Stereoselective synthesis of Xaaψ[CH₂CH(OH)]Yaa dipeptidomimetics and their inclusion in HIV‐1 protease inhibitors

Abstract

Two stereoselective syntheses of a new pseudodipeptide isostere, the right‐hand hydroxyethylene dipeptido‐mimetic (Xaaψ[CH2CH(OH)]Yaa), are presented. In one method readily available amino acids are used as starting materials for Evans chiral aldol condensation chemistry. The second method relies on the synthesis of an anti‐aldol product for the hydroxyethylene isostere via an E‐selective ethyl hydrocinnamate enolization, and thus allows for the synthesis of isosteres having side chains other than those available from amino acids. Both methods are illustrated by the chiral synthesis of Boc‐Pheψ[CH2CH(OH)]Phe. Two diastereomers, (S,S,R)and (S,R,R) are incorporated into an HIV‐1 protease inhibitor template which yields potent inhibitors of HIV‐1 protease when the pseudodipeptide isostere is Pheψ[CH(OH)CH2]Phe or Pheψ[CH(OH)CH(OH)]Phe. The resulting Pheψ[CH2CH(OH)]Phe‐containing inhibitors possess modest potency. © Munksgaard 1995.

Practical Asymmetric Synthesis of Sitagliptin Phosphate Monohydrate

“…The obtained solution was evaporated and purified over silica gel column chromatography (PE/EtOAc, 5:1) to give compound 8a as a white solid. 89% yield (93 mg); [α] D 22 +18.10 (c 1.0, CHCl 3 ); 1 H-NMR (400 MHz, CDCl3) δ 9.69 (s, 1H), 7.31–7.21 (m, 3H), 7.15 (d, J = 8.2 Hz, 2H), 4.75 (s, 1H), 4.25 (s, 1H), 2.95–2.90 (m, 1H), 2.79 (dd, J = 8.2 Hz, 12 Hz, 1H), 2.63–2.48 (m, 2H), 1.30 (s, 9H) [ 24 ].…”

One-pot preparation of phenylpropanoid esters co-catalyzed by boric acid and piperidine

“…Furthermore, hydrocinnamate is a key precursor of 1,3,4,9-tetrahydropyrano [3,4-b] indole-1-acetic acid, which is used as an analgesic, inflammation inhibitor, and antipyretic [9]. Hydrocinnamate has also been used for the synthesis of HIV-1 protease inhibitors [10]. P-methoxycinnamates are commercially popular UV-B screening compounds in sunscreen products [11].…”

Chitosan as biosupport for the MW-assisted synthesis of palladium catalysts and their use in the hydrogenation of ethyl cinnamate

“…As an example, EHC is used for the synthesis of the HIV-1 protease inhibitor and lastly it also finds several employments in food and flavor industries [33,34]. This reaction has been carried out by other researches under different reaction conditions [14,[35][36][37][38][39][40][41], including also microwave irradiation [38][39][40][41].…”