Total Synthesis Of Malyngamides K, L And 5″-epi-C

This thesis was concerned with the studies on the first and asymmetric total synthesis of malyngamides K, L, and 5"-epi-C. It mainly consists of the following three parts:First, the recent progress in research of vinyl chloride structural motif had been reviewed. Up to now,37 malyngamides had been isolated, in which 25 malyngamides bearing a vinyl chloride structural motif, and 15 malyngamides bearing a cyclohexenone ring or a heavily oxygenated six membered ring and a vinyl chloride structural motif. So an accelerated method to construct the vinyl chloride structural motif would be found to finish this malyngamides. In this part, we summarized the recent studies on the progress of the construction of vinyl chloride structural motif.In chapter 2, An accelerated, enantioselective, and general synthetic route to a class of malyngamides-K (1), L (3), and 5"-epi-C (4)-bearing a cyclohexenone ring or a heavily oxygenated six membered ring and a vinyl chloride structural motif was developed in detail. (-)-(4E,7S)-7-methoxytetradec-4-enoic acid, had been synthesized earlier by us using a Johnson-Claisen rearrangement as a key step. The amides containing chlorovinyl iodide functionality were prepared using Ogilvie's method from ethyl propiolate. Suzuki coupling reaction of two of them would furnish the skeleton of the target malyngamides. Starting from the synthesis of the relative simple malyngamide K to explore the general route, an Suzuki coupling reaction of amide with the vinyl chloride part and boronic acid in the presence of Pd(OAc)2, t-Bu3P·HBF4, and Cs2CO3 gave the skeleton of malyngamide K and finished the synthesis of it, Applied this route to the synthesis of malyngamides L and 5"-epi-C, SPhos was used as ligand. The determination of the absolute configuration of malyngamide L was also accomplished in the synthesis of it. The total synthesis of malyngamides K, malyngamide L, and 5"-epi-malyngamide C were accomplished via a highly convergent strategy in 7 steps in 23% yield, in 10 steps in 3.7% yield, and in 14 steps in 2.7% yield, respectively. This chapter also included several failed routes of total synthesis of malyngamides K, L, and C.In chapter 3, the total synthesis of isomalyngamide K and malyngamide M was tried in detail.The three target molecules of malyngamides were synthesized and the absolute configuration of malyngamide L was determined in this thesis which involved in the preparation of 53 new compounds. The synthesis of malyngamides bearing a cyclohexenone ring or a heavily oxygenated six membered ring and a vinyl chloride structural motif had been finished, and could provide materials for more extensive biological evaluation of those malyngamides. The synthetic methods in the thesis should extend the preparation of other structurally related malyngamides containing the similar structure and enrich the content of total synthesis of natural products and organic synthetic methodology.