
Gruenanger, Christian U.,Breit, Bernhard
supporting information; experimental part, p. 967 - 970 (2010/05/02)
(Figure Presented) Remote and reversible! Phosphinites serve as reversibly bound directing groups for the remote control of the regio- and diastereoselective hydroformylation of bishomoallylic alcohols (see scheme; r.r: regioisomer ratio). The distance between the double bond and the functional hydroxy group to which the directing group is reversibly bound is the longest ever reported.
Construction of vicinal quaternary carbon atoms by Ireland ester Claisen rearrangement: Total synthesis of (±)-herbertenolide, (±)-herberteneacetal, (±)-herbertene-1,14-diol and (±)-herbertene-1,15-diol
Srikrishna,Vasantha Lakshmi
, p. 4879 - 4881 (2007/10/03)
Efficient total syntheses of the herbertane sesquiterpene title compounds have been accomplished employing an Ireland ester Claisen rearrangement and ring-closing metathesis reaction sequence based strategy for the construction of two stereogenic vicinal quaternary carbon atoms on a cyclopentane.
Steric effects in intramolecular [2+2] photocycloaddition of C=C double bonds to cyclohexenones
Becker,Haddad
, p. 947 - 964 (2007/10/02)
The effect of substituents on the mode of approach and the endo/exo ratio in intramolecular [2+2] photocycloaddition reactions were studied.
HALOCYCLIZATIONS: THE CYCLIZATION OF HETEROCYCLIC OLEFINIC AMIDES AND UREAS
Balko, T. W.,Brinkmeyer, R. S.,Terando, N. H.
, p. 2045 - 2048 (2007/10/02)
The halocyclization of N-heterocyclicpentenamides and allylureas with N-bromosuccinimide yields the pyrrolidinones 3 and imidazolidinones 5, respectively.The thiazolylpentenamide also yields the 6-membered ring lactam.
Dimerization of Pyrazolyl-5-hydroxypyrrolidinones to Tetrazocines
Brinkmeyer, Raymond S.,Terando, Norman H.
, p. 1713 - 1717 (2007/10/02)
The dimerization of the hydroxypyrrolidinones 5 and 9 yield the tetrazocines 8 and 11.In addition, in the case of compound 9, the ring-fused hexaazacyclododecane 12 was isolated.X-ray diffraction analysis of compound 11 verified the dimeric structure of these products.
A New Route to the Prostaglandin Skeleton via Radical Alkylation. Synthesis of 6-Oxoprostaglandin E1
Toru, Takeshi,Yamada, Yoshio,Ueno, Toshio,Maekawa, Eturo,Ueno, Yoshio
, p. 4815 - 4817 (2007/10/02)
A new, mild, and efficient method for the construction of the prostanoid skeleton involving cuprate addition to α-(phenylseleno)cyclopentenones followed by radical-based coupling to the resulting products with allylstannane derivatives is described.The method is applied to the synthesis of 6-oxoprostaglandin E1, a biologically active and naturally occurring compound.
Synthetic Studies Relevant to Biosynthetic Research on Vitamin B12. Part 5. Synthesis of (RS)-Ring-B Imide
Battersby, Alan R.,Westwood, Steven W.
, p. 1679 - 1688 (2007/10/02)
Future biosynthetic research on vitamin B12 depends on the synthesis of a family of isobacteriochlorin pigments.A key building block required for this work is 2-(2-methoxycarbonylethyl)-3-methoxycarbonylmethyl-3-methylsuccinimide, usually called the ring-B imide.A practical synthesis of the racemic form of this substance is described which can yield multigramme quantities of product.
DICOBALTOCTACARBONYL-ALKYNE COMPLEXES AS INTERMEDIATES IN THE SYNTHESIS OF BICYCLOOCTENONES FOR THE SYNTHESIS OF CORIOLIN AND HIRSUTIC ACID
Magnus, Philip,Exon, Christopher,Albaugh-Robertson, Pamela
, p. 5861 - 5869 (2007/10/02)
Treatment of the readily prepared enzynes 12, 21 and 45 with Co2(CO)8 at ca 110 deg C results in high yields (80percent) of substituted bicyclooctenones, that are suitable for straightforward elaboration into coriolin and hirsutic acid precursors.A mechanistic hypothesis to explain the observed stereospecificity is presented.
