Background: Phosphonates derivatives are in the area of interests because of their unique chemical-physical features. These compounds manifest variety of biological interactions within the sensitive living cells, including impact on particular enzymes activities. Biological “cause and effect” interactions are based upon the specific matching between the structures and/or compounds and this is usually the result of proper optical configurations of particular chiral moieties. Presented research is targeted to the phosphonates with the heteroatom incorporated in their side functionalities. Such molecules are described as possible substrates of bioconversion for the first time lately and this field is not fully explored. Results: Presented research is targeted to the synthesis of pure hetero-phosphonates enantiomers. The catalytic activity of yeasts and moulds were tested towards two substrates: the thienyl and imidazole phosphonates to resolve their racemic mixtures. Biotransformations conditions differed depending on the outcome, what included changing of following parameters: type of cultivation media, bioprocess duration (24–72 h), additional biocatalyst pre-treatment (24–48 h starvation step triggering the secondary metabolism). (S)-1-amino-1-(3-thienyl)methylphosphonate was produced with the assistance of R. mucilaginosa or A. niger (e.e. up to 98% and yield up to 100%), starting from the 3 mM of substrate racemic mixture. Bioconversion of racemic mixture of 3 mM of (1-amino-1-(4-imidazole)methylphosphonic acid) resulted in the synthesis of S-isomer (up to 95% of e.e.; 100% of yield) with assistance of R. mucilaginosa. 24 h biotransformation was conducted with biomass preincubated under 48-hour starvation conditions. Such stereoselective resolution of the racemic mixtures of substrates undergoes under kinetic control with the conversion of one from the enantiomers. Conclusions: Composition of the culturing media and pre-incubation in conditions of nutrient deficiency were significant factors influencing the results of kinetic resolution of racemic mixtures of phosphonic substrates and influencing the economic side of the biocatalysis e.g. by determining the duration of whole biocatalytic process. Graphical

A wide spectrum of commercially available lipases and microbial whole cells catalysts were tested for biotransformations of 2-hydroxy-2-(ethoxyphenylphosphinyl)acetic acid 1 ( Fig. 2 ) and its bytyryl ester. The best results were achieved for biocatalytic hydrolysis of ester: 2-butyryloxy-2-(ethoxyphenylphosphinyl)acetic acid 2 ( Fig. 2 ) performed by lipase from Candida cylindracea, what gave optically active products with 85% enantiomeric excess, 50% conversion degree and enantioselectivity 32.9 for one pair of enantiomers. Also enzymatic systems of Penicillium minioluteum and Fusarium oxysporum were able to hydrolyze tested compound with high enantiomeric excess (68-93% ee), enantioselectivity (44 for one pair of enantiomers) and conversion degree about 50-55%. Enzymatic acylation of hydroxyphosphinate was successful in case when porcine pancreas lipase was used. After 4 days of biotransformation the conversion reaches 45% but the enantiomeric enrichment of the isomers mixture do not exceed 43%. Obtained chiral compounds are valuable derivatizing agents for spectroscopic (NMR) evaluation of enantiomeric excess for particular compounds (e.g. amino acids).

Phosphonates derivatives are compounds of interests and are applied as drugs of, e.g., antibacterial antiviral activities, connected with their inhibitory activity towards different enzymes, which is related to the configuration of particular compound isomers. The biological synthesis of such molecules is the method of choice and can be carried out using enzymes or whole cells from organisms. Photobiocatalysts employed in the bioconversion of epoxymethyl dimethyl phosphonate are able to convert this substrate into a pure geometric isomer of the unsaturated product, dimethyl (1E)-3-hydroxyprop-1-enylphosphonate, which is a rare and expensive compound of high added value. Six different strains were screened towards dimethyl epoxy phosphonate and in the case of Synechococcus bigranulatus, over 99% conversion was achieved. The product structure was confirmed with Mass Spectroscopy (MS); ¹H, ¹³C, ³¹P, and 2D Nuclear Magnetic Resonance (NMR); and Infrared Spectroscopy (IR).

Phosphonates derivatives are compounds of interests and are applied as drugs of e.g. antibacterial antiviral activities, what is connected with their inhibitory activity towards different enzymes, what in turn is in the relation to the configuration of particular compounds izomers. Biological synthesis of such molecules is the method of choice and can be carried on with enzymes or whole cells of organisms. Photobiocatalysts employed in bioconversion of epoxy dimethyl phosphonate are able to convert this substrate into geometric isomers of the unsaturated product, which is classified as very rare and expensive compound of high added value. Six different strains were screened towards dimethyl epoxy phosphonate and in case of Synechococcus bigranulatus 99% of conversion degree was achieved. Product structure and yield of the reaction were confirmed with Mass Spectroscopy (MS); Nuclear Magnetic Resonance (NMR) of isotopes 1H, 13C, and 31P, 2D NMR; and Infrared Spectroscopy (IR).