Study On The Rearrangement Reaction Of Spiro Indole Oxides

Skeleton rearrangements are very common phenomenon in natural product biosythesis,which provide possibilities for the formation of natural products with diverse structures.Skeleton rearrangements,especially 1,2-shift rearrangement,are also widely used in the chemical synthesis of natural products.Up to now,more than 20 kinds of 1,2-shift rearrangements have been developed.Among which the Wagner-Meerwein rearrangement is driven by the stability of carbon cations.It was firstly found in the conversion from isoborneol to camphene.Because the rearrangement reaction is environmentally friendly,easily to handle,and usually facile,it plays an important role in organic synthesis especially in the total synthesis of natural products.Tetrahydro-o-carboline is the basic motif of the alkaloids of corynanthe.Corynanthe-type alkaloids which is not only an important kind of monoterpene indole alkaloids,but also a kind of important precursors for the biosynthesis of other monoterpenoid indole alkaloids.Moreover,they are featured with significant biological activities,such as antitumor,antiarrhythmic,hypotensive,anti-inflammatory,and antimalarial activities.Some of them have been developed into drugs and were widely used in clinical practice.Therefore,it is important to develop highly efficient strategies for constructing the tetrahydro-o-carboline structural skeleton,which will promote the subsequent medicinal studies of corynanthe-type indole alkaloids.In the first chapter,the Wagner-Meerwein rearrangement reaction was introduced,and its application in total synthesis of natural products was summarized.In the second chapter,3-spirooxindole substrates converted into tetrahydro-?-carboline derivatives by Wagner-Meerwein rearrangement reaction under the condition of trifluoroacetic acid(TFA)were reported.The effects of protecting groups,acids,and solvents on the rearrangement reaction were examined and the optimal reaction condition was determined.In addition,a series of 3-spirooxindole substrates with diversal functional groups have been prepared to test the substrate scope of this key transformation.The results indicated that the functional groups were well tolerated and resulted in good yields for nine tetrahydro-?-carboline derivatives.The success of this methodology enriched the synthetic methodology for the corynanthe-type monoterpenoid indole alkaloid.