Biomimetic Synthesis of Psiguajdianone Guided Discovery of the Meroterpenoids from Psidium guajava

Abstract

Psiguajdianone (1), a novel caryophyllene-derived meroterpenoid dimer, was isolated from Psidium guajava. The structure of 1 was determined by X-ray analysis and confirmed by total synthesis. Our synthetic strategy involves biomimetic cascade Knoevenagel condensation/hetero-Diels−Alder reaction and dimerization. Notably, the caryophyllene-derived meroterpenoids obtained during our synthesis were first identified as artifacts in the laboratory, and five of them were proven to be natural products present in the plant. Moreover, these compounds show significant anti-inflammatory activity.

Biomimetic Synthesis Enables the Structure Revision of Littordials E and F and Drychampone B

“…Littordials A–D all feature a 6–6–9–4 ring system that could arise from a hetero-Diels–Alder reaction between an o -quinone methide ( o -QM) and the reactive trans Δ 4,5 alkene of caryophyllene. Indeed, similar cycloadditions have been achieved in the biomimetic synthesis of several caryophyllene-derived meroterpenoids . However, the proposed seven- and eight-membered rings of littordials E and F (highlighted in blue in Figure ) are biosynthetically implausible.…”

Convergent biomimetic semisynthesis of disesquiterpenoid rumphellolide J

“…(−)-β-Caryophyllene ((−)-1) can be obtained from different natural sources in large quantities and can be used not only as a cheap, renewable starting material to access more complex low-abundance natural compounds, but also to study biosynthetic connections in nature. Several natural product syntheses from (−)-β-caryophyllene have been recently demonstrated, including the biomimetic syntheses of meroterpenoids, [4][5][6][7][8] semisyntheses of rumphellaones A-C, 9 as well as the rearrangement of caryophyllene derivative to the tricyclic presilphiperfolan-1β-ol structure, 10 providing evidence for biosynthetic relationships in nature. Only few examples to date depict the applicability of β-caryophyllene and β-caryophyllene oxide in gramscale syntheses of natural products of rare occurrence.…”

Six-membered ring systems: with O and/or S atoms

“…The literature concerning the total synthesis of natural O-6-membered compounds was very rich in 2019. Thus, biomimetic and biocatalytic total synthesis of meroterpenoid bruceol (19AGE1427), biomimetic total synthesis of five meroterpenoid austalides: (AE)-17S-dihydroaustalide K, (AE)-austalide K, (AE)-13-deacetoxyaustalide I, (AE)-austalide P, and (AE)-13-deoxyaustalide Q acid (19JOC4961), biomimetic hetero-DielseAlder (hDA) reactions for the synthesis of the dihydropyran core of xenovulene A and sterhirsutins A and B (19OL998), biomimetic Knoevenagel/hDA reaction cascades for the total synthesis of chromans, (AE)-pestalachloride C, and (AE)-pestalachloride D (19OL1755), of psiguajanones AÀD and psiguajanol A and subsequent radical dimerization to obtain psiguajdianone (19OL8700), biomimetic total synthesis of isochromen furoerioaustralasine and their structure revision (19OL8776), and biomimetic synthesis of meroterpenoids, including its xanthene moiety, from dimethyl orsellinic acid and farnesyl pyrophosphate (19AGE16141), have all been accomplished.…”