Chapter 20, Problem 57DSP

Thioesters

Thioesters have the general formula . They resemble their oxygen counterparts

(oxoesters) in structure and reactivity more than other carboxylic acid derivatives such as acyl

chlorides, acid anhydrides, and amides. Thioesters can be prepared from thiols by reaction with acyl chlorides or acid anhydrides in much the same way as oxoesters are prepared from

alcohols.

The preparation of thioesters by Fischer esterification is not very effective, however, because

the equilibrium is normally unfavorable. Under conditions in which ethanol is converted to ethyl

benzoate to the extent of $\text{68\%}$, ethanethiol gives only $\text{15\%}$ ethyl thiobenzoate.

This, and numerous other observations, indicates that $\text{S-C=O}$ is less stabilized than $\text{O-C=O}$.

Like chlorine, sulfur is a third-row element and does not act as an electron-pair donor to the carbonyl group as well as oxygen.

Thioesters and oxoesters are similar in their rates of nucleophilic acyl substitution, except with

amine nucleophiles for which thioesters are much more reactive. Many biological reactions involve nucleophilic acyl substitutions referred to as acyl transfer reactions. The thioester acetyl coenzyme A is an acetyl group donor to alcohols, amines, and assorted other biological nucleophiles.

Melatonin, a hormone secreted by the pineal gland that regulates circadian rhythms, including wake–sleep cycles, is biosynthesized by a process in which the first step is an enzyme-catalyzed transfer of the acetyl group from sulfur of acetyl coenzyme A to the ${\text{-NH}}_{\text{2}}$ group of serotonin.

Acetylcholine is a neurotransmitter formed in nerve cells by the enzyme-catalyzed reaction

of choline with acetyl coenzyme A.

What is the most reasonable structure for choline?