ABSTRACT
The application of the most representative and up-to-date examples of homogeneous asymmetric organocatalysis to the synthesis of molecules of interest in medicinal chemistry is reported. The use of different types of organocatalysts operative via noncovalent and covalent interactions is critically reviewed and the possibility of running some of these reactions on large or industrial scale is described. A comparison between the organo- and metal-catalysed methodologies is offered in several cases, thus highlighting the merits and drawbacks of these two complementary approaches to the obtainment of very popular on market drugs or of related key scaffolds.
ABSTRACT
Several small organic molecule catalysts are reminiscent of natural enzymes in their mode of action and substrate interaction/activation. This striking similarity has been a great source of inspiration for the development of new organocatalytic asymmetric processes. A few representative examples, mostly dealing with catalysts interacting through multiple hydrogen-bonds (synthetic oxyanion holes), are highlighted in this perspective.
Subject(s)
Biomimetic Materials/chemistry , Amination , Catalysis , Catalytic Domain , Cyclization , Esterases/chemistry , Hydrogen Bonding , Protein Binding , Serine Proteases/chemistry , Stereoisomerism , Thiourea/analogs & derivatives , Thiourea/chemical synthesis , Thiourea/chemistry , Urea/analogs & derivatives , Urea/chemical synthesis , Urea/chemistryABSTRACT
A new approach to additions of silicon nucleophiles to imines was developed. The method is based on the phase-transfer of phenoxides by ammonium catalysts, overcoming the inability of amide adducts in promoting the reactions.
Subject(s)
Amines/chemical synthesis , Hydrocarbons, Fluorinated/chemistry , Imines/chemistry , Organosilicon Compounds/chemistry , Oxides/chemistry , Quaternary Ammonium Compounds/chemistry , Amines/chemistry , Catalysis , Molecular Structure , Phase TransitionABSTRACT
Aerogel microspheres of chitosan, an abundant biopolymer obtained from marine crustaceans, have been successfully applied to catalyze the asymmetric aldol reaction in water, providing the products in high yields and with good stereoselectivity (up to 93% ee) and recyclability (up to 4 runs). Yields were favourably affected by additives such as DNP and stearic acid.
Subject(s)
Alcohols/chemical synthesis , Chitosan/chemistry , Gels/chemistry , Water/chemistry , Alcohols/chemistry , Animals , Catalysis , Crustacea/chemistry , Molecular Structure , StereoisomerismSubject(s)
Drug Carriers/chemistry , Hyperthermia, Induced/methods , Magnetic Resonance Imaging , Nanoparticles/chemistry , Neoplasms/diagnosis , Neoplasms/therapy , Serum Albumin, Bovine/metabolism , Animals , Cattle , Dextrans , Ferric Compounds/chemistry , Ferrosoferric Oxide/chemistry , Light , Liver , Magnetics , Magnetite Nanoparticles , Nanoparticles/ultrastructure , Rats , Scattering, RadiationABSTRACT
The asymmetric Povarov reaction of N-arylimines with 2- and 3-vinylindoles has been developed using a chiral phosphoric acid ((S)-TRIP) as catalyst. The peculiar reactivity of vinylindoles allowed also the disclosure of a Povarov Friedel-Crafts sequence, and the trapping of the reaction intermediate with nucleophilic species, thus providing a versatile platform for the preparation of highly enantioenriched indole derivatives.
Subject(s)
Alkanes/chemistry , Isoxazoles/chemistry , Nitro Compounds/chemistry , Catalysis , Molecular StructureABSTRACT
A novel organocatalytic formal [3 + 2] cycloaddition reaction with in situ generation of N-carbamoyl nitrones is presented. For the first time, N-Boc- and N-Cbz-protected isoxazolidines have been directly obtained as single diastereoisomers in generally high yields and enantiomeric excesses using mild reaction conditions and inexpensive, readily available Cinchona alkaloid quaternary ammonium salts as catalysts. Synthetic manipulations of the products provided highly valuable building blocks such as free isoxazolidines, a N-Boc-1,3-aminoalcohol, and a free delta-lactam. This report represents a pioneering work in the use of N-carbamoyl nitrones as electron-poor 1,3-dipoles and glutaconates as new dipolarophiles in asymmetric catalysis.
Subject(s)
Nitrogen Oxides/chemistry , Organic Chemicals/chemistry , Catalysis , Stereoisomerism , Sulfones/chemistrySubject(s)
Indoles/chemistry , Vinyl Compounds/chemistry , Catalysis , Cyclization , Molecular StructureABSTRACT
The unprecedented use of phase-transfer catalysis (PTC) in an asymmetric hydrophosphonylation reaction allows the obtainment of a range of optically active alpha-amino phosphonic acid derivatives directly from alpha-amido sulfones.
Subject(s)
Organophosphonates/chemical synthesis , Sulfones/chemistry , Catalysis , Imines/chemistry , Molecular Structure , Organophosphonates/chemistry , Phase Transition , StereoisomerismABSTRACT
A series of novel N,O-psiconucleosides has been prepared in both enantiomeric forms by resolution of an advanced racemic synthetic intermediate using (R)-N-phenylpantolactam as a chiral resolution agent. The absolute configuration of all of these compounds has been unequivocally established by chemical correlation with the novel (R)- or (S)-1-methyl-5-phenylpyrrolidine-2,3-dione, prepared from the known (R)- and (S)-1-methyl-5-phenylpyrrolidin-2-one, respectively.
Subject(s)
4-Butyrolactone/analogs & derivatives , Antiviral Agents/pharmacology , DNA Viruses/drug effects , Lactams/chemistry , RNA Viruses/drug effects , 4-Butyrolactone/chemistry , Animals , Antiviral Agents/chemical synthesis , DNA Viruses/growth & development , Esterification , Humans , Magnetic Resonance Spectroscopy , Pyrrolidines/chemistry , RNA Viruses/growth & development , Stereoisomerism , X-Ray DiffractionABSTRACT
Different malonates and beta-ketoesters can react with N-tert-butoxycarbonyl- (N-Boc) and N-benzyloxycarbonyl- (N-Cbz) protected alpha-amido sulfones in an organocatalytic asymmetric Mannich-type reaction. The reaction makes use of a simple and easily obtained phase-transfer catalyst and proceeds under very mild and user-friendly conditions. The optimised protocol avoids the preparation and the isolation of the relatively unstable N-Boc and N-Cbz imines that are generated in situ from the bench-stable alpha-amido sulfones. The corresponding Mannich bases are generally obtained in good yields and enantioselectivities, and can be readily transformed into key compounds, such as optically active beta3-amino acids in one easy step. Enantioenriched N-Boc and N-Cbz protected beta-amino acids that are suitable for peptide synthesis are also available from the Mannich adducts through simple manipulations. Control experiments showed the dual role of the enolate-catalyst ion pair in this reaction, as well as the crucial role of the presence of water to achieve high enantioselectivities.
ABSTRACT
Monodisperse and stable cobalt ferrite (CoFe2O4) nanoparticles (5.4 nm) have been produced, coated with mono- and difunctional phosphonic and hydroxamic acids, and fully characterized (using thermogravimetric analysis (TGA), dynamic light scattering (DLS), IR spectroscopy, transmission electron microscopy (TEM), and superconducting quantum interference device (SQUID) measurements). Cobalt leakage of the coated nanoparticles has been also studied. Magnetic measurements show the possible applications in hyperthermia at low frequencies, and for this reason, water-soluble coated CoFe2O4 can be seen as a first step toward the obtainment of novel systems for biomagnetic applications.
Subject(s)
Coated Materials, Biocompatible/chemistry , Cobalt/chemistry , Drug Carriers/chemistry , Ferric Compounds/chemistry , Nanoparticles/chemistry , Hydroxamic Acids/chemistry , Magnetics , Microscopy, Electron, Transmission , Nanoparticles/ultrastructure , Organophosphonates/chemistryABSTRACT
A study into the use of a chiral phase-transfer catalyst in conjunction with acetone cyanohydrin to effect the enantioselective formation of alpha-amino nitriles from alpha-amido sulfones is described. This novel catalytic asymmetric Strecker reaction is analyzed with regard to the possible mechanistic basis.
Subject(s)
Nitriles/chemical synthesis , Sulfones/chemistry , Carbonates/chemistry , Catalysis , Molecular Structure , Nitriles/chemistry , Phase Transition , Potassium/chemistry , Stereoisomerism , Water/chemistryABSTRACT
A simple and efficient organocatalytic enantioselective hydrophosphonylation of imines to enantiomerically enriched alpha-amino phosphonates is reported. By using 10 mol % of quinine as the catalyst in the enantioselective addition of diethyl phosphite to N-Boc protected imines, alpha-amino phosphonates are obtained in moderate to good yields and with up to 94% ee.
ABSTRACT
A straightforward synthetic protocol apt to synthesize a library constituted by all conduritol stereoisomers in solution phase is described and successfully applied to some polymer-supported substrates. During the solid-phase sequence, an unprecedented rearrangement of a resin-bound sulfone performed under the Ramberg-Bäcklund conditions appears of particular interest. Upon treatment with Me(3)Si-I, thiepanes supported on resin are found to undergo regio- and stereospecific ring contraction to a six-membered ring system with traceless cleavage from the solid support.