Bisannulation of 2,3‐Dichloro‐1,4‐naphthoquinone with o‐Nitrophenylacetic Acid Derivatives: A Succinct Synthesis of the ABCD Ring System of Alpkinidine

Abstract

Three bisannulation strategies have been used to rapidly construct pentacyclic benzo‐fused pyrrolo[4,3,2‐mn]acridines, similar to several biologically active natural products. The key steps involve Michael substitution of 2,3‐dichloro‐1,4‐naphthoquinone with o‐nitrophenylacetic acid derivatives, followed by domino amino‐Michael substitutions/cyclisations. The most efficient of these syntheses provided a model compound (1) including the ABCD ring‐system of alpkinidine, in just three steps and 55 % overall yield.

Ethynylbenzenoid metabolites of Antrodia camphorata: synthesis and inhibition of TNF expression

“…The failure of these reactions, despite the close precedents cited above, including the double addition reaction of lithium TMS-acetylide in our own hands (21 + 22 → 23, Scheme 6), led us to hypothesise that the electron-rich benzene ring of 33 was somehow negatively impacting the outcome. Indeed, application of the most promising conditions to phenylacetylene (37) gave an approximately 1 : 1 ratio of the diastereomeric diols 38 and 39 in reasonable yield (Scheme 10), matching the result reported previously. 22 We are unable to explain why the analogous reaction of 33 fails.…”

A Concise Approach for the Synthesis of the ABCD Ring System of Alpkinidine

“…The 14 a on deprotonation gave 5 in 45% yields. The structure of 5 was confirmed by comparing with the reported data …”

“…In literature, two successful routes for the synthesis of 5 which contains ABCD ring structure present in alpkinidine are reported by Piggott et al . in 2013 by bisannulation of 2,3‐dichloro‐1,4‐naphthoquinone with o ‐nitrophenylacetic acid derivative in good yield and with oxindole derivative in poor yield (Scheme ).…”

Synthetic and Biological Utility of 2,3-Dichloro-1,4-Naphthoquinone: A Review

“…264) in water as well as in ethanol. However, reaction with indolin-2-one (268) in DMF has been explored for the synthesis of 271; scheme 56 [98]. While further reaction of 2,3-dichloro-1,4-naphthoquinone (1) and 257 with phenolic derivatives (305) produced benzofuroquinolinediones (306) in 24-31% yields using Na or KOH as base; Scheme 63 [109,110].…”

“…Scheme 22: Synthesis of benzophenazinediones (92), α, ω-bis(quinonyl)amine (99) and bis (3chloro-1,4-dinaphtho quinone) (100 Reaction of 2,3-dichloro-1,4-naphthoquinone (1) with α,ω-diamino derivatives of polyalkenylenoxides (98) resulted in the synthesis of α,ω-bis(quinonyl)amine (99) [50] and reaction with 1,4-diazepane produced 2,2-(1,4-Diazacycloheptane-1,4-diyl)-bis(3-chloro-1,4dinaphthoquinone) (100) [51]; Scheme 22.…”