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Site-Specific Oxidations of Organic Compounds in Water
EPA Grant Number: U915567Title: Site-Specific Oxidations of Organic Compounds in Water
Investigators: Yang, Jerry C.
Institution: Columbia University
EPA Project Officer: Thompson, Delores
Project Period: September 1, 1999 through September 1, 2002
Project Amount: $102,000
RFA: STAR Graduate Fellowships (1999)
Research Category: Academic Fellowships , Fellowship - Chemistry and Materials Science , Engineering and Environmental Chemistry
Description:
Objective:The objectives of this research project are to: (1) develop biomimetic catalysts that imitate enzymes, which would greatly aid the synthesis of organic substances such as pharmaceuticals due to their high selectivity, good turnover, and high catalytic rate; (2) develop novel synthetic methods of functionalizing steroids with high regio- and stereo-selectivity to gain access to some of these cholesterol degradative products that currently are only available through the wasteful process of microbial fermentation; and (3) develop efficient methods of producing highly potent natural and unnatural steroid compounds for use as drugs.
Approach:The first stage of this project entails development of a catalyst that could perform hydroxylations on steroids and steroid derivatives with high selectivity and catalytic turnover. The natural enzymes responsible for such reactions come from the Cytochrome P-450 class of enzymes. These enzymes contain a heme-protoporphyrin IX prosthetic group acting as the functional core that delivers a hydroxyl group to a hydrophibically bound substrate. Because metalloporphyrins have been shown to perform oxidation reactions in both enzymatic and nonenzymatic systems, a catalyst was designed using these readily available compounds as the functional core. One to four cyclodextrins are attached to the porphyrin scaffold, which produces a hydrophobic binding pocket that could selectively hold substrates in a specific geometric position to deliver a hydroxyl group to a single site.
By synthesizing new derivatives of steroids, it is hoped that the geometry of the catalyst-substrate complex will be changed and thus achieve higher selectivity for extremely inaccessible and otherwise unfavorable reactions. The investigators also are in the process of developing a new form of the catalyst that will have a better defined binding pocket that should help to obtain higher specificity. Although developing novel methods of making highly oxidized steroids is the primary objective, methods of selectively oxidizing other natural products for their potential use as commercial drugs also are being explored. Again, the novel synthetic method of binding substrates in a particular geometry will be used to form natural and unnatural byproducts of compounds such as vitamins and the carotenoids. It is hoped that this new methodology will allow scientists to gain access to important yet chemically inaccessible compounds.
Supplemental Keywords:fellowship, hydroxylation, cytochrome P-450, catalyst, hydrophobic, steroids.