Section 17.20 Synthesis of Carboxylic Acid Derivatives 7133-D Molecule:
Adenosine triphosphateCarboxylic acids can also be activated for nucleophilic acyl substitution reactions
by being converted into anhydrides. Treating a carboxylic acid with a strong dehydrat-
ing agent such as yields an anhydride.
Carboxylic acids and carboxylic acid derivatives can also be prepared by methods
other than nucleophilic acyl substitution reactions. A summary of the methods used to
synthesize these compounds is given in Appendix IV.
Activation of Carboxylate Ions for Nucleophilic Acyl Substitution
Reactions in Biological Systems
The synthesis of compounds by biological organisms is called biosynthesis. Acyl
halides and acid anhydrides are too reactive to be used as reagents in biological sys-
tems. Cells live in a predominantly aqueous environment, and acyl halides and acid
anhydrides are rapidly hydrolyzed in water. So living organisms must activate car-
boxylic acids in a different way.
One way living organisms activate carboxylic acids is to convert them into acyl
phosphates, acyl pyrophosphates, and acyl adenylates.
An acyl phosphateis a mixed anhydride of a carboxylic acid and phosphoric acid; an
acyl pyrophosphateis a mixed anhydride of a carboxylic acid and pyrophosphoric
acid; an acyl adenylateis a mixed anhydride of a carboxylic acid and adenosine
monophosphate (AMP).
The structure of adenosine triphosphate (ATP) is shown below with “Ad”in place of
the adenosyl group; adenosine monophosphate has two fewer phosphate groups.
Acyl phosphates are formed by nucleophilic attack of a carboxylate ion on the
g-phosphorus (the terminal phosphorus) of ATP. Attack of a nucleophile on the P“O
OHO OH−OOOOO
O−POO−POO−P
−OOOOO−PO−P
OOAd
O−PNH 2
NN NN=adenosine triphosphate
ATPphosphoric acidHOOOHP
OHOOHP
HO OHOOHP
Opyrophosphoric acidan acyl phosphate an acyl pyrophosphate an acyl adenylateROOOCO−P
O− ROOO −C
R OO OCOAd
O−POO−POO−PCOCOCOOH P 2 O (^5) O
2
P 2 O 5