Studies toward the Asymmetric Synthesis of Azasugars

阿扎糖的不对称合成研究

• 批准号: 10650846
• 负责人: TAKABE Kunihiko
• 金额: $ 2.18万
• 依托单位: Shizuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10650846/
• 关键词: Azasugar; Imide; Asymmetric synthesis; Biologically active alkaloid; Enzymatic reaction; Azetidine; Pyrrolidine; Piperidine; 酵素的不斉識別; 位置選択的還元; Grignard試薬付加; キラルイミド誘導体

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).

诸如多羟基氮杂丁物，吡咯烷和吹笛的azasugars是来自teria和其他生物的auarural-auroural-anders，它们在抗窒息性和抗肿瘤活性中表现出有效。 ，azaribose（拮抗剂活性），BM-1（3）（双歧杆菌分裂活性），同造型（4）ASE抑制活性）和天然的吡里氨酸生物碱，broussonetine c（5）和扁豆s和倾斜类（6）。我们到（1）的途径包括高度的区域分辨率（4）涉及1,3-丙二醇衍生物的脂肪酶的不对称指征，饱和piperidin-2-one。 Et I D23 Yi D2SIH的Tereo选择性DECGINATION。我们开发了一种新的，实用的方法，用于（1），（3），（5）和（6）的总合成。

项目成果

H. Yoda, M. Kawauchi, and K. Takabe: "Novel asymmetric synthesis of an Indolizidine Alkaloid, (+)-Lentiginosine Employing Highly Stereoselective Hydrogenation of a-Hydroxypyrrolidine"Synlett.. (2). 137-138 (1998)

H. Yoda、M. Kawauchi 和 K. Takabe：“利用α-羟基吡咯烷的高度立体选择性氢化，新型不对称合成吲哚里西啶生物碱，()-Lentiginosine”Synlett.. (2)。

H. Yoda, T. Shimojo, and K. Takabe: "Asymmetric Synthesis of Tetrasubstituted Tetrahydrofuran, 2-Epigoniothalesdiol, Employing Stereoselective Hydrogenation"Synlett.. (12). 1969-1971 (1999)

H. Yoda、T. Shimojo 和 K. Takabe：“采用立体选择性氢化反应四取代四氢呋喃、2-表庚二醇的不对称合成”Synlett.. (12)。

H.Yoda: "First total synthesis of Tetrasubstituted Tetrahydrofuran Lignan,(-)-Virgatusin"Tetrahedron Letters. 40. 4701-4702 (1999)

H.Yoda：“四取代四氢呋喃木脂素，(-)-Virgatusin 的首次全合成”四面体快报。

H.Yoda: "Novel asymmetric synthesis of an indolizidine alkaloid (+)-Lentiginosine" Synlett.(2). 137-138 (1998)

H.Yoda：“吲哚里西啶生物碱 ()-Lentiginosine 的新型不对称合成”Synlett.(2)。

N.Mase: "First synthesis of (R)-(-)-5-hydroxy-3-methyl-3-pyrrolin-2-one(jatropham) by lipase-catalyzed kinetic resolution"Tetrahedron;Asymmetry. 10. 4469-4471 (1999)

N.Mase：“通过脂肪酶催化的动力学拆分首次合成 (R)-(-)-5-羟基-3-甲基-3-吡咯啉-2-酮（麻疯树）”四面体；不对称性。