Date of Award

Spring 1-1-2013

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry & Biochemistry

First Advisor

Marvin H. Caruthers

Second Advisor

Robert Kuchta

Third Advisor

Art Pardi

Fourth Advisor

Tad Koch

Fifth Advisor

Francine Wincott

Abstract

Phosphonoacetate RNA dimers and oligomers were synthesized using solid phase synthesis. Two different, orthoganol approaches were used for the 2’ and 5’ oxygens of the phosphoramidite synthons in order to maintain the phosphonoacetate linkage upon 2’-O deprotection. The first utilized a 2’-O-silyl protection (fluoride labile) along with a 5’-O-DMT protection (acid labile). The second path used an inverse 2’-O-ACE (acid labile) protecting group along with a 5’-O-silyl protection strategy. An additional emphasis in this dissertation was on the solid phase synthesis of unmodified RNA using a two-step cycle. The synthesis was performed using a 5’-O-carbonate-2’-O-1,3-Benzodithiolylium (BDT) protected synthon. During synthesis a peroxy anion buffer removes the 5’-carbonate protection and simultaneously oxidizes the internucleotide phosphite linkage. Following synthesis and removal from support the 2’-O-BDT group was removed. All products were then isolated and characterized.

Included in

Chemistry Commons

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