Martin Steinman

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.

Diastereoisomerism in 1,3,5-triazine through nitrogen substituents

Abstract The reaction of formaldehyde with ( d,l ) α-methylbenzylamine resulted in a mixture of products of which the desired 1,3,5 triazines 2a and 3a could not be isolated. On the other hand, the reaction of ( d,l ) 2,3 ( trans )-diphenylcyclopropanamine 1b with formaldehyde results in the formation of the diasteromeric nonsymmetrical 1,3,5-triazine 2b and the symmetrical 1,3,5-triazine 3b . These triazines were isolated and their structures were determined by NMR. The stereochemical outcome is discussed.

Novel, stereoselective syntheses of penem antibiotics: efficient, formal syntheses of SCH 34343

Abstract Novel, stereoselective syntheses of (3S, 4R, 5R)-1-(allyloxycarbonyl)methyl-3-[1-hydroxyethyl]-4-β-naphthoxy(thiocarbonyl)thio-2-azetidinone (13) and (3S, 4R, 5R, 3′S, 4′R, 5′R)-4,4′-dithio-bis-1-(allyloxy-carbonyl)methyl-3-[-1-hydroxyethyl]-2-azetidinone (22), key intermediates in the synthesis of the penem antibiotic Sch 34343, were developed starting from readily available 6-aminopenicillanic acid. Advantages of these routes include 1) the highly stereospecific introduction of the hydroxyethyl sidechain with the desired (R)-configuration and 2) the retention of the sulfur of the starting material.