Total Synthesis of Rhodonoids A, B, E, and F, Enabled by Singlet Oxygen Ene Reactions

Abstract

Singlet oxygen is a versatile reagent for the selective oxidation of organic compounds under mild reaction conditions. It is frequently invoked in biosynthetic pathways, so it is especially suitable for application in the biomimetic synthesis of natural products. Herein, we show that use of the singlet oxygen ene reaction, combined with [2 + 2] cycloadditions, leads to concise, divergent, and redox-economic total syntheses of several polycyclic members of the rhodonoid family of meroterpenoids.

Bisaspochalasins A–C: Three Cytochalasan Homodimers with Highly Fused Ring System from an Endophytic Aspergillus flavipes

“…Bisaspochalasin C ( 3 ) may be a synthetic artifact of 2 , as trace amounts of 3 were observed in a failed attempt to cultivate single crystals of 2 in a medium of CH 2 Cl 2 /MeOH 1:1 (SI, Figures S4, S37, S38). The mechanism associated with the transformation from 2 to 3 (Scheme , black solid arrows) is proposed to proceed via a Schenck-ene photooxygenation. − …”

Biomimetic Total Synthesis of the Rubiginosin Meroterpenoids

“…Among the various possible scaffolds, the 6–6–6–4 ring system (Figure a) is comparatively rare. The simplest natural product with this structure is the meromonoterpenoid rhodonoid A ( 1 ), isolated from Rhododendron capitatum . The first merosesquiterpenoid with a 6–6–6–4 ring system to be reported was rubiginosin G ( 2 , although this natural product was originally unnamed and its relative configuration was not fully determined), isolated from Rhododendron adamsii .…”

“…The 6–6–5–4 meroterpenoid ring system (Figure b) is far more common in plant natural products, including the well-known cannabicyclol class of phytocannabinoids, and it can be synthesized via biomimetic, intramolecular [2 + 2] cycloadditions under photochemical, thermal, or acidic conditions and the merosesquiterpenoids fastinoid B ( 8 ) and rhodonoid B ( 9 ) . Given the coisolation of these 6–6–5–4 meroterpenoids alongside closely related 6–6–6–4 meroterpenoids and simpler chromene natural products such as daurichromenic acid ( 10 ), a unified biosynthesis can be proposed involving an alkene isomerization as the key point of divergence (Scheme ).…”

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

“…In 2020, Burchill and George reported a 0.5 g-scale ene-reaction with singlet oxygen and a cromene derivative, thus giving a conjugated enone after a Kornblum-DeLaMare rearrangement (Scheme 39) [89]. Further photochemical [2 + 2] cycloaddition Scheme 37: Continuous endoperoxidation of conjugated dienes and subsequent rearrangements leading to oxidized products.…”