Total Synthesis Of Malyngamides U, V And Conjugated Unsaturated Amide Alkaloids

This thesis is concerning on the synthesis of malyngamides U, V as well as the application of Ramberg-Backlund reaction to the synthesis of naturally occurring unsaturated amide alkaloids. Additionally, a novel reaction of α,β -unsaturated esters and ketones with lithium aluminum hydride was studied based on our group research. It mainly consists of the following four parts:First, we summarized the recent application of carvone which served as a narural chiral pool for the synthesis of malyngamides U and V in the synthesis of the natural products on the basis of the different function in construction of the skelecton. It was pointed out the importance of carvone in the natural product synthesis.In chapter 2, the total synthesis of malyngamides U, V was introduced detailedly. At first, a brief introduction of malyngamides was given. After that, a stereoselective synthesis of (-)-(4E,7S)-7-methoxydodec-4-enoic acid which is the acid portion of malyngamides U and V was accomplished in eight steps from hexanal in 24% overall yield. The key steps involved the catalytic asymmetric allylation of hexanal and the coupling reaction of a chiral alkyne and a protected bromide in the presence of t-BuLi. Then the structural revision and determination of absolute configuration of malyngamide U were presented by first total synthesis. Natural chiral pool (S)-carvone was selected as starting material. The key steps involved a hydroxymethylation of (S)-carvone and an asymmetric Henry reaction of key aldehyde. At last, the synthesis of malyngamide V was investigated. During the course Evans-aldol reaction was as the key step for the construction of the six membered ring of the amine portion.In chapter 3, based on the work of our lab, 13 naturally occurring unsaturated amide alkaloids bearing pyrrolidine, isobutyl and piperidine moieties and one analogue were synthesized by Ramberg-Backlund reaction.At last, a novel reaction of reduction of α,β-unsaturated esters and ketones with lithium aluminum hydride to afford 1,3-diol was presented based on our work. Direct application can be expected in the synthesis of the natural products containing 1,3-diol structural unit.