Carmen Dominguez

Enantiospecific synthesis of (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid by a modified Corey-Link reaction

Abstract ( 1S,2S,5R,6S )-2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740) was synthesised enantiospecifically from a sugar derived enantiomerically pure cyclopentenone. The α-amino acid stereogenic centre was formed by reacting the ketone with chloroform anion and then the alcohol so formed was reacted with sodium azide/DBU in methanol to give an azido ester. Critically, this modified Corey-Link reaction gives the opposite stereochemical outcome to the traditional Bucherer-Bergs and Strecker reactions. The azide was reduced and acylated, the 1,2 diol deoxygenated and the protecting groups removed to give LY354740 with an e.e.>98%.

MAGNESIUM MONOPEROXYPHTALATE : A NEW REAGENT FOR THE OXIDATIVE RING OPENING OF FURANS TO CIS-ENEDIONES

Abstract Ring opening of furans can be accomplished with the title reagent to afford cis -enediones stereospecifically, with great advantages over the hazardous MCPBA.

Asymmetric synthesis of (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740)

Abstract The asymmetric synthesis of (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740) 1, a potent and selective group 2 mGluR agonist, has been accomplished starting from the readily available enantiomerically pure cyclopentenone 4. Thus, cyclopropanation with ethyl(dimethylsulfuranylidene)acetate generated in situ with DBU, followed by deketalization gave rise to the dihydroxy bicyclic ketone 9. After protecting the ketone as 1,3-dioxolane and its transformation to the orthoformate 11, this was pyrolytically deoxygenated in a sealed tube to the bicyclic enone 13. The synthesis was completed after hydrogenation, stereoselective Bucherer-Bergs reaction and hydantoin hydrolysis, yielding LY354740 (+)-1 with an e.e. ≥98%.

4-Alkylidenyl glutamic acids, potent and selective GluR5 agonists

Twenty-four 4-alkylidene glutamic acids were synthesised and tested as potential subtype selective GluR5 and 6 ligands. It was found that a critical size of alkylidene group gave potent and selective GluR5 receptor agonists. LY339624 had Kis of 0.0326 and >100 microM on GluR5 and 6 receptors, respectively.

Stereoselective cyclopropanation of enones with ethyl dimethylsulfonium acetate bromide in the presence of DBU

Abstract The cyclopropanation reaction of α, β-unsaturated ketones 1a-c with ethyl (dimethyl sulfuranylidene) acetate (EDSA), generated in situ from the corresponding sulfonium bromide salt and 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) in toluene, leads exclusively to the exo adduct 2a-c (d.e.=100%). Acyclic enones 1d-g , give mainly the “trans” cyclopropanes 4d-g with a high degree of stereocontrol (d.e. 3 80%). Changing the solvent to CHCl 3 affords a 2:1 mixture of “trans” and “cis” cyclopropanes 4d-g and 5d-g respectively. The “cis” isomers 5d-g can be epimerizated to the alternative “trans” isomers 6d-g under basic conditions.

Chemoselective reduction in carbonyl-conjugated vinylfurans by the Mg/MeOH system

Abstract Chemoselective reduction of double bonds conjugated with carbonyl groups and furan rings has been accomplished by using Mg/MeOH reducing system.

New aspects in the regioselective functionalization of furans. Synthesis of Tri- and tetrasubstituted furan derivatives

Abstract Application of directed ortho metalation reaction and electrophilic aromatic substitution allows for the regioselective synthesis of tri- and tetrasubstituted furans, thus superseding classical de novo furan construction modes.

Abatement of chlorinated compounds in groundwater contaminated by HCH wastes using ISCO with alkali activated persulfate

In this work, in situ chemical oxidation (ISCO) with alkali activated persulfate has been tested for the elimination of HCH isomers and other chlorinated compounds in groundwater from Sabiñanigo (Sardas landfill), which was contaminated by solid and liquid wastes illegally dumped in the area by a company producing lindane. Due to the site lithology and the type of pollutants found in groundwater (HCHs and chlorobenzenes) alkali (NaOH) activated persulfate (PS) was selected as oxidant. The influence of variables such as PS concentration (42-200mM) and NaOH:PS molar ratio (2:1 to 4:1) on chlorinated compound abatement has been studied and a kinetic model to predict the composition of all chlorinated organic compounds (COCs) in the aqueous phase with time was obtained. It was found that a fast initial hydrodechlorination reaction took place in which HCH isomers reacted to trichlorobenzenes (mainly 1,2,4 TCB) at pH≥12. Mono-, di-, tri and tetrachlorobenzenes remaining were oxidized without producing aromatic intermediates. At the condition tested a first order kinetic model for COCs and PS concentration was obtained. Zero order alkali concentration was obtained while pH was being kept at 12 for the whole reaction time.

1,3-Dipolar cycloadditions of benzonitrile oxide to vinyl and azavinyl furan derivatives

Abstract The regiospecific and site-selective 1,3-dipolar cycloaddition reactions of benzonitrile oxide (BNO) to the CC and the CN double bonds of some furyl-substituted dipolarophiles is reported.

The Eastman's reaction revisited

Several previously unknown 3-acyl-5-alkyl-1-arylpyrazoles, differently functionalized in the 3- and 5- side chains, have been synthesized from appropriate 2,5-disubstituted furans by their reaction with p-nitrobenzenediazonium salts.