Q67P H. G. Khorana won the Nobel Priz... [FREE SOLUTION]

Chapter 23: Q67P (page 1257)

H. G. Khorana won the Nobel Prize in Medicine in 1968 for developing the synthesis of DNA and RNA and for helping to unravel the genetic code. Part of the chemistry he developed was the use of selective protecting groups for the 5鈥� OH group of nucleosides.
The trityl ether derivative of just the 5鈥� OH group is obtained by reaction of the nucleoside with trityl chloride, MMT chloride, or DMT chloride and a base like Et₃N. The trityl ether derivative can be removed in dilute aqueous acid. DMT derivatives hydrolyze fastest, followed by MMT derivatives, and trityl derivatives slowest.
(a) Draw the product with the trityl derivative on the 5鈥� oxygen.
(b) Explain why the trityl derivative is selective for the 5鈥� OH group. Why doesn鈥檛 it react at 2鈥� or 3鈥�? (c) Why is the DMT group easiest to remove under dilute acid conditions? Why does the solution instantly turn orange when acid is added to a DMT derivative?

Short Answer

Expert verified

(a)

(b)

Trityl groups are specific for primary alcohols than secondary or tertiary alcohol, this is due to fact that size of trityl group is more, and secondary or tertiary alcohol will also create steric hindrance. Thus, trityl group is selective for 5鈥� OH group.

(c)

DMT group gets stabilised under acidic conditions, thus gets easily removed. The orange color arises from the extended conjugation through all three rings and out onto methoxy groups in DMT under acidic conditions.

Step by step solution

Step-1(a). Trityl derivative product on 5’ oxygen of nucleoside:

Trityl chloride on reaction with nucleoside and in presence of base such as triethylamine, gives the product or trityl derivative which is linked to the 5鈥� oxygen of the nucleoside. This derivative can be easily removed under dilute acidic conditions.

Trityl derivative product

Step-2(b). Selectivity of trityl derivative:

Trityl groups are specific for primary alcohols rather than secondary or tertiary alcohols. This is due to steric reasons, as trityl group itself is large and we know that secondary or tertiary alcohols also has some steric hindrance, thus, approach of secondary alcohol is restricted onto trityl derivative and reaction is very slow whereas with primary alcohol, reaction is fast. Thus, trityl group is selective for 5鈥� OH group and not for 2鈥� or 3鈥� group.

Step-3(c). Reaction of DMT group under dilute acidic conditions:

DMT group gets stabilised under dilute acid conditions due to extended resonance. Also each methoxy group stabilises the carbocation formed by resonance as depicted in resonating structures. The orange color arises from the extended conjugation which occurs in the DMT group as a result of stabilisation in acidic conditions.