Synthesis of carbohydrate related compounds by using aldolase catalyzed reaction

Enzymes proceed the reaction with high regio- and stereoselectivity under m ild conditions, ie. in an aqueous medium at room temperature. However, enzy matic reactions that catalyze carbon-carbon bond formation have not been ut ilized in organic synthesis until recently. We had an interest in an aldola se-catalyzed reaction which proceed carbon-carbon bond formation referred t o aldol condensation, by which many bioactive compounds have been rationall y synthesized. On the other hand, recent biological studies on cell recogni tion (cell adhesion) have disclosed the important roles of oligosaccharides on cell surfaces, especially which include glucuronic acid, 3-deoxy-D-mann o-oct-2-ulosonic acid (KDO), and sialic acid in the structures e.g. sialyl Lewis X and endotoxins, in differentiation, induction, viral and bacterial infections, and immune response. As well as acidic oligosaccharides, basic ones have been utilized as practical medicines in the clinical level, like acarbose that acts as an amylase inhibitor. Based on these background, we e mbarked the synthesis of carbohydrate related compounds which can control t he interaction between carbohydrates and carbohydrate recognition protein b y the use of several aldolases. Azasugars, potent inhibitors toward glycosi dases, were synthesized using fructose-1,6-diphosphate (FDP)-aldolase and o ther dihdroxyacetonephosphate (DHAP)-dependent aldolases in the key step. S ialyl Lewis X mimetic, peptidic mimetic of RNA having anti-Vero toxin activ ity, mycestericin D, and aza-idulonic acid were prepared by taking advantag e of L-threonine aldolase catalyzed reaction, which afford beta-hydroxy-alp ha-L-amino acids. A precursor of KDO, featured acidic sugar of endotoxins w as provided by the reaction catalyzed with kynureninase, which generates be ta-anion of L-alanine in its active site during the metabolic reaction from kynurenine to anthranilic acid.