ABSTRACT
The first total synthesis of aeruginosin 98B was accomplished. The key step is a highly diastereoselective Pd-catalyzed intramolecular asymmetric allylic alkylation reaction of a diastereomeric mixture of allylic carbonates that is enabled by the use of racemic phosphine ligand L1.
Subject(s)
Oligopeptides/chemical synthesis , Alkylation , Catalysis , Palladium/chemistryABSTRACT
The discovery of novel and highly potent oxopiperazine based B1 receptor antagonists is described. Compared to the previously described arylsulfonylated (R)-3-amino-3-phenylpropionic acid series, the current compounds showed improved in vitro potency and metabolic stability. Compound 17, 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide, showed EC(50) of 10.3 nM in a rabbit biochemical challenge model. The practical syntheses of chiral arylsulfonylated oxopiperazine acetic acids are also described.
Subject(s)
Acetamides/therapeutic use , Bradykinin B1 Receptor Antagonists , Inflammation/drug therapy , Pain/drug therapy , Piperazines/therapeutic use , Acetamides/chemical synthesis , Acetamides/chemistry , Animals , Dogs , Inhibitory Concentration 50 , Mice , Models, Animal , Molecular Structure , Piperazines/chemical synthesis , Piperazines/chemistry , Rabbits , Rats , Receptor, Bradykinin B1/chemistry , Stereoisomerism , Structure-Activity RelationshipABSTRACT
A variety of N-tert-butanesulfinyl imines were reduced with NaBH4 in THF containing 2% water to provide the corresponding secondary sulfinamides in high yield and diastereoselectivity. By using the same sulfinyl imine starting materials and changing the reductant to L-Selectride, the stereoselectivity could be efficiently reversed to afford the opposite product diastereomer in high yield and selectivity.
Subject(s)
Imines/chemistry , Sulfonium Compounds/chemistry , Borohydrides/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , StereoisomerismABSTRACT
Tipranavir, an important antiviral agent in clinical development for the treatment of HIV, is synthesized in 15 linear steps from readily available starting materials in 25% overall yield by utilizing Pd- and Mo-catalyzed DYKAT reactions to control the quaternary and tertiary stereogenic centers, respectively.