Fluoroacetate natural product

Despite these great discoveries, for a long time fluorine chemistry remained more oriented toward the field of materials than toward medicinal chemistry. This can be explained by the fact that a traditional source of inspiration often comes from nature, and organofluorine compounds are almost absent as natural products. Moreover, the only one known at that time was fluoroacetic acid, a potent poison. 

Few of these have been found so far, the first not until 1944, in a poisonous South African plant, Gifblaar . The toxic principle of this was identified44 as fluoroacetic acid. A recent summary45 indicates that some 10 fluorinated natural products have now been isolated (in small amounts) largely from other plant sources, their formation being rationalized from the metabolism of fluoroacetate. The exception is nucleocidin (1), an antibiotic from a microbial source (Streptomyces calvus), originating in an Indian soil sample, and which has a ribose moiety carrying fluorine at C4. 

Murphy CD, Schaffrath C, O Hagan D (2003) Fluorinated Natural Products The Biosynthesis of Fluoroacetate and 4-Fluorothreonine in Streptomyces cattleya. Chemosphere 52 455... 

A method for the asymmetric hydrogenation of seven-membered cyclic imines of benzodiazepinones and benzodiazepines has recently been published. The chiral cyclic amines generated from these reactions make up the cores of many natural products and clinical drugs. Iridium-bisphosphine catalyst systems were investigated and found to give promising enantios-electivities which could be improved upon addition of morpholine tri-fluoroacetate. The optimum conditions, applied to model compound 50, are shown in Scheme 14.19, giving 51 in excellent enantioselectivity and complete conversion. 

Murphy, C.D., Schafifrath, C., and O Hagan, D. (2003) Fluorinated natural products the biosynthesis of fluoroacetate and 4-fluorofhreonine in Streptomyces cattleya. Chemosphere, 52, 455 161. 

Fluoroacetate. Fluoroacetate 1 is the most ubiquitous fluorine-containing natural product and has been identified in over 30 plants, principally species from Africa and Australia, and also as a secondary metabolite in the bacteria Streptomyces cattleya (see below). The compoimd was first identified by Marais (4) in South Africa as the toxic principle in plants of Dichapetalum cymosum (gifblaar). The young leaves of this plant are particularly toxic in the spring when levels of fluoroacetate of up to... 

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