Synthesis And Manipulation Of Carbasugars And Natural Product Scaffolds

Abstract

My doctoral studies have focused on the construction of natural products and diversification of complex natural product scaffolds. A specific natural product with interesting bioactivity, sch202596, an antagonist for the galinin receptor, contains two moieties that formed the basis for my graduate studies: a carbasugar and a spirocoumaranone (dienone). Work, therefore, focused on two areas: (1) asymmetric regio-resolution of allylic oxides for the synthesis and incorporation of spirocyclization. carbasugars; and (2) asymmetric hypervalent iodide oxidative A system was developed in which a racemic allylic oxide underwent a Tsuji-Trost allylation to yield four different enantioenriched regioisomers which were carried onto four different carbasugar natural products: streptol, MK7607, cyathiformine B and polyporapyranone G. This method, termed allylic oxide regio resolution (AORR), allowed for the control of product distribution through prudent ligand and protecting group selection. Additionally, AORR allowed for the incorporation of carbasugars into phenolic natural product scaffolds. Rubiyunnanin B, a glycosidic macrocyclic peptide with an interesting bioactivity profile was one particular natural product scaffold which could be subjected to AORR. A short synthesis of the rubiyunnanin B aglycone was developed and 1H NMR analysis was used to determine the overall structure of the core. The second area of research resulted in the synthesis of arnottin II through hypervalent iodine mediated oxidative spirocyclization.