Areas of Research Interest:
Synthetic Methodology and Medicinal Chemistry
Picture of me working with a student in the lab

My students and I have been exploring practical approaches to stereoselectively introducing a C-24 hydroxyl group to the steroidal side chain because many biologically important molecules contain 24R or 24S-hydroxyl group. Our research showed that the cholest-22-yne-24-one system is readily reduced by (R)-Me-CBS complex to stereoselectively (>94% de) afford the 24S-propargylic alcohols. Hydrogenation of the resultant propargyl group delivered the 24R-hydroxylated cholestanes. Our method provides one of the most straightforward approaches to the stereoselective synthesis of the C24-hydroxylated steroid sidechain, which is an integral structural feature of molecules such as squalamine, cholesterol metabolites, and Vitamin D3 metabolites and analogs. Having developed this methodology, we are currently synthesizing a variety of steroidal analogs to test the generality of the stereoselective reduction.

M. N. Rao, M. A. McGuigan, X. Zhang, W. A. Kinney*, M. Bulliard, B. Laboue, N. E. Lee* J. Org. Chem. 1997, 62, 4541;
N. E. Lee, G. S. Reddy, A. J. Brown, P. G. Williard Biochemistry 1997, 36, 9429;

"Chiral Reduction of a Steroidal a,b -Alkynone side Chain", Annise P. Berger, Nancy E. Lee.
27th Northeast Regional Meeting of the American Chemical Society, Sarotoga Springs, NY. June 1997.]

"Chiral Reduction of Steroidal a,b-Alkynone Side Chains", T. B. Gooding, A. P. Berger, N. E. Lee
216th National Meeting of the American Chemical Society, Boston, MA. August, 1998.

"Chiral Reduction of a Steroidal a,b-Alkynone t-Butyl side Chain", Ayako Honda, T. B. Gooding, A. P. Berger, N. E. Lee.
Northeast Student Chemistry Research Conference, M. I. T., Cambridge, MA. April 1999.

 

Our second project involves studies toward synthesis of cyclic allylic imidates and their [3,3] sigmatropic rearrangement in a novel ring expansion reaction to produce medium size lactams. As a prerequisite for investigating the [3,3] rearrangement, the synthesis of five and six-member cyclic imidates was required. We synthesized 5-hydroxypentanenitriles and 4-hydroxybutanenitriles to study the intramolecular cyclization process under basic conditions. 4-hydroxybutanenitriles were more facile and cyclized to afford the desired five-member cyclic imidates. Several five-member cyclic allylic imidates were synthesized and we are currently studying the proposed [3,3] rearrangement to a seven-member ring lactams.

"Base-catalyzed cyclization of a hydroxy pentanenitrile" Kieuchinh T. Tran, Nancy E. Lee.
35th Annual American Chemical Society Undergraduate Research Symposium, Boston University, Boston, MA. April 27, 1996.

"Study of Synthesis and Rearrangement of Cyclic Imidates" Kathryn Schreiber, Yilin Shao, Natalie Hill, Kiieuchinh Tran, Nancy Lee. 216th National Meeting of the American Chemical Society, Boston, MA. August, 1998.

(Note: Simmons undergraduate co-workers are underlined)