Ma Teresa García-López

Stereoselective reductive amination of β-keto esters derived from dipeptides. Stereochemical and mechanistic studies on the formation of 5-carboxymethyl-2-oxopiperazine derivatives

Abstract The stereoselective generation of 3,5-disubstituted and 3,5,6-trisubstituted 2-oxopiperazine derivatives can be accomplished by intramolecular reductive amination of β-keto esters derived from Z-Xaa-Gly-OH and Z-Xaa-Yaa- OH dipeptides, respectively. Differences in the stereoselectivity between the use of NaBH 3 CN and hydrogen as reducing agents are due to the reduction of different intermediates, as deduced from experiments of isotopic labelling with deuterium.

3,6-dioxoperhydropyrrolo[1,2-a]pyrazines. A new approach to conformationally restricted tripeptides

Abstract Catalytic hydrogenation of the 4-ketodiesters, obtained fom Z-Xaa-Gly (Xaa= Ala, Phe) halomethyl ketones and dimethyl malonate, provides readily access to the corresponding 4-substituted-3,6-dioxoperhydropyrrolo[1,2-a]pyrazine-7-carboxylic acid derivatives with high degree of stereocontrol at the new chiral centers. Alkylation of these bicyclic bis-lactams with benzyl bromide gave the corresponding Xaa-Gly-Phe restricted tripeptides.

Exploring solid-phase approaches for the preparation of new β-lactams from amino acids

Two solid-phase approaches, involving the base-assisted intramolecularalkylation of N-chloroacetyl-Phe derivatives anchored to appropriatesolid supports, were investigated for the preparation of novel β-lactams. When a BAL-type strategy was used, the resin-bound azetidinones were easily formed, as established by MAS-NMR, but final compounds could not be removed from the resin, unless a suitable two linkers system was used. In the second approach, in which the Phe residue is anchored to a Wang-type resin through the carboxylate group, the corresponding 1,4,4-trisubstituted 2-azetidinone was obtained in moderate to good yield and high purity.

Synthesis of 2-(β-D-Ribofuranosyl)Thiazole-4-Carboxamide 5′-Phosphate Isosteres

Abstract SUMMARY. The syntheses of 5′-O-sulfamoyl and 5′-O-carbamoyl tiazofurin (9 and 12) are described. One pot reaction of 2′, 3′-O-isopropylidene-tiazofurin (7) with hexabutyldistannoxane and sulfamoyl chloride gave the corresponding 5′-O-sulfamoyl ester, which was deprotected to yield 9. Compound 7 reacted with phenyl chloroformate to give the 5′-O-carbophenoxy derivative which on treatment with ammonium hydroxide followed by deisopropylidenation afforded 12. Improvements on the synthetic route to the starting tiazofurin are also reported.

Uridine-5′-Diphosphate Glucose Analogues. 21. Nucleoside Modified Analogues of Antiviral 5′-O-[[[[(α-D-Glucopyranosyl)Oxy Carbonyl]Amino]Sulfonyl]Uridine Derivatives

Abstract A series of uridine modified analogues of antiviral 5′-O-[[[[(α-D-glucopyranosyl) oxy] carbonyl]amno]sulfonyl]uridine derivatives has been synthesized by reaction of suitably protected glucose and glucosamine derivatives with CISO2-N=C=O and thymidine, 2′-deoxyuridine, 3-methyluridine, 5, 6-dihydrouridine and 1-[(2-hydroxyethoxy) methyl] uracil derivatives. The antiviral activity against HSV-1 has been determined.

Amino Acid-derived 4-Alkyl-4-carboxy-2-azetidinones. New Insights into b-Lactam Ring Formation and N-Deprotection

The preparation and N-deprotection of a series of phenylalanine-derived 2-azetidinones incorporating 2,4-dimethoxybenzyl (Dmb), 2,3,4-, 2,4,6- and 3,4,5-trimethoxybenzyl (Tmb) groups at 1 position are described. The base-promoted cyclization of the corresponding methoxy-substituted N α -benzyl-N α -chloroacetyl derivatives to the 1,4,4-trisubstituted azetidinones proceeded with moderate to good yields, except for the 2,4,6-Tmb analogue. In spite of the number and position of the OMe groups, N-unsubstituted β-lactams were obtained by oxidative debenzylation using potassium peroxodisulfate. Alternatively, debenzylation of Pmb, Dmb and Tmb 2-azetidinones with TFA/anisole resulted in concomitant β-lactam opening to α-benzylaspartic acid derivatives.

Synthesis of highly functionalized γ-lactam derivatives for use as conformational constraints in peptides

Abstract A series of highly functionalized 2-oxopyrrolidine derivatives, as tripeptidemimetics in which the amino acid side chains are mounted on the γ-lactam template, were synthesized by nucleophilic opening of the δ-lactam system of the corresponding 3,6-dioxopyrrolo[1,2- a ]pyrazine bicyclic analogues.

Synthesis of methyl 6-aralkl-2,5-diketopiperidine-3-carboxylates as synthons of conformationally constrained pseudopeptides

Abstract Catalytic hydrogenation of the 4-ketoesters 1a,b or 2a,b and their 5R-enantiomers, obtained from the corresponding Z-L- and Z-D-amino acid halomethyl ketones, directly leads to the methyl 6-aralkyl-2,5-diketopiperidine-3-carboxylates 3a,b and 4a,b and their 6R-enantiomers with high or moderate stereoselectivity at C-3.

5′-O-[N-(Amnoacyl)Sulfamoyl]Nucleosides. Synthesis and Antiviral and Cytostatic Activities

Abstract 5′-O-[N-(Aminoacyl)sulfamoyl]-uridines and -thymidines 4a-12a and 4b-12b have been synthesized and tested against Herpes Simplex virus type 2 (HSV-2) and as cytostatics. Condensation of 2′,3′-O-isopropylidene-5′-O-sulfamoyluridine and 3′-O-acetyl-5′-O-sulfamoylthymidine with the N-hydroxysuccinimide esters of Boc-L-Ser(Bzl), (2R, 3S)-3-benzyloxycarbonylamino-2-hydroxy-4-phenylbuta-noic acid [(2R, 3S-N-Z-AHPBA], (2R, 3S) and (2S, 3R)-N-Boc-AHPBA gave 4a,b-7a,b, which after removal of the protecting groups provided 1Oa,b-12a,b. A study of the selective removal of the O-Bzl protecting group from the L-Ser derivatives 4a,b, without hydrogenation of the pyrimidine ring, has been carried out. Only the fully protected uridine derivatives 4a-7a did exhibit high anti-HSV-2 activity, and none of the synthesized compounds showed significant cytostatic activity against HeLa cells cultures.

Solid-phase synthesis of new Trp(Nps)-containing dipeptide derivatives as TRPV1 channel blockers.

Trp(Nps)-Lys-NH2 derivatives, bearing alkyl or guanidine groups either at the N–terminus or on the Lys side-chain or at both positions were conveniently prepared on solid-phase and evaluated as TRPV1 channel antagonists.