- Asymmetric Total Synthesis and Stereochemical Elucidation of the Antitumor Agent PM-94128
-
(Equation presented) PM-94128, a novel depsipeptide antitumor agent, has been synthesized for the first time through a highly stereocontrolled route. The key steps for the synthesis of the dihydroxyamino acid moiety involve a diastereoselective addition of tert-butyl lithiopropiolate to a chiral nitrone and a 2,3-dihydro[1,2]oxazin-6-one dihydroxylation. The synthesis serves to define the relative as well as the absolute configuration of the natural product (bearing five stereogenic centers).
- Patel, Samir K.,Murat, Karine,Py, Sandrine,Vallee, Yannick
-
p. 4081 - 4084
(2007/10/03)
-
- Macrocyclic difluorostatone derivatives useful as antiviral agents
-
The present invention provides novel macrocyclic difluorostatone derivatives which are useful as antiviral agents. More specifically, these novel compounds are useful as inhibitors of retroviral proteases required for replication, particularly the HIV-1 and HIV-2 viral proteases, in the prevention or treatment of infection by the human immunodeficiency virus (HIV), and in the treatment of consequent pathological conditions such as the acquired immunodeficiency syndrome (AIDS) in mammals capable of being infected with HIV virus.
- -
-
-
- Difluoro statone antiviral analogs
-
The present invention relates to difluorostatone derivatives useful as antiviral agents.
- -
-
-
- Probing enzyme stereospecificity. Inhibition of α-chymotrypsin and subtilisin Carlsberg by chiral amine- and aminoalcohol-derivatives
-
Various enantiomeric amine and aminoalcohol amide and α-ketoamide derivatives have been evaluated as competitive inhibitors of the representative serine proteases α-chymotrypsin (CT) and subtilisin Carlsberg (SC). Each compound studied was an effective competitive inhibitor of both enzymes. However, only for the best inhibitor, N-pyruvoyl-1-(1-naphthyl)ethylamine (K1 27 μM for the S-enantiomer with CT), was noteworthy enantiomeric discrimination manifest, with the S-enantiomer being a significantly more powerful inhibitor of CT and SC than its R-counterpart by factors of 12.6- and 73-fold, respectively. The enzyme-inhibitor interactions responsible for this strong binding and enantiomeric discrimination were revealed by molecular modelling analyses.
- Occhiato, Ernesto,Jones, J. Bryan
-
p. 4199 - 4214
(2007/10/03)
-