Papers by Jose M. Villalgordo
X-ray structure of a pentameric ligand gated ion channel from Erwinia chrysanthemi (ELIC) in complex with memantine
Crystal structure of a mutant binding protein (5HTBP-AChBP) in complex with serotonin (5-hydroxytryptamine)
ChemInform Abstract: exo,exo-2-Amino-3-borneol-Derived Oxazolidinone as a New Chiral Auxiliary for Use in Asymmetric Transformations
ChemInform, 2010
Synthesis of Novel 2,3-Dihydroimidazo[2,1- b ][1,3]oxazoles Through Intramolecular Nucleophilic ipso -Substitution in 2-Alkylsulfonylimidazoles
Synthesis, 2002
ABSTRACT
ChemInform, 2010
In this account dedicated to' 100 years Roche' in CHIMIA, we present some of our strategies towar... more In this account dedicated to' 100 years Roche' in CHIMIA, we present some of our strategies towards the synthesis of interesting novel amino-acid-derived building blocks; multi generation synthesis of thiazole libraries in solution; a novel solid-phase approach towards highly substituted pyrimidines using a novel safety-catch linker principle and a multidirectional cleavage procedure; a versatile solid-phase synthesis of quinazolones taking advantage of the Staudinger phosphorylimine chemistry combined with a novel cyclization and cleavage strategy, and finally a novel solid-phase diketopiperazine synthesis combining the Ugi four-component reaction with a final ring-forming cleavage step.
ChemInform Abstract: A Highly Efficient and Straightforward Stereoselective Synthesis of Novel Chiral α-Acetylenic Ketones
ChemInform, 2010
ABSTRACT
Tetrahedron: Asymmetry, 2000
A simple and ecient methodology toward the stereoselective synthesis of novel, enantiomerically p... more A simple and ecient methodology toward the stereoselective synthesis of novel, enantiomerically pure, pyrazolyl-b-amino alcohols is presented. Thus, when hydrazines 4a,b were allowed to react at 0 C with chiral a-acetylenic ketones of type 3, pyrazolyl oxazolidine derivatives 5a±d were formed with total regioselectivity in 92±97% yield. Subsequent oxazolidine ring opening by means of TFA, and re-protection of the amino group as the N-Boc derivatives, aorded enantiopure amino alcohols 7a±d.
Tetrahedron, 2006
Fused pyrimidine derivatives R 0515 A Simple Approach for the Regioselective Synthesis of Imidazo... more Fused pyrimidine derivatives R 0515 A Simple Approach for the Regioselective Synthesis of Imidazo[1,2-a]pyrimidinones and Pyrimido[1,2-a]pyrimidinones.-The title compounds are of biological interest.-(FONT, D.;
Tetrahedron, 2001
reaction between a-iminomethylene amino esters with different mono-and bidentate nucleophiles has... more reaction between a-iminomethylene amino esters with different mono-and bidentate nucleophiles has been studied. It has been shown that the reactions with primary and secondary amines as monodentate nucleophiles afford 2-aminoimidazolones ef®ciently under very mild conditions. Judicious selection of the primary amines employed can modulate the regioselectivity. Analogous reactions employing bidentate nucleophiles (e.g. amidines) also afford imidazolyl derivatives. The formation of the latter is preferred over the formation of sevenmembered heterocycles of the triazepinone type. The optimized methodology in solution described herein should be readily adaptable to use in the solid phase for the parallel synthesis of collections of 2-aminoimidazolone derivatives with a high degree of molecular diversity.
A New Class of Fused Imidazoles by Intramolecular Nucleophilic ipso-Substitution in 2-Alkylsulfonylimidazoles: Synthesis of 2,3-Dihydroimidazo[2,1-b][1,3]oxazoles
Synthesis, 1999
ABSTRACT
Synthesis, 2001
Starting from readily available a-diazo-b-keto esters 8 and aromatic primary thioamides 9 and 14,... more Starting from readily available a-diazo-b-keto esters 8 and aromatic primary thioamides 9 and 14, a simple synthesis of 2aryl 4-substituted thiazole-5-carboxylate derivatives of type 10 and 16 has been accomplished. The method is based on the efficient catalysis of CuBr, which promotes the formation of the corresponding carbenoids 11 from diazo derivatives 8. These Cu-carbenoids 11 react with the thiocarbonyl group of the primary thioamides to afford presumably intermediates of the general type 12, which by subsequent cyclocondensation furnish the title thiazole derivatives.
Fused Thiazoles from 3-Amino-2-thioxo-2,3-dihydrothiazoles: Synthesis of Mesoionic Thiazolo[2,3- b ]-1,3,4-thiadiazoles and 2,3-Dihydro-4 H -thiazolo[2,3- b ][1,3,4]thiadiazin-5-ium Derivatives
Synthesis, 1988
Synthese des composes du titre par reaction d'isocyanates aryliques avec des bromures d'a... more Synthese des composes du titre par reaction d'isocyanates aryliques avec des bromures d'amino-3 benzylthio-2 phenyl-4 thiazolium-3, ou par reaction de bromo-2 acetophenones avec des arylidenamino-3 phenyl-4 thiazoline-4thiones-2
Synthesis, 2002
Pyrimidine derivatives Pyrimidine derivatives R 0510 Development of an Efficient and Straightforw... more Pyrimidine derivatives Pyrimidine derivatives R 0510 Development of an Efficient and Straightforward Methodology Toward the Synthesis of Molecularly Diverse 2,6-Disubstituted 3,4-Dihydropyrimidin-4(3H)-ones.-The synthesis of diversely 2,6-disubstituted 3,4-dihydropyrimidin-4(3H)-ones is based on the selective O-alkylation of the pyrimidinones (III) with alcohols under Mitsunobu conditions followed by oxidation to the sulfones (VI) and a variety of nucleophilic heteroaromatic ipso-substitution reactions.-(FONT, D.;
Solid-Phase Synthesis of 3H-Quinazolin-4-ones Based on an Aza Wittig-Mediated annulation Strategy
Synlett, 1998
Aza Wittig-mediated annulation provides a highly efficient and straightforward strategy for the p... more Aza Wittig-mediated annulation provides a highly efficient and straightforward strategy for the parallel synthesis of 3H-quinazolin-4-ones on solid support. The products were recovered in good yields and exhibited excellent purities.
Helvetica Chimica Acta, 1997
Dedicated to Professor Dr. Huns-Jiirgen Hunsen on the occasion of his 60th birthday (6.1.97) The ... more Dedicated to Professor Dr. Huns-Jiirgen Hunsen on the occasion of his 60th birthday (6.1.97) The 2,2-disubstituted 2H-azirin-3-amines 7 (2,2-disubstituted 3-amino-2H-azirines) were used as amino-acid synthons in the preparation of medium-sized cyclic depsipeptides and peptides derived from salicylic acids 6 and anthranilic acid 19, respectively (Schemes 2-4 and 5, resp.). The combination of the 'azirine/oxazolone method' for the synthesis of linear peptides containing a,a-disubstituted a-amino acids and the acid-catalyzed amide cyclization in DMF at 60" proved to be an excellent preparative route to ten-membered cyclic depsipeptides and peptides. In the case of the anthranilic-acid derivative, a transannular ring-closure reaction was observed (24 + 25). Larger rings proved to be extremely sensitive to hydrolysis.
Reactions of 2-Monosubstituted 3-Amino-2H-azirines with NH-Acidic Heterocycles
Helvetica Chimica Acta, 1992
ABSTRACT
Reaction of 3-Amino-2H-azirines with 2-Amino-4,6-dinitrophenol (Picramic Acid): Synthesis of Quinazoline- and 1,3-Benzoxazole Derivatives
Helvetica Chimica Acta, 1990
ABSTRACT The reaction of 3-(dimethylamino)-2H-azirines 1a–c and 2-amino-4,6-dinitrophenol (picram... more ABSTRACT The reaction of 3-(dimethylamino)-2H-azirines 1a–c and 2-amino-4,6-dinitrophenol (picramic acid, 2) in MeCN at 0° to room temperature leads to a mixture of the corresponding 1,2,3,4-tetrahydroquinazoline-2-one 5, 3-(dimethylamino)-1,2-dihydroquinazoline 6, 2-(1-aminoalkyl)-1,3-benzoxazole 7, and N-[2-(dimethylamino)phenyl]-α-aminocarboxamide 8 (Scheme 3). Under the same conditions, 3-(N-methyl-N-phenyl-amino)-2H-azirines 1d and 1e react with 2 to give exclusively the 1,3-benzoxazole derivative 7. The structure of the products has been established by X-ray crystallography. Two different reaction mechanisms for the formation of 7 are discussed in Scheme 6. Treatment of 7 with phenyl isocyanate, 4-nitrobenzoyl chloride, tosyl chloride, and HCl leads to a derivatization of the NH2-group of 7 (Scheme 4). With NaOH or NaOMe as well as with morpholine, 7 is transformed into quinazoline derivatives 5, 14, and 15, respectively, via ring expansion (Scheme 5). In case of the reaction with morpholine, a second product 16, corresponding to structure 8, is isolated. With these results, the reaction of 1 and 2 is interpreted as the primary formation of 7, which, under the reaction conditions, reacts with Me2NH to yield the secondary products 5, 6, and 8 (Scheme 7).
Helvetica Chimica Acta, 1995
Diphenyl phosphoraziddte (DPPA) was used as the azide source in a one-pot synthesis of 2,2-disubs... more Diphenyl phosphoraziddte (DPPA) was used as the azide source in a one-pot synthesis of 2,2-disubstituted 3-amino-2H-azirines 1 (Sc/zeme I). The reaction with lithium enolates of amides of type 2, bearing two substituents at C(2), proceeded smoothly in THF at 0"; keteniminium azides C and azidoenamines D are likely intermediates. Under analogous reaction conditions, DPPA and amides of type 3 with only one substituent at C(2) gave 2-diazoamides 5 in fair-to-good yield (Scheme 2). The corresponding 2-diazo derivatives 6-8 were formed in low yield by treatment of the lithium enolates of N,N-dimethyl-2-phenylacetamide, methyl 2-phenylacetate, and benzyl phenyl ketone, respectively, with DPPA. Thermolysis of 2-diazo-N-methyl-N-phenylcarboxamides 5a and 5b yielded 3-substituted 1,3-dihydro-N-methyl-2H-indol-2-ones 9a and 9b, respectively (Scheme 3). The diazo compounds 5 8 reacted with 1,3-thiazole-5 (4H)-thiones 10 and thiobenzophenone (13) to give 6-oxa-1,9-dithia-3-azaspiro[4.4]nona-2,7-dienes 11 (Scheme 4) and thiirane-2-cdrboxylic acid derivatives 14 (Scheme 5), respectively. In analogy to previously described reactions, a mechanism via 1,3-dipolar cycloaddition, leading to 2,5-dihydro-l,3,4thiadiazoles, and elimination of N2 to give the 'thiocarbonyl ylides' of type H or K is proposed. These dipolar intermediates with a conjugated C=O group then undergo either a 1,S-dipolar electrocyclization to give spiroheterocycles 11 or a 1,3-dipolar electrocyclization to thiiranes 14. ') *) 3,
Synthesis of Triazolo[1,5-a]triazin-7-one Derivatives and Highly Functionalized[1,2,4]Triazoles
Helvetica Chimica Acta, 2003
Introduction. ± Heteroaromatic nucleophilic addition/elimination reactions are commonly recognize... more Introduction. ± Heteroaromatic nucleophilic addition/elimination reactions are commonly recognized in many electron-deficient heterocycles [1]. However, analogous reactions with electron-rich heterocycles are rather uncommon [2]. On the other hand, alkyl-or arylsulfinyl, or alkyl-or ...
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Papers by Jose M. Villalgordo