Chapter 25, Problem 4PP

Interpretation Introduction

Interpretation:

The type of linkage involved in acetonide formation is to be determined and the reason for its susceptibility to acidic hydrolysis and its formation is to be explained.

Concept introduction:

舧 Electrophiles are electron-deficient species, which has positive or partially positive charge. Lewis acids are electrophiles, which accept electron pair.

舧 Nucleophiles are electron-rich species, which has negative or partially negative charge. Lewis bases are nucleophiles, which donate electron pair.

舧 A nucleoside consists of a nucleobase (also termed as nitrogenous base) and a five-carbon sugar (either ribose or deoxyribose).

舧 A nucleotide consists of a nucleobase (also termed as nitrogenous base), a five-carbon sugar (either ribose or deoxyribose) and one or more phosphate groups.

舧 In a nucleoside, the anomeric carbon is linked through a glycosidic bond to the N9 of a purine or N1 of a pyrimidine.

舧 Examples of nucleosides include cytidine, uridine, adenosine, guanosine and thymidine.

舧 Sugar (ribose/deoxyribose) and nitrogenous bases are linked through N-glycosidic bonds.

舧 These glycosidic bonds are formed by condensation reaction of first carbon of sugar molecule with the nitrogen atom $(\text{N1 of pyrimidines and N9 of purines)}$ of the nitrogenous base.

舧 This particular glycosidic bond is stable in basic solutions, but readily hydrolyzes in the presence of acids.

舧 Protection of hydroxyl group at C-2 and C-3 of ribose sugar can be done by treating it with a carbonyl compound. The two alcohol groups behave as diol and react with carbonyl to form cyclic acetal.

舧 In case the carbonyl involved is acetone, it is called acetonide.

舧 Such groups are stable to bases, but are readily hydrolyzed in mild acids.

舧 The structure of acetonide indicates cyclic diether, in which the alkoxy groups are connected through a single carbon atom and any carbon having two alkoxy groups is said to have involved in acetal formation.

舧 It is susceptible to mild acidic hydrolysis because, in acidic conditions, protons attack the alkoxy oxygen and protonate them. This results in the weakening of the bond of carbon to alkoxy, which readily hydrolyzes.

舧 The acetonide can be formed by the reaction of acetone with a nucleoside in acidic conditions. The proton liberated by the acidic group mediates an electrophilic attack on the carbonyl oxygen, which results in protonation. The protonated product further attacks the nucleoside and produces acetonide.