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Design and synthesis of the novel antibacterials 3-fluoro-D-alanine (FA) as well as its 2-deuterated version (DFA) are described. The design of FA exploits a fundamental divergence in biosynthesis of the peptidoglycan component of the bacterial cell wall and of the metabolic pathways in humans. This divergence suggested application of the concept of antimetabolite synthesis via the specific approach of photofluorination. Thus, photofluorination of a key component of the bacterial cell wall (D-alanine) generated FA. FA in fact displays a high degree of wide-spectrum antibacterial activity. A variant of FA with increased metabolic stability-and with unimpaired antibacterial activity-was obtained via photofluorination of 2-deuterio-D-alanine, namely 3-fluoro-D-alanine-2-d (DFA). (DFA is the unorthodox component of a novel, fixed-ratio antimicrobial combination, effective in vitro and in vivo against every bacterial strain tested.)Notwithstanding the importance of organic fluorine compounds, their synthesis by direct (substitutive) fluorination is seldom practicable. To fill this gap, we have proposed an approach named photofluorination, which represents the first general and selective method for substitutive fluorination of organic compounds.la Application of this method for C-fluorination of the amino acids D-and L-alanine as well as of 2-deuterio-D-alanine is presented now. These syntheses also illustrate the utility of photofluorination for generation of antimetabolites via fluorination of selected metabolites.IbElectrophilic fluorination of olefins as well as of activated aromatics by fluoroxytrifluoromethane (CF30F) was first described by Porter and Cady.2 The full potential and wide applicability of electrophilic fluorination by CF3OF were recognized and demonstrated by

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