Total Syntheses of (±)-Rhodonoids A and B and C12-epi-Rhodonoid B

Abstract

Total syntheses of (±)-rhodonoids A and B and C12-epi-rhodonoid B are described here. A unified strategy employed in these syntheses is an intramolecular oxa-[3 + 3] annulation for accessing the chromene unit. A Fe(OTf)-promoted diastereoselective cationic [2 + 2] cycloaddition and a photochemical [2 + 2] cycloaddition were featured to construct the cyclobutane core of (±)-rhodonoids A and B and C12-epi-rhodonoid B, respectively. Fe(OTf) also leads to an interesting bridged tetracycle, which was unambiguously confirmed by single crystal X-ray analysis.

Total Syntheses of (±)-Rhodonoids C, D, E, F, and G and Ranhuadujuanine B

“…Our total syntheses of (±)-rhodonoids E and F (Scheme ) commenced with chromene 12 , which was readily prepared from (2 E ,6 E )-farnesol via oxa-[3 + 3] annulation followed by cationic [2 + 2] cycloaddition. , Silylation using TBDPSCl to protect the phenol hydroxyl group provided 18 smoothly. Compound 18 was converted into a mixture of diastereomers 19 and 20 by oxidation with m -CPBA in CH 2 Cl 2 followed by refluxing with aluminum isopropoxide in toluene.…”

“…In an alternative biogenetic pathway (path b), hydration of the double bond of chromene 9 would give (±)-rhodonoid G via acid-catalyzed cyclization. The cyclobutane core 12 of (±)-rhodonoids E and F is similar to that of C12- epi -rhodonoid B, an analogue recently synthesized by our group . In this work, 12 was efficiently prepared through an oxa-[3 + 3] annulation and a subsequent diastereoselective cationic [2 + 2] annulation that is biosynthetic in origin .…”

“…Our long-standing interests in oxa-[3 + 3] annulation , and the biomimetic total synthesis of meroterpenoids − led us to synthesize (±)-rhodonoids C–G. In particular, annulations of resorcinols with vinyliminium salts would lead to facile construction of the chromene nucleus via a sequence of a Knoevenagel-type condensation and a six-π-electron electrocyclic ring closure (Scheme ).…”

“…In particular, annulations of resorcinols with vinyliminium salts would lead to facile construction of the chromene nucleus via a sequence of a Knoevenagel-type condensation and a six-π-electron electrocyclic ring closure (Scheme ). Biosynthetically, as shown in Scheme , we envisioned that (±)-rhodonoids C, D, and G could be derived from chromene 9 , which could be prepared via our oxa-[3 + 3] annulation. , Oxidation of chromene 9 led to epoxide 11 , which could provide (±)-rhodonoids C and D through catalysis with acid (path a). In an alternative biogenetic pathway (path b), hydration of the double bond of chromene 9 would give (±)-rhodonoid G via acid-catalyzed cyclization.…”

Biomimetic Total Synthesis of Rhodonoids C and D, and Murrayakonine D

“…This implies that the biosynthesis of 1 and 2 possibly occurs via predisposed, nonenzymatic cyclizations, which we intended to investigate further using biomimetic synthesis. The biosynthetically related rhodonoids A ( 4 ) and B ( 5 ) have also been isolated from Rhododendron capitatum and were recently synthesized by Tang et al…”