Studies toward the Asymmetric Synthesis of Azasugars

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The azasugars such as polyhydroxy azetidines, pyrrolidines and piperidines, are a unique class of natural products isolated from various plant, bacteria and other organisms which exhibit potent in anti-HIV activity and antitumor activity.The target molecule of azasugars in this project are Jatropham (1) (antitumor activity), Azaribose (2) (antagonist activity), BM-1 (3) (bifidobacterium division-promoting activity), Isofagomine (4) (glucosidase inhibitory activity), and natural pyrrolidine alkaloids, Broussonetine C (5) and Lentiginosine (6).The key step in our route to (1) incorporates a highly regioselective reduction of citraconimide followed by a lipase-catalyzed kinetic resolution. An asymmetric approach towards (2) is based on a strategy of enzymatic differentiation of the symmetrical dihydroxysuccimides. The synthesis of (3) is accomplished by the effective oxidation of the corresponding hydroxyazetidine. The approach to the synthesis of (4) involves the lipase-catalyzed asymmetric induction of 1,3-propanediol derivatives and. the stereoselective dihydroxylation of the unsaturated piperidin-2-one. The key part of the synthesis of (5) and (6) is the nucleophilic addition of Grignard reagent to tataric C2-imide followed by the stereoselective deoxgenation by EtィイD23ィエD2SiH.We developed a new, practical, methodology for the total synthesis of (1), (3), (5), and (6).