金催化炔烃环异构化反应

article info
Article history: Received 5 September 2012 Revised 11 October 2012 Accepted 16 October 2012 Available online 23 October 2012
Keywords: Pentacyclic pyrido[4,3,2-mn]acridin-8-one Domino reaction Gold catalysis 6-endo-dig Cycloisomerization N-Propargylaminoquinone
abstract
A novel methodology taking advantage of a domino reaction initiated by an Au(I)-catalyzed 6-endo-dig cycloisomerization under silver-free condition was developed to prepare pentacyclic pyrido[4,3,2mn]acridin-8-ones from N-propargylaminoquinones. Triphenylphosphinegold(I) chloride in combination with TFA was firstly employed and displayed excellent catalytic efficiency in the domino reaction.
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8H-Pyrido[4,3,2-mn]acridin-8-one is a basic skeleton embedded in marine alkaloids isolated from sponges and ascidians.1 These alkaloids have attracted considerable attention because of their significant cytotoxicity.2 The isolated pentacyclic pyrido[4,3,2mn]acridin-8-one alkaloids (amphimedine,3 neoamphimedine,4,5 meridine,6 isocystodamine,7,8 and ecionine A9) feature fused pyridone, pyridine, or tetrahydropyridine heterocycle at C9, 10 position of the pyridoacridine ring system and display certain specific biological activities such as inhibition of topoisomerase II and induction of neuronal differentiation (Fig. 1). The pronounced biological properties make them to be potential drug candidates for the treatment of cancers. However, the scarcity of the alkaloids has hampered further biological evaluations. Efforts to obtain pentacyclic pyrido[4,3,2-mn]acridin-8-one alkaloids as well as relevant analogs by means of chemical synthesis still remain in urgent need.10
N
N O 8H -Pyrido[4,3,2-mn]acrid-8-one
N O
N H3C
N O
Amphimedine
N
N
H3C
N
OO
Neoamphimedine
OH N
N N
HN N
N
N
O
Meridine
N NH2 O
Isocystodamine
N O NH
Ecionine A
Figure 1. Pentacyclic pyrido[4,3,2-mn]acridin-8-one alkaloids.
Hao Yin, Fanji Kong, Shaozhong Wang ⇑, Zhu-Jun Yao
School of Chemistry and Chemical Engineering, State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, PR China
o-nitro or o-trifluoroacetamidocinnamaldehyde-N,N-dimethylhydrazone as diene to synthesize meridine and cystodamine, even though the yield of the hetero-Diels–Alder cycloaddition from the 1-azadiene was low and side products involving dihydroanthraquinone and regioisomer of the desired adduct were accompanied seriously.
Assembly of pentacyclic pyrido[4,3,2-mn]acridin-8-ones via a domino reaction initiated by Au(I)-catalyzed 6-endo-dig cycloisomerization of N-propargylaminoquinones
Tetrahedron Letters 53 (2012) 7078–7082
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Tetrahedron Letters
journal homepage: /locate/tetlet
The classic strategy to assemble pentacyclic pyrido[4,3,2mn]acridin-8-one skeleton is closely associated with the construction of tricyclic diazaanthraquinone. Always, 4-arylated 1,6-, 1,8-, and 1,9-diazaanthraquinones were elaborated as straightforward precursors of pyrido[4,3,2-mn]acridin-8-ones, and the final formation of pyridine ring was established by an intramolecular reductive cyclization or hydrolytic cyclization from the diazaanthraquinone (Scheme 1). Conventionally, the 4-arylated diazaanthraquinone
Aiming at discovering new methodology to construct pentacyclic pyrido[4,3,2-mn]acridin-8-one heterocycles, we envisioned a domino reaction initiated by Au(I)-catalyzed 6-endo-dig cycloisomerization of N-propargylaminoquinone,16 which is distinct from the stepwise methodology based on hetero-Diels–Alder cycloaddition. As outlined in Scheme 2, N-propargylaminoquinone containing free aniline functionality attached on alkyne terminus was designed as the substrate. Under the gold catalysis,17 two possible reaction pathways should take place in principle. The activated triple bond would be attacked either by the enamine moiety of aminoquinone in a 6-endo manner (pathway a) or by the amine in a 5-endo manner (pathway b). The former cycloisomerization will definitely afford the tricyclic 4-(2-aminophenyl)-azaanthraquinone, which might be spontaneously converted into pentacyclic pyrido[4,3,2-mn]acridin-8-one by an intramolecular condensation between carbonyl of quinone and aniline group.