There are over 150 natural products that are presumed to undergo a [4+2] Diels–Alder type cycloaddition, belonging to classes such as: polyketides, terpenoids, phenylpropanoids, and alkaloids.  The Diels–Alder cycloaddition involves the overlap of the p-orbitals of two unsaturated systems:  a 1,3-diene and dienophile.  The conjugated diene reacts with the dienophile to form a cyclic product in a concerted fashion.  This reaction is widely used in synthesis due to its facile nature and reio- and stereoselectivity under mild conditions.  This reaction is very useful for forming carbon-carbon bonds, four-chiral centers, and quaternary stereogenic centers.[4,5]  Natural products that are constructed biosynthetically via a Diels–Alder reaction occur both uncatalyzed and catalyzed by enzymes such as Diels–Alderase and RNA Diels-Alderase.  In their report of the isolation and structural characterization of the natural product, Lee and co-worker proposed that the biosynthesis of torreyanic acid proceeded via an endo-selective [4+2] cycloaddition with a Diels–Alder dimerization of 2H-pyran monomers 2a and 2b.  Key observations that indicate a natural product is biosynthesized via a Diels–Alder reaction include:  (a) isolation of an adduct with its corresponding precursor, (b) presence of adducts and their regio- and diastereoisomers, (c) a non-enzymatic feasibility of a likely cycloaddition and (d) chirality of the adducts.
The proposed biosynthetic pathway is thought to involve:  (a) an electrocyclic ring closure of 3, followed by (b) an enzymatic oxidation to furnish diastereomers 2a and 2b, and finally (c) a [4+2] cyclodimerization to generate torreyanic acid 1.  The biosynthesis of torreyanic acid was studied extensively by Poroco et al. in their efforts to execute the first total synthesis of the natural product.  Given that monomer ambuic acid was also isolated from the same endophytic fungus Pestalotiopsis microspora, it is further evidence that a Diels–Alder reaction is involved in the biosynthesis of torreyanic acid.  The biomimetic synthesis of torreyanic acid involved the rapid conversion of aldehyde 3 to syn- and anti-pyrans 2a and 2b via an oxaelectrocyclization, with the pyrans existising as an equilibrium mixture.  Next, a spontaneous Diels–Alder dimerization of 2a and 2b proceeded with complete and regio- and diastereoselectivity to furnish the endo-adduct, torreyanic acid 1.  Further, a retro-Diels–Alder reaction carried out at 60 °C proved that torreyanic acid originated from 2a and 2b and ¹H-NMR spectra showed that no aldehyde 3 was observed.  The stable transition state in the Diels–Alder reaction (shown with 2a and 2b) has an energy of 9.4kcal/mol, and coupled with the high reactivity of the diastereomers, it is indicated that the Diels–Alder reaction proceeds in a non-enzymatic manner.