|Devlopment of Novel Synthetic Methodology
Projects in this area stem from our own needs for new organic
transformations or, more generally, from a recognized need in the
organic chemistry community for a new method. In the former vein, we
have developed new reagents for the guanylation of amines (i.e., their
conversion to guanidines) [link, link] and the protection of carboxylic acids as dimethylallyl (DMA) esters [link], link]
In the latter vein, we developed a novel, cyclic dipeptide catalyst for
an asymmetric version of the Strecker amino acid synthesis [link, link].
This latter finding led to a broad effort directed toward the use of
cyclic dipeptide catalysts in asymmetric carbon-carbon bond forming
reactions [link, link].
This work has been highlighted in Chemical and Engineering News (April
28, 1997; p. 26-27; May 19, 1997; p. 38-40). Current projects
involve the synthesis of macrocyclic lactams and thioesters on a solid
support as well as new methods for forming amide bonds.
|Design and Synthesis of Biologically Active Molecules
Research in this area can be thought of as "drug design." We have
earlier studied the cytotoxicity of the marine depsipeptide callipletin
B [link]. We have also made pseudopeptide inhibitors of the HIV-1 protease [link, link].
We have also studied the origin of the so-called “French Paradox” by
making a library of analogues of the phytoalexin resveratrol and
testing its ability to inhibit a number of biological targets [link, link].
Ongoing projects include the synthesis of inhibitors of the enzymes HMG
CoA Reductase – a novel target for antimicrobial design --and Ghrelin
O-Acyl Transferase the synthesis of novel DNA-cleaving agents for the
treatment of cancers, especially those leading to solid tumor
formation. Projects of this type usually involved computer-aided
molecular modeling, X-ray crystallography and enzyme inhibition studies.