Studies toward the Asymmetric Synthesis of Azasugars

氮杂志如多羟基氮杂志、幽门螺杆菌和吡啶，是来自不同植物、细菌和其他组织的独特类别的天然产品，这些有机产品在抗艾滋病毒活性和抗肿瘤活性中表现出潜力。该项目中氮杂志分子的目标是代谢酶（1）（抗体活动），阿扎里博斯（2）（拮抗剂活动），BM-1（3）（双歧杆菌分化-促进活动），异法明（4）（葡萄糖苷酶抑制剂活性）和自然吡咯烷苷生物碱，Broussonetine C （5）和Lentiginosine （6）.在我们的路线上的关键步骤（1）将柑橘类化合物通过脂质催化的动力学溶液进行高度区域性的减少。一种不对称的方法（2）是基于对称性二氢xysuccimides的酶分化的策略。（3）的综合征是由相应的羟基氮杂卓的有效氧化法完成的。（4）对脂酶催化的不对称诱导的1，3-丙二醇衍生物和合成的方法。不饱和的吡啶-2-1的立体二羟基化。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 Ety D23 y D2SiH.We developed a new、practical、methodology for the total synthesis of （1）、（3）、（5）和（6）。

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).