191226-90-1

Upstream product

• 143601-45-0 (S)-tert-butyl 4-<(benzyloxycarbonyl)amino>-3-oxo-5-phenylpentanoate 
• 540-88-5 acetic acid tert-butyl ester 
• 501-53-1 benzyl chloroformate 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 35909-92-3 N-carbobenzoxy-L-phenylalanine methyl ester 

Downstream Products

• 198020-19-8 (2R,2S)-(3S)-1,2-epoxy-3-phenylmethoxycarbonylamino-4-phenylbutane 
• 160232-13-3 (2R,3S)-3-N-((S)-tetrahydrofuran-3-yloxycarbonylamino)-2-hydroxy-1-N-(isobutyl)amino-4-phenylbutane 
• 160232-69-9 (2S,3S)-1-chloro-2-hydroxy-3-N-((S)-tetrahydrofuran-3-yloxycarbonylamino)-4-phenylbutane 
• 183255-96-1 (2R,3S)-1-chloro-2-hydroxy-3-N-benzyloxycarbonylamino-4-phenylbutane 
• 128018-43-9 N-benzyloxycarbonyl-3(S)-amino-1-chloro-4-phenyl-2(S)-butanol 
• 26049-94-5 (S)-benzyl (4-chloro-3-oxo-1-phenylbutan-2-yl)carbamate 

Relevant academic research and scientific papers

New approaches to the industrial synthesis of HIV protease inhibitors

Efficient and industrially applicable synthetic processes for precursors of HIV protease inhibitors (Amprenavir, Fosamprenavir) are described. These involve a novel and economical method for the preparation of a key intermediate, (3S)-hydroxytetrahydrofuran, from L-malic acid. Three new approaches to the assembly of Amprenavir are also discussed. Of these, a synthetic route in which an (S)-tetrahydrofuranyloxy carbonyl is attached to L-phenylalanine appears to be the most promising manufacturing process, in that it offers satisfactory stereoselectivity in fewer steps.

Synthesis of optically active α-aminoalkyl α′-halomethyl ketone: A cross-claisen condensation approach

(Equation presented) A simple and versatile method was developed for the synthesis of α-aminoalkyl α′-halomethyl ketone derivatives, which are useful intermediates of protease inhibitors. It involves selective halogenation of the α-position on a β-ketoester, which is prepared by cross-Claisen condensation using N-protected amino acid ester. The title compound is obtained in high yield after decarboxylation of the α-halo-β-ketoester.

Process for producing 3-amino-2-oxo-1-halogenopropane derivatives

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.