After the structure originally proposed for nitraraine was shown to be incorrect by total synthes... more After the structure originally proposed for nitraraine was shown to be incorrect by total synthesis, the alternative structure 5 was recently suggested for the alkaloid on biosynthetic grounds and by comparison with the 1 H NMR data of tangutorine. The unambiguous synthesis of 5 is reported from tryptophanol and ketodiester 6, via oxazoloquinolone lactam 7. However, the melting point and 1 H NMR data of 5 did not match those reported for the natural product. Nitraraine 1 is an indole alkaloid isolated in 1985 from Nitraria schoberi L., collected in Kyzyl-Kum (Uzbekistan). On the basis of its mass-spectrometric fragmentation, spectroscopic UV, IR and 1 H NMR data, chemical transformations and correlations, and degradation studies, the yohimbane-type structure 1 was assigned to nitraraine
The enantioselective synthesis (3.7% overall yield in nine steps from 2) and biological screening... more The enantioselective synthesis (3.7% overall yield in nine steps from 2) and biological screening of the ethyl analog of the macrocyclic marine alkaloid haliclorensin C (compound 5) are reported. Amino alcohol 3, generated by a LiNH2BH3-promoted reductive ring-opening/debenzylation sequence from phenylglycinol-derived lactam 2, was used as the starting chiral linear building block. Incorporation of the undecene chain via the nosyl derivative 12, methylenation of the pentanol moiety, and a ring-closing metathesis are the key steps of the synthesis.
Corpora amylacea are spherical bodies of unknown origin and function, which accumulate in the hum... more Corpora amylacea are spherical bodies of unknown origin and function, which accumulate in the human brain during the aging process and neurodegenerative disorders. In recent work, we reported that they contain some neo-epitopes that are recognized by natural IgMs, revealing a possible link between them and the natural immune system. Here, we performed an ultrastructural study complemented with confocal microscopy in order to shed light on the formation of corpora amylacea and to precisely localize the neo-epitopes. We show that immature corpora amylacea are intracellular astrocytic structures formed by profuse cellular debris and membranous blebs entrapped in a scattered mass of randomly oriented short linear fibers. In mature corpora amylacea, the structure becomes compacted and fibrillary material constitutes the principal component. We also determined that the neo-epitopes were uniformly localized throughout the whole structure. All these observations reinforce the idea that corpora amylacea of human brain are equivalent to another type of polyglucosan bodies named pAs granules, present in mouse brain and originated from degenerative processes. All those findings support the hypothesis that corpora amylacea are involved in the entrapment of damaged materials and nondegradable products and have a role in protective or cleaning mechanisms. Corpora amylacea (CA) are spherical or ovoid polyglucosan bodies (PGBs) that measure 2 to 20 μm in diameter and accumulate primarily in the periventricular and subpial regions of the human brain during the aging process and some neurodegenerative diseases 1,2. Although they were described by J.E. Purkinje as far back as 1837, their origin and function remain unknown. Several authors indicate that CA are located within astrocytic processes 3-6 , while others described them as intra-axonal inclusions 7-9. However, they have not been reported within neuronal perikarya. In any case, it seems that CA are seen less often within neuronal processes than within astrocytic processes 10. They are positive to periodic acid-Schiff (PAS) staining due to their high polysaccharide content, and when purified by a centrifugation procedure with final extraction in hot water, they yield a clear water-soluble fraction containing 87.9% hexose, 4.7% protein and 2.5% phosphate 2. As extensively reviewed in Augé et al. 11 , the presence of numerous different types of proteins has been described in CA, including (among others) tau protein, amyloid-β peptides, β-tubulin, glial fibrillary acidic protein (GFAP), microtubule-associated protein 2, neuronal nuclei (NeuN) protein, synuclein, S100β, aquaporin 4, ubiquitin, reelin, nestin and some fungal components. As also indicated in Augé et al. 11 , the presence of these (and other) components is supported in some studies, but ruled out in others.
Dedication ((optional)) A variety of (R)-phenylglycinol-derived oxazolopiperidone lactams (1-14) ... more Dedication ((optional)) A variety of (R)-phenylglycinol-derived oxazolopiperidone lactams (1-14) are converted to linear-chain enantiopure aminodiols (15-26) by reduction with LiNH2BH3 in an unprecedented process involving the simultaneous reductive opening of the oxazolidine and lactam rings. The subsequent removal of the phenylethanol moiety gave enantiopure 5-amino-1-pentanols bearing substituents at the 2-, 3-, 4-, 2,2-, 2,3-2,4-and 3,4-positions (28-36), which were isolated as the N-Boc derivatives.
The configuration of (3R,8aS)-5-oxo-3-phenyl-2,3,6,7,8,8a-hexahydro-5H-oxazolo[3,2-a]pyridine 2 h... more The configuration of (3R,8aS)-5-oxo-3-phenyl-2,3,6,7,8,8a-hexahydro-5H-oxazolo[3,2-a]pyridine 2 has been unambiguously confirmed by X-ray crystallographic analysis. A 1 H NMR-based method for the stereochemical assignment of 3,8a-cis and trans phenylglycinol-derived bicyclic lactams is also proposed.
The prcpnration of ch&al cis-and fruns-oxaxo~opipezidones 1,2, and 3 by aitomativc procedures sod... more The prcpnration of ch&al cis-and fruns-oxaxo~opipezidones 1,2, and 3 by aitomativc procedures sod XIII
specializes in the rapid dissemination of high-quality studies of crystal and molecular structure... more specializes in the rapid dissemination of high-quality studies of crystal and molecular structures of interest in fields such as chemistry, biochemistry, mineralogy, pharmacology, physics and materials science. The numerical and text descriptions of each structure are submitted to the journal electronically as a Crystallographic Information File (CIF) and are checked and typeset automatically prior to peer review. The journal is well known for its high standards of structural reliability and presentation. Section C publishes approximately 1000 structures per year; readers have access to an archive that includes high-quality structural data for over 10000 compounds. Crystallography Journals Online is available from journals.iucr.org Acta Cryst. (2012). C68, o114-o118 Mata et al. • C 8 H 9 NO 2
Diastereoselective syntheses O 0031 Stereoselective α-Amidoalkylation of Phenylglycinol-Derived L... more Diastereoselective syntheses O 0031 Stereoselective α-Amidoalkylation of Phenylglycinol-Derived Lactams. Synthesis of Enantiopure 5,6-Disubstituted 2-Piperidones.-The stereochemical outcome of the α-amidoalkylation of title lactams (I) and (X) is controlled by the alkylation conditions. Thus, Ti(IV)-mediated alkylations proceed with inversion of stereochemistry at the C-8a center in most cases [cf. (III), (XIII)], while the reactions with Grignard reagents afford the products (VI) and (XI) with retention of C-8a configuration.
The addition of the enolate of methyl 1-methyl-2-indoleacetate 1 and lithium 2-(lithiomethyl)indo... more The addition of the enolate of methyl 1-methyl-2-indoleacetate 1 and lithium 2-(lithiomethyl)indole-1-carboxylate 5 to pyridines and N-alkylpyridinium salts bearing a chiral auxiliary at the 3-position (tolylsulfinyl, acyl iron complexes, bornane-10,2sultam), with subsequent acid cyclization of the resulting dihydropyridines, is investigated.
The diastereomeric phenylglycinol-derived unsaturated d-lactams trans-3 and cis-3 react with dien... more The diastereomeric phenylglycinol-derived unsaturated d-lactams trans-3 and cis-3 react with dienes with exo facial diastereoselectivity to give the corresponding tricyclic adducts, which were ultimately converted to enantiomeric cis-hydroisoquinolines.
The preparation of 4-, 5-, and 6-methoxy substituted 3-lithio-1-(trialkylsilyl)indoles 4b-d by me... more The preparation of 4-, 5-, and 6-methoxy substituted 3-lithio-1-(trialkylsilyl)indoles 4b-d by metalation of the corresponding 3-bromoindoles, and their reactions with iodomethane, DMF, ethylene oxide and aziridines are reported. Transmetalation of 3-lithioindoles 4b-d with ZnCl 2 afforded 3-indolylzinc chlorides 11b-d, which underwent Pd(0)-catalyzed cross-coupling reactions with 2-halopyridines to give 4-, 5-, and 6-methoxy substituted 3-(2pyridyl)indoles.
Starting from 4-substituted cyclohexanones, a practical synthetic route to enantiopure 6-substitu... more Starting from 4-substituted cyclohexanones, a practical synthetic route to enantiopure 6-substituted cis-decahydroquinolines has been developed, the key steps being a stereoselective cyclocondensation of an unsaturated δ-keto ester derivative with (R)-phenylglycinol and the stereoselective hydrogenation of the resulting tricyclic oxazoloquinolone lactams.
After the structure originally proposed for nitraraine was shown to be incorrect by total synthes... more After the structure originally proposed for nitraraine was shown to be incorrect by total synthesis, the alternative structure 5 was recently suggested for the alkaloid on biosynthetic grounds and by comparison with the 1 H NMR data of tangutorine. The unambiguous synthesis of 5 is reported from tryptophanol and ketodiester 6, via oxazoloquinolone lactam 7. However, the melting point and 1 H NMR data of 5 did not match those reported for the natural product. Nitraraine 1 is an indole alkaloid isolated in 1985 from Nitraria schoberi L., collected in Kyzyl-Kum (Uzbekistan). On the basis of its mass-spectrometric fragmentation, spectroscopic UV, IR and 1 H NMR data, chemical transformations and correlations, and degradation studies, the yohimbane-type structure 1 was assigned to nitraraine
The enantioselective synthesis (3.7% overall yield in nine steps from 2) and biological screening... more The enantioselective synthesis (3.7% overall yield in nine steps from 2) and biological screening of the ethyl analog of the macrocyclic marine alkaloid haliclorensin C (compound 5) are reported. Amino alcohol 3, generated by a LiNH2BH3-promoted reductive ring-opening/debenzylation sequence from phenylglycinol-derived lactam 2, was used as the starting chiral linear building block. Incorporation of the undecene chain via the nosyl derivative 12, methylenation of the pentanol moiety, and a ring-closing metathesis are the key steps of the synthesis.
Corpora amylacea are spherical bodies of unknown origin and function, which accumulate in the hum... more Corpora amylacea are spherical bodies of unknown origin and function, which accumulate in the human brain during the aging process and neurodegenerative disorders. In recent work, we reported that they contain some neo-epitopes that are recognized by natural IgMs, revealing a possible link between them and the natural immune system. Here, we performed an ultrastructural study complemented with confocal microscopy in order to shed light on the formation of corpora amylacea and to precisely localize the neo-epitopes. We show that immature corpora amylacea are intracellular astrocytic structures formed by profuse cellular debris and membranous blebs entrapped in a scattered mass of randomly oriented short linear fibers. In mature corpora amylacea, the structure becomes compacted and fibrillary material constitutes the principal component. We also determined that the neo-epitopes were uniformly localized throughout the whole structure. All these observations reinforce the idea that corpora amylacea of human brain are equivalent to another type of polyglucosan bodies named pAs granules, present in mouse brain and originated from degenerative processes. All those findings support the hypothesis that corpora amylacea are involved in the entrapment of damaged materials and nondegradable products and have a role in protective or cleaning mechanisms. Corpora amylacea (CA) are spherical or ovoid polyglucosan bodies (PGBs) that measure 2 to 20 μm in diameter and accumulate primarily in the periventricular and subpial regions of the human brain during the aging process and some neurodegenerative diseases 1,2. Although they were described by J.E. Purkinje as far back as 1837, their origin and function remain unknown. Several authors indicate that CA are located within astrocytic processes 3-6 , while others described them as intra-axonal inclusions 7-9. However, they have not been reported within neuronal perikarya. In any case, it seems that CA are seen less often within neuronal processes than within astrocytic processes 10. They are positive to periodic acid-Schiff (PAS) staining due to their high polysaccharide content, and when purified by a centrifugation procedure with final extraction in hot water, they yield a clear water-soluble fraction containing 87.9% hexose, 4.7% protein and 2.5% phosphate 2. As extensively reviewed in Augé et al. 11 , the presence of numerous different types of proteins has been described in CA, including (among others) tau protein, amyloid-β peptides, β-tubulin, glial fibrillary acidic protein (GFAP), microtubule-associated protein 2, neuronal nuclei (NeuN) protein, synuclein, S100β, aquaporin 4, ubiquitin, reelin, nestin and some fungal components. As also indicated in Augé et al. 11 , the presence of these (and other) components is supported in some studies, but ruled out in others.
Dedication ((optional)) A variety of (R)-phenylglycinol-derived oxazolopiperidone lactams (1-14) ... more Dedication ((optional)) A variety of (R)-phenylglycinol-derived oxazolopiperidone lactams (1-14) are converted to linear-chain enantiopure aminodiols (15-26) by reduction with LiNH2BH3 in an unprecedented process involving the simultaneous reductive opening of the oxazolidine and lactam rings. The subsequent removal of the phenylethanol moiety gave enantiopure 5-amino-1-pentanols bearing substituents at the 2-, 3-, 4-, 2,2-, 2,3-2,4-and 3,4-positions (28-36), which were isolated as the N-Boc derivatives.
The configuration of (3R,8aS)-5-oxo-3-phenyl-2,3,6,7,8,8a-hexahydro-5H-oxazolo[3,2-a]pyridine 2 h... more The configuration of (3R,8aS)-5-oxo-3-phenyl-2,3,6,7,8,8a-hexahydro-5H-oxazolo[3,2-a]pyridine 2 has been unambiguously confirmed by X-ray crystallographic analysis. A 1 H NMR-based method for the stereochemical assignment of 3,8a-cis and trans phenylglycinol-derived bicyclic lactams is also proposed.
The prcpnration of ch&al cis-and fruns-oxaxo~opipezidones 1,2, and 3 by aitomativc procedures sod... more The prcpnration of ch&al cis-and fruns-oxaxo~opipezidones 1,2, and 3 by aitomativc procedures sod XIII
specializes in the rapid dissemination of high-quality studies of crystal and molecular structure... more specializes in the rapid dissemination of high-quality studies of crystal and molecular structures of interest in fields such as chemistry, biochemistry, mineralogy, pharmacology, physics and materials science. The numerical and text descriptions of each structure are submitted to the journal electronically as a Crystallographic Information File (CIF) and are checked and typeset automatically prior to peer review. The journal is well known for its high standards of structural reliability and presentation. Section C publishes approximately 1000 structures per year; readers have access to an archive that includes high-quality structural data for over 10000 compounds. Crystallography Journals Online is available from journals.iucr.org Acta Cryst. (2012). C68, o114-o118 Mata et al. • C 8 H 9 NO 2
Diastereoselective syntheses O 0031 Stereoselective α-Amidoalkylation of Phenylglycinol-Derived L... more Diastereoselective syntheses O 0031 Stereoselective α-Amidoalkylation of Phenylglycinol-Derived Lactams. Synthesis of Enantiopure 5,6-Disubstituted 2-Piperidones.-The stereochemical outcome of the α-amidoalkylation of title lactams (I) and (X) is controlled by the alkylation conditions. Thus, Ti(IV)-mediated alkylations proceed with inversion of stereochemistry at the C-8a center in most cases [cf. (III), (XIII)], while the reactions with Grignard reagents afford the products (VI) and (XI) with retention of C-8a configuration.
The addition of the enolate of methyl 1-methyl-2-indoleacetate 1 and lithium 2-(lithiomethyl)indo... more The addition of the enolate of methyl 1-methyl-2-indoleacetate 1 and lithium 2-(lithiomethyl)indole-1-carboxylate 5 to pyridines and N-alkylpyridinium salts bearing a chiral auxiliary at the 3-position (tolylsulfinyl, acyl iron complexes, bornane-10,2sultam), with subsequent acid cyclization of the resulting dihydropyridines, is investigated.
The diastereomeric phenylglycinol-derived unsaturated d-lactams trans-3 and cis-3 react with dien... more The diastereomeric phenylglycinol-derived unsaturated d-lactams trans-3 and cis-3 react with dienes with exo facial diastereoselectivity to give the corresponding tricyclic adducts, which were ultimately converted to enantiomeric cis-hydroisoquinolines.
The preparation of 4-, 5-, and 6-methoxy substituted 3-lithio-1-(trialkylsilyl)indoles 4b-d by me... more The preparation of 4-, 5-, and 6-methoxy substituted 3-lithio-1-(trialkylsilyl)indoles 4b-d by metalation of the corresponding 3-bromoindoles, and their reactions with iodomethane, DMF, ethylene oxide and aziridines are reported. Transmetalation of 3-lithioindoles 4b-d with ZnCl 2 afforded 3-indolylzinc chlorides 11b-d, which underwent Pd(0)-catalyzed cross-coupling reactions with 2-halopyridines to give 4-, 5-, and 6-methoxy substituted 3-(2pyridyl)indoles.
Starting from 4-substituted cyclohexanones, a practical synthetic route to enantiopure 6-substitu... more Starting from 4-substituted cyclohexanones, a practical synthetic route to enantiopure 6-substituted cis-decahydroquinolines has been developed, the key steps being a stereoselective cyclocondensation of an unsaturated δ-keto ester derivative with (R)-phenylglycinol and the stereoselective hydrogenation of the resulting tricyclic oxazoloquinolone lactams.
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