Synthesis of Novel Anti-Cancer Compounds Based on Sphingolipid Analogs Open Access

Kouanda, Abdul Moro (2010)

Permanent URL: https://etd.library.emory.edu/concern/etds/hq37vn705?locale=en
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Abstract

Abstract
Synthesis of Novel Anti-Cancer Compounds Based on Sphingolipid Analogs
By Abdul M. Kouanda
Sphingosine is a compound that induces apoptosis in cancer cells, including androgen independent
prostate cancer. It fails in that its primary hydroxyl group is phosphorylated in vivo by sphingosine kinase.
Collaboration with Dr. Dennis C. Liotta of Emory University and Dr. Alfred H. Merril of Georgia Tech have
developed a 1-deoxysphingolipid derivative, enigmol. Enigmol is more potent against tumor cells than
sphingosine because it is not metabolized as quickly. In this thesis, a proposed synthesis of novel 1-
deoxysphingolipid compounds, as potential anti-cancer compounds, is explored. The building blocks of
these novel analogs, including their direct precursor, have been successfully synthesized and fully
characterized by 1H NMR, 13C NMR, FT IR, and HRMS. Our proposed synthesis approach has been a
difficult, but successful method and we are at the dawn of the synthesis of the first of these analogs.

Table of Contents

Table of Contents

1. Introduction ........................................................................................................................... 1
2. Research Methods .................................................................................................................. 4
3. Experimental .......................................................................................................................... 4

3.1 General methods .......................................................................................... 2
3.2 Synthesis of epoxy alcohol 1 ......................................................................... 2
3.3 Synthesis epoxyazide 2 ................................................................................. 2
3.4 Synthesis of lipid section 5 ............................................................................ 2
3.5 Alternate synthesis of lipid section 5 ............................................................ 2
3.6 Removal of TMS group 6 ............................................................................... 2
3.7 Synthesis of alkynylhydroxyazide intermediate 8 .......................................... 2
3.8 Synthesis of spisulosine analog 9 .................................................................. 2
3.9 Synthesis of alternate spisulosine analog 10 ................................................. 2
Discussion .................................................................................................................................. 4
Conclusion .................................................................................................................................. 4

Figures
Figure 1A .................................................................................................................................... 2
Figure 1B .................................................................................................................................... 2
Figure 2....................................................................................................................................... 3
Figure 3....................................................................................................................................... 4
Figure 4....................................................................................................................................... 5
Figure 5....................................................................................................................................... 7

Figure 6....................................................................................................................................... 7
Figure 7....................................................................................................................................... 9
Figure 8..................................................................................................................................... 10
Scheme 1 .................................................................................................................................... 2
Scheme 2 .................................................................................................................................... 2

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