合成L-sugar的新方法及利用D-(-)-quinic acid經Beckmann rearrangement合成trihydroxyazepanes

A new synthesis of L-sugar and the use of D-(-)-quinic acid for synthesis of trihydroxyazepanes via Beckmann rearrangement.

曾瑞晃(Jui-Huang Tseng)

指導教授 ： 施增廉

淡江大學/理學院/化學學系碩士班/碩士(2005年)

https://doi.org/10.6846/TKU.2005.00091

摘要

近年來，由於L-carbohydrate在醫學界的應用，引起了許多的注意，故有許多文獻報導。
我們設計了由D-mannono-1,4-lactone為起始物，經過5個合成步驟合成了L-allono-1,4-lactone，其重要的方法在於一步反應過程裡，連續進行了兩次反轉立體位向，使得D-mannono-1,4-lactone中的C-4及C-5的立體方位改變，而得到L-allono-1,4-lactone。
另外，由於azasugars在醫學上的應用，它們扮演著一個重要的角色，就是能夠抑制醣水解酵素。它們被認為能夠用來治療癌症、病毒感染及糖尿病等症狀，且具有潛力可發展成為新藥物。許多有關azasugar的文獻報導，其中以五圓環(pyrrolidine)、六圓環(piperidine)為最多，而七圓環的azepane最少。而所合成7圓環azepanes中，又以tetrahydroxyazepanes最多、trihydroxyazepanes次之、dihydroxy-azepanes為最少。
由D-(-)-quinic acid為起始物，利用Beckmann rearrangement反應得到具保護基之七圓環azasugar，進一步在去除保護基即可獲得trihydroxyazepane。

關鍵字

L-醣類 ； 重排反應

並列摘要

Recently, L-carbohydrate have been widely used in drug development. We reported herein an efficient synthesis of L-allono-1,4-lactone from D-mannono-1,4
-lactone in five-step sequence. The key feature of the method involved a one pot "double inversion” procedure at stereocenter of C-4 and C-5 of D-mannono-1,4
-lactone to obtain the L-allono-1,4-lactone.
On the other hand, azasugars played an important role as glycosidase inhibitors. They were used in treatment of cancer, viral infection and diabetes, and have potential to make new drugs.
There are many reports to azasugars which they focused much attentation on the preparation of various five- and six-member azasugars namely polyhydroxy pyrrolidine and piperidine, respectively. However, only a few reports have appeared to the synthesis of seven-member azasugar-azepanes. Tetrahydroxy-azepanes appeared most in literatures among seven-member azasugars. Only few cases of trihydroxyazepanes and dihydroxyazepanes were described. Two trihydroxyazepanes were synthesized via Beckmann rearrangement from readily available D-(-)-quinic acid and reported in this article.

並列關鍵字

L-sugar ； azepanes ； Beckmann rearrangement

參考文獻

6. Qian, X.; Morís-Varas, F.; Fitzgerald, M. C.; Wong, C.-H. Bioorg. Med. Chem. 1996, 4, 2055-2069.

Foglietti, M.-J. Bioorg. Med. Chem. 1997, 5, 519-533.

9. Johnson, H. A.; Thomas, N. R. Bioorg. Med. Chem. Lett. 2002, 12, 237-241.

11. Jung, M. E.; Xu, Y. Tetrahedron Lett. 1997, 38, 4199-4202.

Kojima, F.; Takeuchi, T. J. Org. Chem. 2000, 65, 4871-4882.