Concepción Pedregal

Highly chemoselective reduction of N-Boc protected lactams

Abstract N-Boc protected lactams can be reduced chemoselectively in the presence of other groups such as esters, nitriles, carbamates or double bonds by first reducing the amide carbonyl group into the corresponding hemiaminal using lithium triethylborohydride followed by further reduction of the hemiaminal intermediate with triethylsilane/Boron trifluoride etherate. This method preserves the chirality present in the substrate.

Stereoselective reactions of lithium enolates derived from N-BOC protected pyroglutamic esters

Abstract The lithium enolates of N-Boc protected pyroglutamic ethyl or tert -butyl esters react with electrophiles in good yield without epimerization of the chiral centre. With benzyl bromides the process is stereospecific, yielding exclusively the trans isomer. However, with other reactive electrophiles a 2:1 trans/cis diastereomeric mixture was obtained, regardless of the steric bulk of the ester group.

Regioselective ring opening of chiral N-Boc protected pyroglutamate and pyroaminoadipate ethyl esters with heteronucleophiles

Abstract Mixed diesters, ω-amide and ω-thioesters are obtained from both N-Boc ethyl pyroglutamate and pyroaminoadipate under neutral or basic conditions. Under neutral conditions, the reaction is catalyzed by KCN and the use of Ultrasound speeds up the process. In basic conditions, reaction times are even shorter. In both cases, no transesterification of the α-ester was observed and the chirality of the α-amino acid was preserved.

Regioselective nucleophilic attack on N-BOC-pyroglutamate ethyl ester

Abstract N-BOC ethyl pyroglutamate undergoes regioselective ring opening with different nucleophiles without racemization at the chiral centre.

Diastereoselective functionalization of 5-hydroxy prolinates by tandem Horner-Emmons-Michael reaction

Abstract The tandem Horner-Emmons-Michael reaction of the hemiaminal derived from N -BOC protected pyroglutamic esters with stabilised phosphonates gives 5-substituted prolinates in high diastereometric and enantiomeric excess through a 1,4-asymmetric induction process.

Ethyl N-(diphenylmethylene)glycinate as anionic glycine equivalent. Monoalkylation, dialkylation and Michael additions under solid-liquid phase-transfer catalysis

Abstract Ethyl N -(diphenylmethylene)glycinate, 1 , undergoes monoalkylations, dialkylations and Michael additions to ethylenic and acetylenic acceptors under appropriate solid-liquid phase transfer catalysis conditions. Further transformations of the α-disubstituted ketimines lead to α-alkylated aspartic and glutamic acid derivatives 10 , 15 , 19 and 26 , to bicyclic amino acids or derivatives featuring pyrazolone and isoxazolone moieties 30 and 33 , and to α-substituted ( E )-3,4-dehydroglutamic acids.

Short and efficient enantioselective synthesis of cis and trans pyrrolidine-2,5 dicarboxylic acids

Abstract N-BOC-ethyl pyroglutamate 1 undergoes nucleophilic ring opening with lithium methyl p-tolyl sulfinyl anion delivering the p-tolylketosulfoxide 2. Treatment of 2 with TFA gave rise to a mixture of thioesters 3a,3b. The hydrolysis of 3b afforded (2S, 5S) pirrolidine-2,5 dicarboxylic acid 5, a constituent of the red Alga Schizymenia dubyi . Under Pummerer reaction conditions (TFAA/Pyr), 2 yielded the 5-oxo-L-pipecolic acid derivative 6.

General method for the synthesis of 5-arylpyrrole-2-carboxylic acids

This research was conducted under the Spanish FARMA II programme (Ministerio de lndustria). J. V. is grateful to Lilly,S. A. for a fellowship.

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.