Asymmetric Total Syntheses Of Alkaloids (-)-Robustanoids A,B And (+)-Cylindricines C,D,E

Alkaloids,mainly found in plants,are a class of nitrogenous secondary metabolites,most of which have complex cyclic structures and an extremely wide distribution.They usually have important biological activities and play an important role in the fight against diseases in humans,and have been widely studied by scientists.This thesis is based on DMDO-triggered tandem cyclization and reductive alkylation of lactams strategy,we implement asymmetric total synthesis of(-)robustanoids A,B and(+)-cylindricines C,D,E,consisting of the following two parts.1、Asymmetric total synthesis of(-)-robustanoids A,B and analogs.(Chapter 2)Designed by using methyl L-tryptophanate derivative I as starting material to realize "one pot" consists of DMDO-triggered tandem cyclization strategy and Trost’s regioselectivity-umpoling methodology("anti-Michael addition")without protection,we explored a concise and flexible approach to(-)-robustanoids A,B and analogs[(-)robustanoid B is completed in 3 steps with 32%;(-)-robustanoid A is completed in 4 steps with 31%].2.Enantioselective total syntheses of marine natural products(+)-cylindricines C,D,E and their diastereomers.(Chapter 3)Based on reductive dialkylation of lactams strategy by our recently improved protocol to build the N-α-tert-alkyl motif,and a telescoped one-step four-reaction protocol:1.Lindlar-catalyzed to generate enone;2.TFA removes N-Boc and O-TBS protection in one step;3.Construction of tricyclic skeleton by an intramolecular azaMichael addition under alkaline conditions.Starting from the lactams Ⅴ or Ⅵ,(+)cylindricines C,D,E and their diastereomers are completed in 7-9 steps with 18.5-20.9% overall yield.