The Attempted Synthesis of Carba-Nicotinic Acid Mononucleotide Methyl Ester using the Zincke Rea

According to the retrosynthetic analysis, the carba-nicotinic acid mononucleotide methyl ester can be synthesized from a nucleoside made using a primary amine and a Zincke salt by the Zincke reaction. The primary amine which was the cyclopentane analog of 1-aminoribose was synthesized following the procedure described by Cermak and Vince in 1981 starting from the Vince lactam. The pyridinium part was synthesized as a Zincke salt. However carba-nicotinic acid mononucleotide methyl ester cannot be synthesized using this procedure due to the unanticipated high reactivity of the nicotinic acid esters with primary amine during the Zincke reaction. We found that pyridinium-3-carboxylic esters reacted rapidly with amines resulting in the formation of amids. A series of Zincke reaction were performed to study the Zincke reaction. Even the most sterically hindered protecting group tert-butyl ester could not prevent the formation of nicotinamide.