The
Diels-Alder reaction was named from German chemists Otto Diels and Kurt
Alder. It is an organic chemical
mechanism in which a conjugated diene and a dienophile form a substituted
cyclohexane ring. In these reactions,
three pi bonds break and two sigma bonds and one pi bond forms.
General
examples
1,
3-diene dienophile
It has
recently been found that there are enzymes that mediate the Diels-Alder
reaction in secondary metabolic biosynthetic pathways. One class of natural products that are
believed to exhibit this are polyketides.
These are derived from acetate which makes them well-suited for
experiments because they are readily available and relatively cheap. Because of this, a big part of the
experimental evidence of Diels-Alder reaction in nature is derived from this
class.
The
polyketide that has been given the most significant attention is lovastatin (chemical
structure shown below) because it is a potent inhibitor of cholesterol
biosynthesis in humans.
1 Lovastatin structure
Chemists
have speculated that the enzymes involved in the biosynthesis of lovastatin
(11) are similar to those involved in the biosynthesis of fatty acids.[9] They
proposed that condensation of acetate units could produce a triene (12) that
would undergo an endo-selective Diels–Alder cycloadditon to the decalin (13).2
2 Synthesis of the declan (14) through an in
vitro Diels-Alder cyclization of triene (15)
In the image
above, product 14a is the endo Diels-Alder product while 14d is the exo
products. The reaction mechanism shown
took place in the presence of toluene as well as with an acid catalyst. Under the thermal conditions (with toluene)
the endo to exo products were in a 1:1 ratio.
These
products were in a 19:1 endo-exo ratio under the conditions of a Lewis acid
catalyst. There was an absence of 14a in the laboratory cyclization which suggests
that the Diels-Alder cyclization in the biogenesis of lovastin could be
enzymatic.
Sources
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