Total Synthesis Of (+)-Valienamine And (+)-Valiolamine As Well As Synthesis And Application Of Stilbenes

This dissertation contains the following three parts:(1):Total syntheses of (+)-valienamine and (+)-valiolamine.(+)-Valienamine and (+)-valiolamine are two efficient glycosidase inhibitors, which can be used in treatment of diabetes. Therefore, it is of practical significance to develop new synthetic routes to these two compounds. Herein an common synthetic route to (+)-valienamine and (+)-valiolamine starting from (-)-shikimic acid was described. Firstly, compound Ⅰ-Ⅱ-1, as the key common intermediate, was first synthesized by eight step in 56% overall yield from (-)-shikimic acid, and then was converted to (+)-valienamine via three steps in 73% overall yield and (+)-valiolamine via two steps in 91% yield. Therefore, (+)-valienamine was prepared via eleven steps in 41% overall yield and (+)-valiolamine was prepared via ten steps in 51% overall yield from (-)-shikimic acid. The synthetic route featured short steps, high yields and use of readily available reagents.(2):Synthesis of 2-vinylstilbenes and their application in preparation of indenes.Indene is a priviledged structural motif in natural products, pharmaceuticals and molecules of materials. Indene and its derivatives have also been used as universal ligands for transition metal complexs. So the development of efficient methodology for synthesis of indenes is of considerable significance. Firstly,2-vinylstilbenes Ⅱ-Ⅱ-4(a-n) were efficiently synthesized in 71%-94% yields via base-promoted cascade eliminations of 1-benzylisochro-mans. Secondly, a series of indenes Ⅱ-Ⅱ-9(a-n) were prepared in 75%-92% yields via a PTS-catalyzed intramolecular cyclization reaction in CH2Cl2 or CHCl3 from 2-vinylstilbenes. Thirdly, isomerization of these indenes has been achieved by heating in pyridine to give another type of indenes Ⅱ-Ⅱ-12(a-n) quantitatively (>97%yield). Meanwhile, the mechanisms of the above reactions were also studied.(3):Preparation of stilbenes by regiospecifically introducing a styrene group at orth positions.Stilbenes have shown many interesting biological, optical and electronic activities. Synthetic route to stilbenes by regioselectively introducing one or two styrene groups into the aromatic ring was reported in the thesis. At first, N-tosyl-1-benzylisoquinolines Ⅲ-Ⅱ-4(a-p) were synthesized via Pictet-Spengler reactions in 77%-92% yields. Then a base-promoted intramolecular β-elimination took place to afford stilbenes Ⅲ-Ⅱ-7(a-p) in 70%-93% yields.The above two-step sequence is equivalent to the regioselsctive introduction of a styrene group via the ortho-orientation effect of the side chain on the aromatic ring. For some substrates, two styrenes could be introduced respectively on the two ortho positions by repeating the same procedures. Moreover, subsequent removal of Ts and half-equivalent chiral resolution of substrates Ⅲ-Ⅱ-4o and Ⅲ-Ⅱ-4p produced (S)-(-)-norlaudanosine and (S)-(-)-O, O-dimethylcoclaurine, respectively.