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. Total synthesis The first total synthesis of torreyanic acid was reported by Porco an co-workers in 2000. This total synthesis aimed to employ and confirm the Diels–Alder genesis proposed by Lee et al. To synthesize the monomers required for Diels–Alder dimerization, 1,3-dioxane intermediate 4 was lithiated with BuLi, brominated with BrCF2CF2Br, and underwent acid hydrolysis to afford benzaldehyde 5. Upon selective methylation of 5 with sulfuric acid, phenol 6 was produced in 52% yield. Phenol 6 first underwent an allylation with allyl bromide, then a borohydride reduction, and finally a protection with a silyl group to furnish 7. Dimethoxyacetal 8 was furnished upon thermal Claisen rearrangement of 7, which afforded an unstable allyl phenol that directly underwent a hypervalent iodine oxidation with in methanol. 8 was then subjected to an acetal exchange with 1,3-propanediol to afford 1,3-dioxane 9, which was smoothly monoepoxidized with Ph3COOH, KHMDS, −78 °C to −20 °C over 6 hours to afford 10. A 2-methyl-2-butenoic acid moiety was installed to afford 11. Intermediate 11 underwent a Stille vinylation with (E)-tributyl-1-heptenyl stannane, subsequently subjected to TBAF/AcOH for silyl removal and acetal hydrolysis to afford quinone epoxide 12. Treatment of 12 with Dess-Martin periodinane initiated a tandem oxidation-6p-electrocyclization-dimerization to afford two dimeric products 13 and 14. Upon treatment of 13 and 14 with TFA to remove the tert-butyl ester, iso-torreyanic acid 15 and torreyanic acid 1 were afforded, respectively. References Quinones Total synthesis Epoxides Carboxylic