174152-18-2

Upstream product

• 935-79-5 cis-1,2,3,6-tetrahydrophthalic anhydride 
• 439919-46-7 cis-1,6-dihydroxymethyl-3-cyclohexene 
• 98516-11-1 acetic acid (1S,6R)-6-hydroxymethyl-cyclohex-3-enylmethyl ester 

Downstream Products

• 174152-14-8 Acetic acid (1S,2R)-2-(diethoxy-phosphorylmethyl)-cyclohexylmethyl ester 
• 174152-17-1 Acetic acid (1S,6R)-6-(diethoxy-phosphorylmethyl)-cyclohex-3-enylmethyl ester 

Relevant academic research and scientific papers

TRICYCLIC P2-LIGAND CONTAINING POTENT HIV-PROTEASE INHIBITORS

Compounds of formula (I), pharmaceutical compositions comprising compounds of the formula (I), and methods of treating an HIV infection comprising administering an effective amount of one or more compounds of formula (I), or a pharmaceutical composition comprising same.

Structure-Based Design of Highly Potent HIV-1 Protease Inhibitors Containing New Tricyclic Ring P2-Ligands: Design, Synthesis, Biological, and X-ray Structural Studies

We describe here design, synthesis, and biological evaluation of a series of highly potent HIV-1 protease inhibitors containing stereochemically defined and unprecedented tricyclic furanofuran derivatives as P2 ligands in combination with a variety of sulfonamide derivatives as P2′ ligands. These inhibitors were designed to enhance the ligand-backbone binding and van der Waals interactions in the protease active site. A number of inhibitors containing the new P2 ligand, an aminobenzothiazole as the P2′ ligand and a difluorophenylmethyl as the P1 ligand, displayed very potent enzyme inhibitory potency and also showed excellent antiviral activity against a panel of highly multidrug-resistant HIV-1 variants. The tricyclic P2 ligand has been synthesized efficiently in an optically active form using enzymatic desymmetrization of meso-1,2-(dihydroxymethyl)cyclohex-4-ene as the key step. We determined high-resolution X-ray structures of inhibitor-bound HIV-1 protease. These structures revealed extensive interactions with the backbone atoms of HIV-1 protease and provided molecular insights into the binding properties of these new inhibitors.

Lipase-catalyzed kinetic resolution of cis-1-diethylphosphonomethyl-2-hydroxymethylcyclohexane. Application to enantioselective synthesis of 1-diethylphosphonomethyl-2-(5'-hydantoinyl)cyclohexane

A kinetic resolution of cis-1-diethylphosphonomethyl-2-hydroxymethylcyclohexane 1 by lipase has been developed. The transesterification of (±)-1 with vinyl acetate in the presence of Lipase AK without solvent proceeded to give (+)-1 and the corresponding acetate (+)-5 in good yield and high enantiomeric ratio. The alcohol (+)-1 was transformed to the optically active hydantoins 12 and 13, possible intermediates for the synthesis of conformational constrained analogues of AP-5.