Dinesh Gala

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.

Mono N-arylation of piperazine(III): metal-catalyzed N-arylation and its application to the novel preparations of the antifungal posaconazole and its advanced intermediate

Abstract A novel application of Pd 0 -catalyzed arylation to mono N -arylated piperazines, its mechanism, and its application towards the novel syntheses of the key differentially N , N ′-diarylated piperazine antifungal intermediate N -(4-hydroxyphenyl)- N′ -(4-aminophenyl)piperazine 5 as well as posaconazole 1 are described.

Sequential mono-N-arylation of piperazine nitrogens. Part 1: A simplified method and its application to the preparation of a key N,N′-biaryl piperazine antifungal intermediate

Abstract A simple sequential N-arylation of piperazine without the use of a protecting group, catalyst, specialized equipment or a large excess of piperazine, and its application towards the preparation of the key differentially N,N′-biarylated piperazine antifungal intermediate N-(4-hydroxyphenyl)-N′-(4-aminophenyl)piperazine, 6, is 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.

Reaction of aziridinium ions with organometallic reagents: optimization of the key step of ecopipam synthesis

Formation, stability and reactivity of aziridinium ions 3 towards organometallic reagents was explored and optimized for the efficient preparation of key drug intermediate 5c.

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.

Guanine hydrolysis under basic conditions to substituted imidazoles

Abstract First base induced opening of multicyclic guanines to isolable substituted imidazoles, and possible mechanism for this observation are described.