The synthesis of fluorinated aminophosphonic acid inhibitors of alanine racemase

✍ Scribed by Gary A. Flynn; Douglas W. Beight; Ekkehard H.W. Bohme; Brian W. Metcalf

• Book ID: 104233240
• Publisher: Elsevier Science
• Year: 1985
• Tongue: French
• Weight: 235 KB
• Volume: 26
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)80798-x

✦ Synopsis

The synthesis of 6-trifluoro, 8-difluoro, and B-monofluoro-1-aminoethanephosphonic acids is described utilizing fluorinated acetic acids as ,tarting materials. The inhibition of peptidoglycan biosynthesis continues to be a primary focus of antibacterial drug design. The intrinsic property of bacteria to incorporate D-alanine into their cell wall has prompted recent efforts to inhibit the essential pyridoxal dependent racemase responsible for the production of D-alanine. Cycloserine"' 0-carbamoyIserine2y3 and the B-haloalaninesZy4 1 are mechanism-based inactivators of bacterial alanine racemase whose presumed mechanism of action5 is illustrated in Scheme I. In contrast, L-l-aminoethanephosphonic acid 2. is a potent selective competitive inhibitor of alanine racemase in vitro which -when converted to the L-alanine dipeptide 5 (Alaphosphin) displays significant antibacterial _properties and synergism with D-cycloserine and 8-lactam antibiotics.6y' p"-Tkf po+yfy qp..cH H 3 H2N0 0 Lys CO,,