Flueggeacosines A–C, Dimeric Securinine-Type Alkaloid Analogues with Neuronal Differentiation Activity from Flueggea suffruticosa

Abstract

Flueggeacosines A–C (1–3), three dimeric securinine-type alkaloid analogues with unprecedented skeletons, were isolated from Flueggea suffruticosa. Compounds 1 and 2 are the first examples of C-3–C-15′ connected dimeric securinine-type alkaloids. Compound 3 is an unprecedented heterodimer of securinine-type and benzoquinolizidine alkaloids. Biosynthetic pathways for 1–3 were proposed on the basis of the coexisting alkaloid monomers as the precursors. Compound 2 exhibited significant activity in promoting neuronal differentiation of Neuro-2a cells.

Biosynthetically Inspired Syntheses of Secu′amamine A and Fluvirosaones A and B

“…[27,28] Thedioxetane moiety in 33 can then undergo ar ing opening and be transformed into the lactam and carboxylic acid moiety present in 34. [29] Notably,r ecently isolated natural product flueggeacosine B(35) [30] consists of the molecular framework of 34 and hints at the plausibility of as imilar oxidative ringcleavage event during its biosynthesis.F urthermore,t he experimentally discovered inherent chemical propensity of 32 to undergo facile air oxidation and subsequent bond scission undermined the originally proposed biosynthetic pathway of 13,apathway that involves the C2-epimer of 32 (see Scheme S1). [16] After noticing the air-sensitivity of 32,w ep lanned to intercept 31 by an in situ reduction.…”

Biosynthetically Inspired Syntheses of Secu′amamine A and Fluvirosaones A and B

“…The dioxetane moiety in 33 can then undergo a ring opening and be transformed into the lactam and carboxylic acid moiety present in 34 . Notably, recently isolated natural product flueggeacosine B ( 35 ) consists of the molecular framework of 34 and hints at the plausibility of a similar oxidative ring‐cleavage event during its biosynthesis. Furthermore, the experimentally discovered inherent chemical propensity of 32 to undergo facile air oxidation and subsequent bond scission undermined the originally proposed biosynthetic pathway of 13 , a pathway that involves the C2‐epimer of 32 (see Scheme S1) …”

Total Synthesis of (±)‐Phyllantidine: Development and Mechanistic Evaluation of a Ring Expansion for Installation of Embedded Nitrogen‐Oxygen Bonds

“…Phyllantidine possesses a unique oxazabicyclo[3.3.1]nonane structure and exhibits leishmanicidal activity and anti‐inflammatory properties . Interestingly, Flueggeacosine B ( 11 ), a heterodimer of phyllantidine ( 1 ) and a novel securinega alkaloid fragment containing a azabicyclo[3.2.1]octane system, was isolated recently in 2018 from the roots of Flueggea suffruticosa and displays potent neuronal differentiation activity …”