The present invention relates to a novel method for synthesizing a polysubstituted
pyridine derivative and, more specifically, to a method for synthesizing a 2,3,5-substituted
pyridine derivative through a specific ring cleavage reaction. In the synthesis method of the present invention, an
enamine structure is formed in situ by using beta keto ester /
sulfone / phosphonic acid ester and
ammonium acetate and subjected to an
aldol condensation reaction with 3-formyl (aza) indole /
benzofuran, a cyclization reaction, and a ring-cleavage reaction in that order to synthesize a characteristic
pyridine structure having an
alkyl /
aryl substituent attached to the 2-position thereof, an ester /
sulfone / phosphonic acid ester attached to the 3-position thereof, and ortho-aminoaryl /
phenol including various substituents attached to the 5-position thereof. In particular, (aza)indole /
benzofuran and beta keto ester /
sulfone / phosphonic acid ester, which are reaction substrates, are substrates having very high
accessibility, and enable the introduction of various substituents, thereby constructing a pyridine skeleton having high
biocompatibility into which ortho-aminoaryl or
phenol substituents having various substituents are introduced.