98516-10-0Relevant academic research and scientific papers
TRICYCLIC P2-LIGAND CONTAINING POTENT HIV-PROTEASE INHIBITORS
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, (2021/09/26)
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
Ghosh, Arun K.,Kovela, Satish,Osswald, Heather L.,Amano, Masayuki,Aoki, Manabu,Agniswamy, Johnson,Wang, Yuan-Fang,Weber, Irene T.,Mitsuya, Hiroaki
, p. 4867 - 4879 (2020/05/13)
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.
An enantioselective enzymatic desymmetrization route to hexahydro-4H-furopyranol, a high-affinity ligand for HIV-1 protease inhibitors
Ghosh, Arun K.,Sarkar, Anindya
supporting information, p. 3230 - 3233 (2017/07/27)
An enantioselective synthesis of (3aS,4S,7aR)-hexahydro-4H-furo[2,3-b]pyran-4-ol, a high-affinity nonpeptide ligand for a variety of potent HIV-1 protease inhibitors is described. The key steps involved a highly enantioselective enzymatic desymmetrization
Enantioselective Syntheses of (–)-Alloyohimbane and (–)-Yohimbane by an Efficient Enzymatic Desymmetrization Process
Ghosh, Arun K.,Sarkar, Anindya
, p. 6001 - 6009 (2016/12/26)
Enantioselective syntheses of (–)-alloyohimbane and (–)-yohimbane were accomplished in a convergent manner. The key step involves a modified mild protocol for the enantioselective enzymatic desymmetrization of a meso-diacetate. This provides convenient access to an optically active monoacetate in multi-gram quantities and in high enantiomeric purity. This monoacetate was converted to (–)-alloyohimbane. Reductive amination of the derived aldehyde caused isomerization to the trans-product and, ultimately, the formation of (–)-yohimbane.
Access to the akuammiline family of alkaloids: Total synthesis of (+)-scholarisine A
Adams, Gregory L.,Carroll, Patrick J.,Smith, Amos B.
, p. 519 - 528 (2013/02/25)
The planning and implementation of an enantioselective total synthesis of (+)-scholarisine A is presented. Key tactics employed include a novel cyclization, consisting of a nitrile reduction coupled with concomitant addition of the resultant amine to an epoxide; a modified Fischer indolization; an oxidative lactonization of a diol in the presence of an indole ring; and a late-stage cyclization to complete the caged ring scaffold. The development of a possible "retro-biosynthetic" approach to other members of the akuammiline alkaloid family is also described.
Total synthesis of (+)-scholarisine A
Adams, Gregory L.,Carroll, Patrick J.,Smith III, Amos B.
, p. 4037 - 4040 (2012/04/10)
An effective total synthesis and assignment of the absolute configuration of the architecturally challenging compound (+)-scholarisine A has been achieved via a 20-step sequence. Highlights include a reductive cyclization involving a nitrile and an epoxide, a modified Fischer indole protocol, a late-stage oxidative lactonization, and an intramolecular cyclization leading to the indolenine ring system of (+)-scholarisine A.
The first synthesis of the ABC-ring system of 'upenamide
Schmidt, Jan Peter,Beltran-Rodil, Sandra,Cox, Rhona J.,McAllister, Graeme D.,Reid, Mark,Taylor, Richard J. K.
, p. 4041 - 4044 (2008/02/11)
The first synthetic route to the spirooxaquinolizidinone core (ABC core) of the macrocyclic marine alkaloid 'upenamide (1) has been developed. All five stereocenters were introduced with complete stereocontrol. The hydroxyl group at C-11 was introduced by a regio- and stereoselective SeO2-mediated allylic oxidation. The spirocyclic skeleton was formed by a stannous chloride induced deacetalization-bicyclization procedure. Further stereocenters were introduced by an enzymatic desymmetrization and by incorporation of an (S)-malic acid derived building block.
Selective mono-acylation of meso- and C2-symmetric 1,3- and 1,4-diols
Clarke, Paul A.
, p. 4761 - 4763 (2007/10/03)
The direct one-pot mono-acylation of meso and C2-symmetric 1,3- and 1,4-diols has been achieved using carboxylic acid anhydrides and catalytic amounts of cerium trichloride.
Resolution and stereoselective synthesis of the herpes thymidine kinase inhibitor L-653180
Von Langen, Derek J.,Tolman
, p. 677 - 681 (2007/10/03)
Resolution of L-653180, (±)-9-{[(Z)-2-(hydroxymethyl)cyclohexyl]-methyl}guanine, a racemic, nonsubstrate inhibitor of HSV-TK, was achieved and the absolute stereochemistry of the enantiomers was determined. Enzyme inhibition was shown to reside in the ena
