Synthesis Of Marine Natural Product Apratoxin E

Cyclic peptides including cyclic depsipeptides are still a growing research area even in the 21 st century.Most of them will offer a new frontier in both synthetic organic chemistry and biological activities.However,generally speaking,it is rather difficult to isolate a larger amount of marine natural products because of minute constituents in organisms,difficulty of collection of organisms,and resistance of laboratory culturing.Thus,the total synthesis is still playing a final means for the structure determination of marine natural products just like several decades ago.Furthermore,the efficient large-scale production of marine natural products by synthesis will offer an opportunity to investigate their biological activities in detail.In addition,unusual amino acid and non-amino acid moieties of marine cyclic peptides will offer the lead structures of new biologically useful compounds.This dissertation is constituted of the following two parts:Part one: Synthesis of Apratoxin E,30-epi-Apratoxin E and configurational reassignment.1.An asymmetric synthesis of 161 using(R)-CBS-catalyzed asymmetric reduction(dr=88:12)from lactone 163,isolated from industrial waste water,was completed in 19% overall yield.2.Asymmetric synthesis of Apratoxin E was completed.Olefin cross-metathesis(CM)was applied as an alternative approach for the formation of the double bond.Macrocyclization was completed at C6-N use HATU as condensation agent in 19% yield.3.Macrolactamization use FDPP as condensation reagent afforded apratoxin E in 43% yield.4.30-epi-Apratoxin E was synthesized to determine the absolute configuration of Apratoxin E.Part two: Divergent large scale synthesis of hydroxyethylene isostere1.The synthesis of the imine 315 utilize Evan's alkylation as key step from glutamate derivative 306 was was completed in 6.5% overall yield.2.Six analogues of hydroxyethylene isostere was synthesized using the one-pot intramolecular tandem proptocol.