Question

. (a) An aliphatic aminoglycoside is relatively stable to base, but it is quickly hydrolyzed by dilute acid. Propose a mechanism for the acid-catalyzed hydrolysis.

(b) Ribonucleosides are not so easily hydrolyzed, requiring relatively strong acid. Using your mechanism for part (a), show why cytidine and adenosine (for example) are not so readily hydrolyzed. Explain why this stability is important for living organisms.

Short answer

a)

b)

Nucleosides require stronger acid, or higher temperatures to be hydrolyzed. This is important in living systems as it would cause genetic damage to an organism if its DNA or RNA were too easily decomposed.

Step-by-step solution

Step-1. Mechanism of acid-catalyzed hydrolysis of an aliphatic riboside:

An aliphatic riboside on acid-catalyzed hydrolysis produces hemiacetal form of ribose. Tertiary aliphatic amine which is present in the aliphatic riboside acts as a strong base and abstracts proton from the medium which leads to formation of positive charge on nitrogen atom, which is not stable, thus, the tertiary amine group leaves as a leaving group and carbocation is formed. This carbocation is stable due to mesomeric effect of nearby oxygen and then water acts as a nucleophile and attacks at carbocation. Then, after stabilisation of positive charge on oxygen, we get our required product.

Mechanism of acid-catalyzed hydrolysis of an aliphatic riboside

 Step-2. Importance of stability of nucleosides in living systems:

Nucleosides are less rapidly hydrolyzed in aqueous acid because the site of protonation that is, nitrogen in adenosine and oxygen atom with negative charge in cytidine is much less basic than aliphatic amine in aminoglycoside. Nucleosides require longer time, or stronger acid, higher temperature to be hydrolyzed. This stability is important in living systems as it would cause genetic damage or even death of the organism if decomposition of DNA or RNA takes place easily. Considerable energy is expended to maintain the structural integrity of DNA.