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Publication Title

Journal of Undergraduate Chemistry Research

Document Type

Article

Publication Date

Spring 2009

Abstract

Mutant RAS proteins have been linked to over 30 of all human cancers. It has been shown that mutant RAS proteins that cannot be farnesylated do not induce malignant transformation. Therefore, farnesyl protein transferase (FPTase) inhibitors have become attractive targets as potential chemotherapeutic agents. Two farnesyl "tail" analogues have been prepared that incorporate aromatic rings. One of the compounds, trans-9-phenyl-8-nonen-1-ol, could only be prepared pure using a Grignard reaction sequence. This sequence is compared to the initially attempted Wittig reaction sequence that results in an inseparable mixture of cis/trans isomers. It is anticipated thatwhen coupled with poal diphosphate "head" mimetics, the "tails" prepared in this pper will help illuminate the importance of nonbonding interactions in the binding of farnesyl pyrophosphate analogues to the FPTase enzyme active site.

Comments

NOTE: This is a PDF of the article as originally published in the Journal of Undergraduate Chemistry Research. It is archived here with the kind permission of the publisher. The original version was published as:

Mechelke, Mark F., Lisa Motschke, Todd Nichols, and Sarah Albrecht (2009). "The Design and Synthesis of Farnesyl "Tail" Analogues Incorporating Aromatic Rings: A Comparison of Wittig and Grignard Reaction Sequences," Journal of Undergraduate Chemistry Research, Vol. 8, No. 2. Available to subscribers at http://www.vmi.edu/WorkArea/DownloadAsset.aspx?id=4294970100.

NOTE: All of the student authors were enrolled in CHEM 489 - Independent Study and conducted the research for this article under the guidance of Dr. Mark Mechelke.

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