Physical Sciences and Mathematics Commons^™

The Design And Synthesis Of Farnesyl "Tail" Analogues Incorporating Aromatic Rings: A Comparison Of Wittig And Grignard Reaction Sequences, Mark F. Mechelke, Lisa Motschke, Todd Nichols, Sarah Albrecht

Chemistry Faculty Publications

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" …