- A General, Catalytic, and Enantioselective Synthesis of (S)-γ-[(S)-1-Aminoalkyl]-γ-lactones
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A catalytic asymmetric synthesis of N-phthaloyl (S)-γ-[(S)-1-aminoalkyl]-γ-lactones, widely used intermediates in the preparation of hydroxyethylene dipeptide isosteres, is described. The highly enantiopure epoxy alcohols arising from the Sharpless epoxid
- Aguilar, Núria,Moyano, Albert,Pericàs, Miquel A.,Riera, Antoni
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p. 3560 - 3567
(2007/10/03)
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- Synthesis of the HIV-proteinase inhibitor Saquinavir: A challenge for process research
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The task of process research, namely developing efficient, economically and technically as well as ecologically feasible syntheses in time, is demonstrated on the HIV-proteinase inhibitor Saquinavir (1), a complex molecule comprising six stereo-centres. Based on the first 26-step research synthesis furnishing a 10% overall yield, process research established a new, short 11-step synthesis affording a 50% overall yield.
- Goehring, Wolfgang,Gokhale, Surendra,Hilpert, Hans,Roessler, Felix,Schlageter, Markus,Vogt, Peter
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p. 532 - 537
(2007/10/03)
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- Alcohols
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Novel alcohols of the formula STR1 wherein Ra is azido or phthalimido, R4 is alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl, R7 and R8 together are a trimethylene or tetramethylene group which is optionally substituted by hydroxy, alkoxycarbonylamino or acylamino or in which one --CH2 -- group is replaced by --NH--, --N(alkoxycarbonyl)-, --N(acyl)- or --S-- or which carries a fused cycloalkane, aromatic or heteroaromatic ring, and R9 is alkoxycarbonyl, monoalkylcarbamoyl, monoaralkylcarbamoyl, monoarylcarbamoyl or a group of the formula STR2 in which R10 and R11 each is alkyl, are described along with a process for their manufacture. These alcohols are useful as intermediates, for example in the manufacture of amino acid derivatives having antiviral activity.
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- Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959
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Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials.Six approaches for the large-scale synthesis of this compound have been studied.All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5.They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation.The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1.Kilogram quantities of Ro 31-8959 have been prepared using this route.
- Parkes, Kevin E. B.,Bushnell, David J.,Crackett, Peter H.,Dunsdon, Stephen J.,Freeman, Andrew C.,et al.
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p. 3656 - 3664
(2007/10/02)
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