Research

Polycyclic ether natural products:

We aim to establish efficient synthetic routes to a variety of cyclic and polycyclic ether marine natural products, represented by the triterpenes thyrsenol and abudinol (anticancer activity), as well as brevenal (blocks neurotoxic activity of red tide toxins).

thyrsenol

abudinol

brevenal

Our synthetic approaches feature regio- and stereoselective oxacyclization transformations, including a preparation of abudinol B that  is inspired by likely biosynthetic pathways.

abudinol synthesis 300

Acyclic and macrocyclic natural products:

We are developing two mechanistically unique strategies for the preparation of acyclic and macrocyclic natural products.  The first program is based on iterative couplings of epoxyalkyne modules, applied to the total synthesis of the anticancer natural product RK-397, as well as a substantial substructure of aflastatin.

RK397

aflastatin

The second program is based on stereospecific pericyclic rearrangements for the simultaneous construction of up to three elements of stereochemistry (one or two chiral centers combined with alkene stereochemistry).  This enabling methodology has been applied in preparing two substructures of the sphingolipid biosynthesis inhibitor, fumonisin B1.

fumonisin

We have also completed a unique synthesis of the anticancer natural product fostriecin.

fostriecin

Oligosaccharides:

We have invented a mechanistically novel cycloisomerization method for the preparation of cyclic enol ethers, with applications to several oligosaccharide and C-arylglycoside natural products, including the cardiotonic drug digitoxin, an anticancer natural product altromycin, and the antibacterial natural product saccharomicin.

digitoxin

altromycin

saccharomicin

Following up on a serendipitous discovery, we have initiated a program directed toward the preparation of the non-natural oligoseptanoside isomers of cellulose and starch, with potential application as biomaterials.

septanosides