Oxidative dearomatic approach towards the synthesis of erythrina skeleton: a formal synthesis of demethoxyerythratidinone

Abstract

A concise synthetic route leading to highly functional erythrina alkaloid skeletons has been developed. The key process is an oxidative carbon-carbon coupling followed by a conjugated addition. Based on this new strategy, a formal synthesis of demethoxyerythratidinone was completed in only 6 steps from 4-aminophenol.

Clean Synthetic Strategies to Biologically Active Molecules from Lignin: A Green Path to Drug Discovery**

“…For example, the secondary amines 3 b′ and 3 k′ are known precursors in the synthesis of orexin receptor antagonists, [28] used to treat sleep disorders, as well as isoalloxazine derivatives, [29] agents for the treatment of Alzheimer's disease. Potentially, 3 q′ can serve as a key building block for the synthesis of medicinally relevant erythrina alkaloids [30,31] . In our hands, the synthesized aminoalkyl guaiacols have shown various biological activities, as shown in Figure 2A and summarized in Supporting Information in Section 11.…”

Clean synthetic strategies to dopamine-based biologically active molecules from lignin: A green path to drug discovery

“…For example, the secondary amines 3bʹ and 3kʹ are precursors in the synthesis of orexin receptor antagonists (35), which are used to treat sleep disorders, as well as isoalloxazine derivatives (36), agents for treatment of Alzheimer's disease. Potentially, 3qʹ can serve as a key building block for the synthesis of erythrina alkaloids (37,38), that possess sedative, hypotensive, and CNS activities. In addition, 3q could be used as a building block for the synthesis of bio-based polymers (39).…”

A stereospecific total synthesis of dl-hexahydroapoerysopine

“…162–163 °C) was prepared according to the protocol developed by Zhang et al in a good yield from the readily accessible aromatic precursor 6 . 3 The stereostructure of 3 was verified as shown by single crystal X-ray diffraction analysis (Scheme 1). 8 Exposure of spirocyclic enone 3 to an excess of trifluoromethanesulfonic acid (TfOH) in CH 2 Cl 2 at room temperature effected a clean and stereospecific skeletal rearrangement to give crystalline enone 7 in 91% yield (m.p.…”

“…1a and b). We report herein the further extension of this rearrangement approach on the readily accessible Erythrinane derivative 3 3 leading to an efficient and stereospecific synthesis of dl -hexahydroapoerysopine ( 4 ) bearing the all- cis ring fused stereostructure and a phenolic apoerysopine derivative 5 , a structurally intriguing and historically important Apo rearrangement product of the aromatic Erythrina alkaloids. Pioneering studies by Prelog and co-workers in the 1950s on the Apo rearrangement not only established the skeletal structure of the Erythrina alkaloids I , but also revealed the general tendency of this type of skeletal rearrangement via a postulated cationic intermediate II for the Erythrina family alkaloids.…”

“…2, an assumingly facile skeletal rearrangement approach via the Prelog's Apo intermediate II has not appeared since the original documentation of the Apo rearrangement of Erythrina alkaloids. A recent report by Zhang and co-workers 3 on an excellent approach to Erythrinane derivative 3 via an efficient oxidative annulation prompted us to explore the straight Apo rearrangement method to hexahydroapoerysopine ( 4 ) in a stereospecific manner.…”