- Synthesis of 5,6,7,8-Tetrahdro-D-neopterine tripolyphosphate. Attempt to Interpret the Biosynthesis of L-Sepiapterine
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The synthesis was achieved by phosphorylation of tetrahydro-5,6,7,8-D-neopterine with polyphosphoric acid.The product is sensitive to light, moisture and oxidation like the other tetrahydropterines.After oxidation in aqueous solution, D,L-sepiapterine was isolated in 5percent yield.The oxidation of non-phosphorilated tetrahydro-5,6,7,8-D-neopterine under the same conditions led to D-sepiapterine without inversion of the configuration.These findings were used to give a tentative explanation for the biosynthesis of natural L-sepiapterine from the D-neopterine.
- Antoulas, Simeon,Viscontini, Max
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- Chemoenzymatic Assembly of Isotopically Labeled Folates
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Pterin-containing natural products have diverse functions in life, but an efficient and easy scheme for their in vitro synthesis is not available. Here we report a chemoenzymatic 14-step, one-pot synthesis that can be used to generate 13C- and 15N-labeled dihydrofolates (H2F) from glucose, guanine, and p-aminobenzoyl-l-glutamic acid. This synthesis stands out from previous approaches to produce H2F in that the average yield of each step is >91% and it requires only a single purification step. The use of a one-pot reaction allowed us to overcome potential problems with individual steps during the synthesis. The availability of labeled dihydrofolates allowed the measurement of heavy-atom isotope effects for the reaction catalyzed by the drug target dihydrofolate reductase and established that protonation at N5 of H2F and hydride transfer to C6 occur in a stepwise mechanism. This chemoenzymatic pterin synthesis can be applied to the efficient production of other folates and a range of other natural compounds with applications in nutritional, medical, and cell-biological research.
- Angelastro, Antonio,Dawson, William M.,Luk, Louis Y. P.,Loveridge, E. Joel,Allemann, Rudolf K.
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