111138-83-1Relevant articles and documents
An Efficient Stereocontrolled Strategy for the Synthesis of Hydroxyethylene Dipeptide Isosteres
Stuk, Timothy L.,Haight, Anthony R.,Scarpetti, David,Allen, Michael S.,Menzia, Jerome A.,et al.
, p. 4040 - 4041 (1994)
A novel and practical synthesis of hydroxyethylene dipeptide isostere 9 from L-phenylalanine via the formation and stereospecific reduction of an enaminone is described.
Structural Analysis of Potent Hybrid HIV-1 Protease Inhibitors Containing Bis-tetrahydrofuran in a Pseudosymmetric Dipeptide Isostere
Rusere, Linah N.,Lockbaum, Gordon J.,Henes, Mina,Lee, Sook-Kyung,Spielvogel, Ean,Rao, Desaboini Nageswara,Kosovrasti, Klajdi,Nalivaika, Ellen A.,Swanstrom, Ronald,Kurt Yilmaz, Nese,Schiffer, Celia A.,Ali, Akbar
supporting information, p. 8296 - 8313 (2020/09/22)
The design, synthesis, and X-ray structural analysis of hybrid HIV-1 protease inhibitors (PIs) containing bis-tetrahydrofuran (bis-THF) in a pseudo-C2-symmetric dipeptide isostere are described. A series of PIs were synthesized by incorporating bis-THF of darunavir on either side of the Phe-Phe isostere of lopinavir in combination with hydrophobic amino acids on the opposite P2/P2′ position. Structure-activity relationship studies indicated that the bis-THF moiety can be attached at either the P2 or P2′ position without significantly affecting potency. However, the group on the opposite P2/P2′ position had a dramatic effect on potency depending on the size and shape of the side chain. Cocrystal structures of inhibitors with wild-type HIV-1 protease revealed that the bis-THF moiety retained similar interactions as observed in the darunavir-protease complex regardless of the position on the Phe-Phe isostere. Analyses of cocrystal structures and molecular dynamics simulations provide insights into optimizing HIV-1 PIs containing bis-THF in non-sulfonamide dipeptide isosteres.
A (2 R, 3 S) - 1 - chloro - 3 - tert-butoxy amide - 4 - phenyl - 2 - butanol preparation method
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Paragraph 0035; 0040; 0056; 0072-0074, (2017/09/26)
The invention provides a preparation method for (2R,3S)-1-chlorine-3-tert-butoxycarbonylamino-4-phenyl-2-butanol. The preparation method comprises the steps that L-phenylalanine is taken as raw materials, protected by adopting benzyl, esterified and then catalyzed through NMM to generate a mixed anhydride compound, the mixed anhydride compound reacts with diazomethane to generate diazoketone, a reduction reaction and palladium carbon reduction are performed, and finally the intermediate (2R,3S)-1-chlorine-3-tert-butoxycarbonylamino-4-phenyl-2-butanol is obtained. According to the preparation method, the low-cost benzyl is adopted to protect amidogen, the synthetic route is reasonable, the operation technology is simple, safe and high in yield, industrialization can be well achieved, and the production efficiency is improved.
