Abdallah Hamze - Academia.edu (original) (raw)
Papers by Abdallah Hamze
Comprehensive Organic Synthesis II, 2014
The Journal of Organic Chemistry, 2014
The synthesis of amino-substituted N-vinylazoles was achieved by a new palladium-assisted tandem ... more The synthesis of amino-substituted N-vinylazoles was achieved by a new palladium-assisted tandem catalytic reaction involving N-tosylhydrazones, halo-substituted azoles, and amines. Accordingly, two Csp 2 −N bonds were formed through two mechanistically distinct reactions using a single Pd II /Pd 0 catalyst system in a one-pot fashion. This work paves the way for the design of biological relevant compounds in an amino-substituted N-vinylindole series. Among several polyoxygenated derivatives evaluated, compounds 5e and 5u were found to exhibit good antiproliferative activity.
![Research paper thumbnail of Synthesis of a 3-(α-Styryl)benzo[ b ]-thiophene Library via Bromocyclization of Alkynes and Palladium-Catalyzed Tosylhydrazones Cross-Couplings: Evaluation as Antitubulin Agents](https://attachments.academia-assets.com/47413658/thumbnails/1.jpg)
](ACS Combinatorial Science, 2014
A library of functionalized 3-(α-styryl)-benzo- [b]thiophenes, endowed with a high level of molec... more A library of functionalized 3-(α-styryl)-benzo- [b]thiophenes, endowed with a high level of molecular diversity, was efficiently synthesized by applying a synthetic sequence that allowed introduction of various substituents on aromatic A, B, and C-rings. The strategy developed involves the synthesis of 3-bromobenzo[b]thiophene derivatives through a bromocyclization step of methylthio-containing alkynes using N-methylpyrrolidin-2-one hydrotribromide reagent (MPHT). Further coupling of 3-bromobenzothiophenes under palladium-catalysis with N-tosylhydrazones efficiently furnished 2-aryl-3-(α-styryl)benzo[b]thiophene derivatives. The antiproliferative properties of target compounds were studied. Among them, compound 5m has demonstrated submicromolar cytotoxic activity against HCT-116 cell line, and inhibited the polymerization of tubulin at micromolar level comparable to that of CA-4.
European Journal of Medicinal Chemistry, 2015
Potent anticancer 4-arylchromene agents 6, as restricted isoCA-4 analogues, were prepared with ex... more Potent anticancer 4-arylchromene agents 6, as restricted isoCA-4 analogues, were prepared with excellent yields by a rapid and versatile synthetic pathway. First, in the presence of PTSA in EtOH, a variety of arylalkynols 9 were transformed into substituted 4-chromanones 10 in a one pot procedure which include regioselective arylalkynols hydration, alcohol etherification, MOM-cleavage, and cyclization. Further palladium coupling reactions, using aryl halides and N-tosylhydrazones 11 gave access to a small library of functionalized 4-arylchromenes 6 with good yields. From this series of 4-arylchromenes, we have identified compound 6s which inhibit tubulin assembly at a micromolar level and demonstrate a remarkable nanomolar level of cytotoxicity against four human cancer cell lines. Docking studies showed that isoCA-4 and its restricted chromene analogue 6s adopt a similar positioning in the colchicine binding-site of tubulin.
ACS Catalysis, 2014
ABSTRACT An original formation of one C–N bond and one C–C bond on the same carbenic center has b... more ABSTRACT An original formation of one C–N bond and one C–C bond on the same carbenic center has been developed. This approach involves a copper-catalyzed cross-coupling reaction between 2′-bromo-biaryl-N-tosylhydrazones and different amines leading to 9H-fluoren-9-amine derivatives. This reaction proceeds under mild conditions in glycerol, an inexpensive and environmentally friendly solvent, without adding any external ligand.Keywords: N-tosylhydrazones; C−N/C−C bond formation; autotandem catalysis; carbenoid; fluoren-9H-amines
Tetrahedron Letters, 2011
A convenient and efficient procedure for the synthesis of 4-arylchromenes, thiochromenes, and rel... more A convenient and efficient procedure for the synthesis of 4-arylchromenes, thiochromenes, and related heterocycles via a four step-sequence has been developed. The first three steps, which involve hydration of alkynes, hydrazones formation, and their Pd-coupling with ortho substituted aryl halides, furnished stereoselectively Z-trisubstituted olefins without any purification of the intermediates generated in each stage. These latter proved to be suitable precursors, in the last step, for the synthesis of the desired heterocycles of biological interest.
ChemInform, 2012
Rapid and versatile access to (Z)-trisubstituted olefins 2 and their cyclization into 4-aryl-2H-c... more Rapid and versatile access to (Z)-trisubstituted olefins 2 and their cyclization into 4-aryl-2H-chromenes 1 starting from arylalkynes 3 is described. In a one-pot fashion, alkynes 3 were first hydrated, then transformed into N-tosylhydrazones, and finally coupled with ortho-substituted aryl halides under palladium catalysis to give trisubstituted olefins 2 in good yields and very high to total Z selectivity. 1,1-Diaryl-[a] 1605 Scheme 1. Proposed mechanism for the synthesis of 2d from 3a or 3d. www.eurjoc.org 1606 Scheme 2. Synthesis of 4 from alkynol 3b.
ChemInform, 2011
A series of functionalized 2-(1-phenylvinyl)benzofurans 2 and 2-(1-phenylvinyl)indoles 3 were pre... more A series of functionalized 2-(1-phenylvinyl)benzofurans 2 and 2-(1-phenylvinyl)indoles 3 were prepared from 1-phenylvinyl iodides and silylated alkynes in a one-pot reaction. After a desilylation step, the Sonogashira coupling reaction between the resulting terminal alkynes and 1-phenylvinyl iodide derivatives 6 gave enyne intermediates, which underwent a 5-endo-dig cyclization to afford 2-(1-phenylvinyl) het-
ChemInform, 2008
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform, 2010
Palladium-catalyzed hydrostannation reactions of ortho-disubstituted arylalkynes were achieved wi... more Palladium-catalyzed hydrostannation reactions of ortho-disubstituted arylalkynes were achieved with total stereo-and regio-selectivity in THF at room temperature. The regioselectivity was found to be under the control of the ortho-substituents (ortho-directing effects, ODE) and pure a-vinylstannanes are produced in good yields and as single isomers regardless of the substituents' nature. These hydrostannation a-products are precursors of choice for the preparation of stereo-defined triarylolefins.
ChemInform, 2010
PdCl 2 (MeCN) 2 in combination with dppp proved to be a powerful and efficient catalyst for the c... more PdCl 2 (MeCN) 2 in combination with dppp proved to be a powerful and efficient catalyst for the coupling of sterically hindered N-arylsulfonylhydrazones with aryl halides, thus providing a flexible and convergent access to tetrasubstituted olefins related to iso-combretastatin A4 in good yields. This new protocol has been applied successfully to the formal synthesis of biphenylisopropylidene 4-pyridine CYP17 inhibitor, 12b, of biological interest.
![Research paper thumbnail of ChemInform Abstract: MPHT-Promoted Bromocyclization of ortho-Substituted Arylalkynes: Application to the Synthesis of 2-Substituted 3-Bromobenzofurans and -Benzo[b]thiophenes](https://attachments.academia-assets.com/47413667/thumbnails/1.jpg)
](ChemInform, 2010
A convenient and general approach to the synthesis of 2substituted 3-bromobenzofurans and -benzot... more A convenient and general approach to the synthesis of 2substituted 3-bromobenzofurans and -benzothiophenes was developed. The procedure is based on the cyclization of ortho-substituted arylalkynes in the presence of N-methylpyrrolidin-2-one hydrotribromide (MPHT) as a soft and easy-tohandle electrophilic brominating reagent. Under mild reaction conditions, MPHT promoted the bromocyclization of [a]
Advances in Experimental Medicine and Biology, 2009
ChemInform, 2008
Subsequent coupling of the benzil products with diverse amino compounds allows an easy access to ... more Subsequent coupling of the benzil products with diverse amino compounds allows an easy access to quinoxalines, imidazoles, and imidazolidinediones. -(MOUSSET, C.; PROVOT*, O.; HAMZE, A.; BIGNON, J.; BRION, J.-D.; ALAMI, M.; Tetrahedron 64 (2008) 19, 4287-4294; Lab. Chim. Therap., Fac. Pharm., BIOCIS, Univ. Paris-Sud, F-92296 Chatenay-Malabry, Fr.; Eng.) -Jannicke 39-080
ChemInform, 2012
An efficient access to 1,1-diarylethylenes of biological interest by coupling functionalized aryl... more An efficient access to 1,1-diarylethylenes of biological interest by coupling functionalized aryl Grignard reagents and 1-arylvinyl halides in the presence of FeCl 3 /CuTC is described. This bimetallic system proved to be superior to the use of Fe or Cu catalyst alone. The synthetic utility of this protocol is illustrated in the field of steroid chemistry.
Tetrahedron Letters, 2005
A method for the solid phase synthesis of substituted arginine containing peptides starting from ... more A method for the solid phase synthesis of substituted arginine containing peptides starting from an isothiocitrulline precursor is described. In this procedure, a peptide containing one or more protected ornithine residue(s) was assembled on a solid support. Following selective deprotection, ornithine residue(s) was (were) converted into S-methyl-isothiocitrulline in three steps. Subsequent reaction with primary or secondary amines afforded mono and disubstituted arginine-containing derivatives, respectively. Using lysine instead of ornithine afforded substituted homoarginine-containing derivatives.
ChemInform, 2004
Synthesis of Various 3-Substituted 1,2,4-Oxadiazole-Containing Chiral β 3 -and α-Amino Acids from... more Synthesis of Various 3-Substituted 1,2,4-Oxadiazole-Containing Chiral β 3 -and α-Amino Acids from Fmoc-Protected Aspartic Acid. -A simple protocol is developed for the construction of the title oxadiazole-containing amino acids (V) and (IX) starting from Fmoc-protected aspartic acid monoesters (I) and (VI), respectively. O-Acylation of amidoximes (II) with the monoesters and subsequent NaOAc-mediated ring closure provides the oxadiazole ring in good yields. -(HAMZE, A.; HERNANDEZ*, J.-F.; FULCRAND, P.; MARTINEZ, J.; J. Org. Chem. 68 (2003) 19, 7316-7321; Lab. Amino-Acides Pept. Prot., Fac. Pharm., CNRS, Univ. Montpellier I, F-34095 Montpellier, Fr.; Eng.) -Mischke 07-163
Comprehensive Organic Synthesis II, 2014
The Journal of Organic Chemistry, 2014
The synthesis of amino-substituted N-vinylazoles was achieved by a new palladium-assisted tandem ... more The synthesis of amino-substituted N-vinylazoles was achieved by a new palladium-assisted tandem catalytic reaction involving N-tosylhydrazones, halo-substituted azoles, and amines. Accordingly, two Csp 2 −N bonds were formed through two mechanistically distinct reactions using a single Pd II /Pd 0 catalyst system in a one-pot fashion. This work paves the way for the design of biological relevant compounds in an amino-substituted N-vinylindole series. Among several polyoxygenated derivatives evaluated, compounds 5e and 5u were found to exhibit good antiproliferative activity.
ACS Combinatorial Science, 2014
A library of functionalized 3-(α-styryl)-benzo- [b]thiophenes, endowed with a high level of molec... more A library of functionalized 3-(α-styryl)-benzo- [b]thiophenes, endowed with a high level of molecular diversity, was efficiently synthesized by applying a synthetic sequence that allowed introduction of various substituents on aromatic A, B, and C-rings. The strategy developed involves the synthesis of 3-bromobenzo[b]thiophene derivatives through a bromocyclization step of methylthio-containing alkynes using N-methylpyrrolidin-2-one hydrotribromide reagent (MPHT). Further coupling of 3-bromobenzothiophenes under palladium-catalysis with N-tosylhydrazones efficiently furnished 2-aryl-3-(α-styryl)benzo[b]thiophene derivatives. The antiproliferative properties of target compounds were studied. Among them, compound 5m has demonstrated submicromolar cytotoxic activity against HCT-116 cell line, and inhibited the polymerization of tubulin at micromolar level comparable to that of CA-4.
European Journal of Medicinal Chemistry, 2015
Potent anticancer 4-arylchromene agents 6, as restricted isoCA-4 analogues, were prepared with ex... more Potent anticancer 4-arylchromene agents 6, as restricted isoCA-4 analogues, were prepared with excellent yields by a rapid and versatile synthetic pathway. First, in the presence of PTSA in EtOH, a variety of arylalkynols 9 were transformed into substituted 4-chromanones 10 in a one pot procedure which include regioselective arylalkynols hydration, alcohol etherification, MOM-cleavage, and cyclization. Further palladium coupling reactions, using aryl halides and N-tosylhydrazones 11 gave access to a small library of functionalized 4-arylchromenes 6 with good yields. From this series of 4-arylchromenes, we have identified compound 6s which inhibit tubulin assembly at a micromolar level and demonstrate a remarkable nanomolar level of cytotoxicity against four human cancer cell lines. Docking studies showed that isoCA-4 and its restricted chromene analogue 6s adopt a similar positioning in the colchicine binding-site of tubulin.
ACS Catalysis, 2014
ABSTRACT An original formation of one C–N bond and one C–C bond on the same carbenic center has b... more ABSTRACT An original formation of one C–N bond and one C–C bond on the same carbenic center has been developed. This approach involves a copper-catalyzed cross-coupling reaction between 2′-bromo-biaryl-N-tosylhydrazones and different amines leading to 9H-fluoren-9-amine derivatives. This reaction proceeds under mild conditions in glycerol, an inexpensive and environmentally friendly solvent, without adding any external ligand.Keywords: N-tosylhydrazones; C−N/C−C bond formation; autotandem catalysis; carbenoid; fluoren-9H-amines
Tetrahedron Letters, 2011
A convenient and efficient procedure for the synthesis of 4-arylchromenes, thiochromenes, and rel... more A convenient and efficient procedure for the synthesis of 4-arylchromenes, thiochromenes, and related heterocycles via a four step-sequence has been developed. The first three steps, which involve hydration of alkynes, hydrazones formation, and their Pd-coupling with ortho substituted aryl halides, furnished stereoselectively Z-trisubstituted olefins without any purification of the intermediates generated in each stage. These latter proved to be suitable precursors, in the last step, for the synthesis of the desired heterocycles of biological interest.
ChemInform, 2012
Rapid and versatile access to (Z)-trisubstituted olefins 2 and their cyclization into 4-aryl-2H-c... more Rapid and versatile access to (Z)-trisubstituted olefins 2 and their cyclization into 4-aryl-2H-chromenes 1 starting from arylalkynes 3 is described. In a one-pot fashion, alkynes 3 were first hydrated, then transformed into N-tosylhydrazones, and finally coupled with ortho-substituted aryl halides under palladium catalysis to give trisubstituted olefins 2 in good yields and very high to total Z selectivity. 1,1-Diaryl-[a] 1605 Scheme 1. Proposed mechanism for the synthesis of 2d from 3a or 3d. www.eurjoc.org 1606 Scheme 2. Synthesis of 4 from alkynol 3b.
ChemInform, 2011
A series of functionalized 2-(1-phenylvinyl)benzofurans 2 and 2-(1-phenylvinyl)indoles 3 were pre... more A series of functionalized 2-(1-phenylvinyl)benzofurans 2 and 2-(1-phenylvinyl)indoles 3 were prepared from 1-phenylvinyl iodides and silylated alkynes in a one-pot reaction. After a desilylation step, the Sonogashira coupling reaction between the resulting terminal alkynes and 1-phenylvinyl iodide derivatives 6 gave enyne intermediates, which underwent a 5-endo-dig cyclization to afford 2-(1-phenylvinyl) het-
ChemInform, 2008
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform, 2010
Palladium-catalyzed hydrostannation reactions of ortho-disubstituted arylalkynes were achieved wi... more Palladium-catalyzed hydrostannation reactions of ortho-disubstituted arylalkynes were achieved with total stereo-and regio-selectivity in THF at room temperature. The regioselectivity was found to be under the control of the ortho-substituents (ortho-directing effects, ODE) and pure a-vinylstannanes are produced in good yields and as single isomers regardless of the substituents' nature. These hydrostannation a-products are precursors of choice for the preparation of stereo-defined triarylolefins.
ChemInform, 2010
PdCl 2 (MeCN) 2 in combination with dppp proved to be a powerful and efficient catalyst for the c... more PdCl 2 (MeCN) 2 in combination with dppp proved to be a powerful and efficient catalyst for the coupling of sterically hindered N-arylsulfonylhydrazones with aryl halides, thus providing a flexible and convergent access to tetrasubstituted olefins related to iso-combretastatin A4 in good yields. This new protocol has been applied successfully to the formal synthesis of biphenylisopropylidene 4-pyridine CYP17 inhibitor, 12b, of biological interest.
ChemInform, 2010
A convenient and general approach to the synthesis of 2substituted 3-bromobenzofurans and -benzot... more A convenient and general approach to the synthesis of 2substituted 3-bromobenzofurans and -benzothiophenes was developed. The procedure is based on the cyclization of ortho-substituted arylalkynes in the presence of N-methylpyrrolidin-2-one hydrotribromide (MPHT) as a soft and easy-tohandle electrophilic brominating reagent. Under mild reaction conditions, MPHT promoted the bromocyclization of [a]
Advances in Experimental Medicine and Biology, 2009
ChemInform, 2008
Subsequent coupling of the benzil products with diverse amino compounds allows an easy access to ... more Subsequent coupling of the benzil products with diverse amino compounds allows an easy access to quinoxalines, imidazoles, and imidazolidinediones. -(MOUSSET, C.; PROVOT*, O.; HAMZE, A.; BIGNON, J.; BRION, J.-D.; ALAMI, M.; Tetrahedron 64 (2008) 19, 4287-4294; Lab. Chim. Therap., Fac. Pharm., BIOCIS, Univ. Paris-Sud, F-92296 Chatenay-Malabry, Fr.; Eng.) -Jannicke 39-080
ChemInform, 2012
An efficient access to 1,1-diarylethylenes of biological interest by coupling functionalized aryl... more An efficient access to 1,1-diarylethylenes of biological interest by coupling functionalized aryl Grignard reagents and 1-arylvinyl halides in the presence of FeCl 3 /CuTC is described. This bimetallic system proved to be superior to the use of Fe or Cu catalyst alone. The synthetic utility of this protocol is illustrated in the field of steroid chemistry.
Tetrahedron Letters, 2005
A method for the solid phase synthesis of substituted arginine containing peptides starting from ... more A method for the solid phase synthesis of substituted arginine containing peptides starting from an isothiocitrulline precursor is described. In this procedure, a peptide containing one or more protected ornithine residue(s) was assembled on a solid support. Following selective deprotection, ornithine residue(s) was (were) converted into S-methyl-isothiocitrulline in three steps. Subsequent reaction with primary or secondary amines afforded mono and disubstituted arginine-containing derivatives, respectively. Using lysine instead of ornithine afforded substituted homoarginine-containing derivatives.
ChemInform, 2004
Synthesis of Various 3-Substituted 1,2,4-Oxadiazole-Containing Chiral β 3 -and α-Amino Acids from... more Synthesis of Various 3-Substituted 1,2,4-Oxadiazole-Containing Chiral β 3 -and α-Amino Acids from Fmoc-Protected Aspartic Acid. -A simple protocol is developed for the construction of the title oxadiazole-containing amino acids (V) and (IX) starting from Fmoc-protected aspartic acid monoesters (I) and (VI), respectively. O-Acylation of amidoximes (II) with the monoesters and subsequent NaOAc-mediated ring closure provides the oxadiazole ring in good yields. -(HAMZE, A.; HERNANDEZ*, J.-F.; FULCRAND, P.; MARTINEZ, J.; J. Org. Chem. 68 (2003) 19, 7316-7321; Lab. Amino-Acides Pept. Prot., Fac. Pharm., CNRS, Univ. Montpellier I, F-34095 Montpellier, Fr.; Eng.) -Mischke 07-163