Rubber is just one of many natural products that contain isoprene units joined together in a head-to-tail fashion. Non-polymeric compounds containing two or more isoprene units are called terpenes. Terpenes containing 10 carbons are called monoterpenes, those containing 20 carbons are classified as diterpenes, and those with 30 carbons are called triterpenes. The bisoynthetic precursor of terpenes and natural rubber is a 10 carbon ester called geranyl phosphate. The rest of this topic describes, in brief outline, the biosynthetic reactions involved in the formation of this compound.
The process begins with the breakdown of D-glucose, a 6-carbon sugar, into two molecules of the 3-carbon carboxylic acid pyruvic acid. Decarboxylation of pyruvic acid yields acetic acid, which is utilized as its thio ester, acetyl coenzyme A. Equation 1 illustrates this multi-step, enzyme-catalyzed transformation.
AcetylCoA serves as the building block for the synthesis of many biomolecules. In the case at hand, two molecules of acetylCoA condense to form the 4-carbon thioester acetoacetylCoA as shown in Equation 2.
This reaction is the biological equivalent of the Claisen condensation:
AcetoaceylCoA is a bifunctional molecule; it contains both a ketone group and a thioester group. Consequently, when it reacts with another molecule of acetylCoA, it may do so at either functional group. As Figure 1 indicates, attack of another molecule of acetylCoA on the thioester group, a nucleophilic acyl substitution reaction, leads to a molecule that contains a linear 6-carbon backbone. Alternatively, an acetylCoA molecule may add to the keto group to form a molecule that contains a 5-carbon backbone with a 1-carbon branch at the third carbon.
The nucleophilic addition alternative, which is reiterated in Equation 4, is the path that leads to the formation of isoprene-derived natural products.
The acid required to protonate the oxygen atom and the base required to deprotonate the acetylCoA in reaction 4 are supplied by amino acid residues in the active site of the enzyme that catalyzes the condensation.
The thioester groups in the condensation product from reaction 4 undergo hydrolysis to produce the dicarboxylic acid shown in Equation 5.
Reduction of this diacid generates the hydroxy acid, mevalonic acid, shown in Equation 6.
Phosphorylation of the two OH groups in mevalonic acid, Equation 7, produces a phosphate derivative, which is transformed into isopentenyl pyrophosphate as outlined in Equation 8.
Isopentenyl pyrophosphate isomerizes readily to g,g-dimethylallyl pyrophosphate as shown in Equation 9.
Two structural features about g,g-dimethylallyl pyrophosphate are noteworthy. First, the pyrophosphate group is a good leaving group in nucleophilic aliphatic substitution reactions. Second, when this group is attached to an allylic carbon, as it is in g,g-dimethylallyl pyrophosphate, it becomes an even better leaving group. Consequently, when a molecule of isopentenyl pyrophosphate encounters a molecule of g,g-dimethylallyl pyrophosphate, the nucleophilic aliphatic substitution reaction illustrated in Equation 10 occurs.
Note that geranyl pyrophosphate contains an allylic pyrophosphate group as well as a nucleophilic double bond. Consequently, as mentioned at the outset, it is well suited to undergo dimerization, trimerization, ..... polymerization reactions.