- Merging lithium carbenoid homologation and enzymatic reduction: A combinative approach to the HIV-protease inhibitor Nelfinavir
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An effective stereocontrolled synthesis of the HIV protease inhibitor Nelfinavir is reported. Two transformations were identified crucial for achieving success: the formation of a densely functionalized α-chloroketone via the homologation of a Weinreb ami
- Castoldi, Laura,Ielo, Laura,Hoyos, Pilar,Hernáiz, María J.,De Luca, Laura,Alcántara, Andrés R.,Holzer, Wolfgang,Pace, Vittorio
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- Continuous flow synthesis of α-halo ketones: Essential building blocks of antiretroviral agents
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The development of a continuous flow process for the multistep synthesis of α-halo ketones starting from N-protected amino acids is described. The obtained α-halo ketones are chiral building blocks for the synthesis of HIV protease inhibitors, such as atazanavir and darunavir. The synthesis starts with the formation of a mixed anhydride in a first tubular reactor. The anhydride is subsequently combined with anhydrous diazomethane in a tube-in-tube reactor. The tube-in-tube reactor consists of an inner tube, made from a gas-permeable, hydrophobic material, enclosed in a thick-walled, impermeable outer tube. Diazomethane is generated in the inner tube in an aqueous medium, and anhydrous diazomethane subsequently diffuses through the permeable membrane into the outer chamber. The α-diazo ketone is produced from the mixed anhydride and diazomethane in the outer chamber, and the resulting diazo ketone is finally converted to the halo ketone with anhydrous ethereal hydrogen halide. This method eliminates the need to store, transport, or handle diazomethane and produces α-halo ketone building blocks in a multistep system without racemization in excellent yields. A fully continuous process allowed the synthesis of 1.84 g of α-chloro ketone from the respective N-protected amino acid within ~4.5 h (87% yield).
- Pinho, Vagner D.,Gutmann, Bernhard,Miranda, Leandro S. M.,De Souza, Rodrigo O. M. A.,Kappe, C. Oliver
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supporting information
p. 1555 - 1562
(2014/03/21)
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- Development of a continuous process for the industrial generation of diazomethane
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The development of a safe process for the industrial generation of diazomethane is described. Diazomethane is produced and consumed in a continuous process capable of generating between 50 and 60 tonnes per year whilst the maximum inventory is maintained
- Proctor, Lee D.,Warr, Antony J.
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p. 884 - 892
(2013/09/06)
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- Process for the reduction of carbonyl compounds
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PCT No. PCT/JP97/00189 Sec. 371 Date Dec. 29, 1997 Sec. 102(e) Date Dec. 29, 1997 PCT Filed Jan. 29, 1997 PCT Pub. No. WO97/28105 PCT Pub. Date Aug. 7, 1997The present invention provides a process for reducing carbonyl compounds to hydroxy compounds, in particular stereoselectively reducing alpha -aminohaloketone derivatives, under mild conditions in an easy and simple manner, which comprises reacting a carbonyl compound of the general formula (1) with an organoaluminum compound of the general formula (4) to provide the corresponding alcohol compound of the general formula (5).
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- HIV protease inhibitors
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HIV protease inhibitors, obtainable by chemical synthesis, inhibit or block the biological activity of the HIV protease enzyme, causing the replication of the HIV virus to terminate. These compounds, as well as pharmaceutical compositions that contain these compounds and optionally other anti-viral agents as active ingredients, are suitable for treating patients or hosts infected with the HIV virus, which is known to cause AIDS.
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- Process for producing 3-amino-2-oxo-1-halogenopropane derivatives
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Compounds formed by reacting a protected amino acid with an alkali metal enolate of an alkyl acetate are reacted with a halogenating agent for halogenation of the 2-position, or a protected amino acid is reacted with an alkali metal enolate of an alkyl halogenoacetate, to form a 4-amino-3-oxo-2-halogenobutanoic acid ester derivative, and hydrolysis and decarboxylation are conducted to produce a 3-amino-2-oxo-1-halogenopropane derivative or its salt. The present method is a useful process for producing a 3-amino-2-oxo-1-halogenopropane derivatives which can easily be converted to a 3-amino-1,2-epoxypropane.
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- Viracept (nelfinavir mesylate, AG1343): A potent, orally bioavailable inhibitor of HIV-1 protease
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Using a combination of iterative structure-based design and an analysis of oral pharmacokinetics and antiviral activity, AG1343 (Viracept, nelfinavir mesylate), a nonpeptidic inhibitor of HIV-1 protease, was identified. AG1343 is a potent enzyme inhibitor
- Kaldor, Stephen W.,Kalish, Vincent J.,Davies II, Jay F.,Shetty, Bhasker V.,Fritz, James E.,Appelt, Krzysztof,Burgess, Jeffrey A.,Campanale, Kristina M.,Chirgadze, Nickolay Y.,Clawson, David K.,Dressman, Bruce A.,Hatch, Steven D.,Khalil, Deborah A.,Kosa, Maha B.,Lubbehusen, Penny P.,Muesing, Mark A.,Patick, Amy K.,Reich, Siegfried H.,Su, Kenneth S.,Tatlock, John H.
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p. 3979 - 3985
(2007/10/03)
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- HIV protease inhibitors
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HIV protease inhibitors, obtainable by chemical synthesis, inhibit or block the biological activity of the HIV protease enzyme, causing the replication of the HIV virus to terminate. These compounds, as well as pharmaceutical compositions that contain the
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- HIV protease inhibitors
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HIV protease inhibitors, obtainable by chemical synthesis, inhibit or block the biological activity of the HIV protease enzyme, causing the replication of the HIV virus to terminate. These compounds, as well as pharmaceutical compositions that contain these compounds and optionally other anti-viral agents as active ingredients, are suitable for treating patients or hosts infected with the HIV virus, which is known to cause AIDS.
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- Intermediate and process for making
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The present invention provides novel HIV protease inhibitors, pharmaceutical formulations containing those compounds and methods of treating and/or preventing HIV infection and/or AIDS.
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