Total Synthesis Of Spirotryprostatin A,Spirotryprostatin B And Fumitremorgin B

Spirotryprostatin A and Spirotryprostatin B are two bioactiveindole alkaloidsisolated from thefermentation broth of Aspergillus fumigates inl996.Both compounds were shown to inhibit the cell cycle in the G2/M phase.Spirotryprostatin B also inhibits the growth of human chronicmyelogenous leukemia K562 cells and human promyelocyticleukemia HL-60 cells.Fumitremorgin B,a mycotoxin isolated from Penicillum simplissimum,is a structually unique and potentially biologically compound of mycotoxins.Fumitremorgin B could induce sustained tremors in animals.Recent studies indicated that the fumitremorgins displaypotent activity against multi-drug resistant (MDR) cancer celllines.All above mentioned compounds are characterized by the presence of 2,5-diketopiperazine ring formed from L-tryptophan and L-proline.lts biological significance as well as structural novelty has long attracted the attention of numerous investigatorsto develop synthetic strategies towards these natural products and its analogues.This dissertation focuses on the studies of new synthetic method for the preparation of 2,5-diketopiperazines and the total synthesis of Spirotryprostatin A,Spirotryprostatin B and Fumitremorgin B.It consists of five chapters.In chapter 1,the advance of isolation,biological activity and total synthesis of 2,5-diketopiperazines indole alkaloids are summarized.In the second chapter,we developed a new method for the efficient synthesis of enamide unitcontaining 2,5-diketopiperazines.This synthetic method provides 2,5-diketopiperazines with an useful acrylamide moiety which can be applied to the synthesis of many natural products and analogues.The study of this chapter shows that trimethylphosphinecan promote the reaction between alkynamidesand general amides.The best additive is sodium glutamate.In order to study the substrate scope,more than twenty a-Ylidene-2,5-diketo-piperazines were synthesized under the optimal reaction condition.Our method was compatible to a number of functional groups such as Boc,,OTBS,vinyl and nitro groups.In chapter 3,studies towards the total synthesis of spirotryprostatin A and spirotryprostatin B is described.The quaternary carbon centers presented in those natural products were constructed based on copper catalyzed arylation of o-bromoanilide derivatives.In chapter 4,the total synthesis of fumitremorgin B was studied based on our synthetic method of 2,5-diketopIperazines.Completed pentacychc core skeleton of the natural product Fumitremorgin B.In chapter 5,experiment procedure,physical and spectrum data for new compounds are recorded.