Donald J. DiBenedetto

Preparations of antifungal Sch 42427/SM 9164: Preparative chromatographic resolution, and total asymmetric synthesis via enzymatic preparation of chiral α-hydroxy arylketones

Abstract Efficient approaches towards the preparation of chiral azole antifungals Sch 42427/SM 9164 (1) via large scale chromatographic separation of its enantiomers, or via enzymatic syntheses of key chiral intermediates α-hydroxy arylketones 5 in excellent enantiomeric excesses (ees) are described.

Total chiral synthesis of azole antifungals via α-hydroxylation of ketones

The use of camphorsulfonyl oxaziridines for the preparation of 2′,4′-difluoro-(R)-2-hydroxypropiophenone, (2), a key intermediate for the synthesis of azole antifungals Sch 42427 and ER-30346 (1) in excellent enantiomeric excess and high chemical yield is described.

A convenient, improved synthesis of (camphoryl)sulfonyl oxaziridines

Abstract A convenient, efficient procedure for the large scale synthesis of chiral oxidizing reagents (+), and (−)-((8,8-dichlorocamphoryl)sulfonyl)oxaziridine, 5, as well as of 8,8 unsbustituted (+), and (−) (camphoryl)sulfonyl oxaziridine, 4, from (+), or (−) (camphorylsulfonyl)imine, 2, in step yields of 83% to 95%, is reported.

A rational approach to chiral α-hydroxy aryl ketones from chiral aryl epoxides via regioselective, stereo retentive oxidative epoxide opening: Its application to the synthesis of antifungal Sch 42427/SM 9164

Abstract A new, mild method for the direct conversion of chiral aryl epoxides to hydroxy-protected chiral α-hydroxy aryl ketones with complete retention of the chiral center and good regioselectivity has been established. An application of this new reaction to the synthesis of antifungal Sch 42427/SM 9164 is also described.

A novel synthesis of guanine PDE inhibitors via tricyclic imidazopyrimidines

A new method for the preparation of developmental tetracyclic guanine PDE inhibitors via a common tricyclic pyrimidine intermediate is described.

Pyrimidine to guanine PDE inhibitors: determination of chemical course via structure elucidation

Structure elucidation of several new pyrimidines containing a varying extent of hydrogen bonding allowed for determination of the course of chemical reactions towards the preparation of novel substituted pyrimidines.

Metal salts induced improved α-hydroxylation of ketones for the preparation of the key chiral intermediate of azole antifungals

Abstract The first example demonstrating the influence of metal salts for an improved synthesis of 2′,4′-difluoro-( R )-2-hydroxypropiophenone, ( 2 ) a key intermediate for the preparation of azole antifungals such as Sch 42427 ( 1 ) in excellent enantiomeric excess and high chemical yield via the use of camphorsulfonyloxaziridines is described.