A synthesis of acronycine

Hlubucek, J.; Ritchie, E; Taylor, WC

doi:10.1071/ch9701881

Cited by 77 publications

(37 citation statements)

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“…The synthesis of acronycine by the first strategy employed an Ullmann condensation as a key step (Loughhead, 1990) while the synthesis by the second employed a Claisen rearrangement (Hlubucek et al, 1970;Schneider et al, 1972;Ramesh and Kapil, 1986), which has been modified (Anand and Selvapalam, 1996).…”

Section: Introductionmentioning

confidence: 99%

2,2-dimethyl-2H-pyran-derived alkaloids I. Practical synthesis of acronycine and benzo[b]acronycine and their biological properties

et al. 2008

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The 2,2-dimethyl-2H-pyran-derived alkaloids acronycine and its demethylated congeners were prepared in three steps from anthranilic acid and phloroglucinol. The phenylboronic acid-mediated interamolecular cyclization reaction of 1,3-dihydroxyacridone and 3-methylbut-2-enal was employed as a key step, which was also applied to the synthesis of related cytotoxic benzo[b]acronycine. Inhibitory activities of the compounds prepared on topoisomerase I and II as well as their cytotoxicities were evaluated. Cytotoxicity of 2 is closely related to the strong inhibitory activity against topo II at 20 microM level.

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Section: Introductionmentioning

confidence: 99%

2,2-dimethyl-2H-pyran-derived alkaloids I. Practical synthesis of acronycine and benzo[b]acronycine and their biological properties

et al. 2008

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“…Catalytic osmium tetroxide oxidation of 8 and 9 using N-methylmorpholine N-oxide to regenerate the oxidative agent 20 , after a separated column, afforded the respective (+)-cis-diol sulfoxide (17) and (19) in 65 % and 80% yield respectively, accompanied by small amounts of the corresponding sulfoxides non hydroxylated on the pyran ring (16) and (18). In the angular series, a very small amount of (+)-cis-diol non-sulfoxide (20) were also obtained from the reaction mixture with the previously described reaction.…”

Section: Discussionmentioning

confidence: 99%

“…Based on previous synthetic experiments in the acronycine series 18 , the synthesis of 8 and 9 was envisioned through Claisen rearrangement of an intermediate dimethylpropargyl ether. Thus, treatment of 10H-2-hydroxyphenothiazine (10) prepared from the commercially available 10H-2-methoxyphenothiazine (11) by a demethylation using boron tribromide (1M solution in methylene chloride) with 3-chloro-3-methylbut-1-yne (12) 19 in alkaline medium afforded the required 2-(1,1-dimethylpropargyloxy)-phenothiazine (13) in 65% yield (Scheme 1).…”

Section: Discussionmentioning

confidence: 99%

Synthesis and bioevaluation of new pyranophenothiazine derivatives

Nguyen¹,

Dufat²,

Michel³

et al. 2017

Pharm Sci Asia

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Until now, tuberculosis is always a dangerous infectious disease. Because of the enlargement of multidrug-resistant strains (MDR-TB), the need of new drugs becomes more important. Fusing of 2 pharmacophores (phenothiazine and benzopyran), we intend to synthesize some new pyranophenothiazine derivatives, and evaluate their antituberculosis activities. The designed compounds were prepared using conventional synthetic methods with all PA chemical agents (from Merk, TCI, Sigma). The structure of all synthesized compounds had been confirmed by analysis of NMR and MS spectra. Antimycobacterial activity of the synthesized compounds on Mycobacterium bovis BCG (or on the virulent strain Mycobacterium tuberculosis H37Rv for the most promising compounds) had been determined using the Microdilution resazurin assay. 2 compounds 8 and 9 were obtained by Claisen rearrangement of intermediate dimethylpropargyl ether. The sulfoxide and (+)cis-diol sulfoxide derivatives were obtained by oxydation, and the dihydro-derivatives -by reduction of the leader compounds. The anti-tuberculosis activities of 12 synthesized compounds were evaluated. Only the leading compound of linear structure (pyrano[b]phenothiazine) and 2 non-sulfoxide derivatives of angular structure (pyrano[a]phenothiazine) exhibited a mild inhibiting activity on the tested tuberculosis source. 12 new pyrano-phenothiazine compounds have been prepared and bioevaluated. The results showed that 3 compounds exhibited a mild inhibiting activity on the tested tuberculosis source. These structural requirements will be taken into account for the design of further analogues in pyranophenothiazine series.

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“…The strategy employed to synthesize benzo[b]acronycine (43) was essentially similar to that previously developed by Hlubucek et al for the synthesis of acronycine itself (Hlubucek et al 1970). Condensation of 3-amino-2-naphthalenecarboxylic acid (53) (Costes et al 2000).…”

Section: Benzo[a] [B] and [C]acronycine Derivativesmentioning

confidence: 99%

Rutaceous alkaloids as models for the design of novel antitumor drugs

Tillequin

2007

Phytochem Rev

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The chemical diversity of alkaloids in the Rutaceae is correlated with biosynthetic pathways involving various aromatic amino acid precursors, tyrosine, tryptophan, histidine, and anthranilic acid. The interest of rutaceous polyheteroaromatic alkaloids as models for the development of anticancer agents relies on their frequent ability to interact with DNA or with systems involved in the control of its topology, repair, and replication. Fagaronine and nitidine, from Zanthoxylum, demonstrate antileukemic activity, associated with topoisomerases inhibition. Evodiamine from Euodia rutaecarpa, displays antimetastatic properties. The pyranoacridone acronycine, from Sarcomelicope, exhibits antitumor activity against a broad spectrum of solid tumors. Development of synthetic analogues based on this latter natural product template followed the isolation of the unstable acronycine epoxide, which led to a hypothesis of bioactivation of acronycine by transformation of the 1,2-double bond into the corresponding oxirane. 1,2-Diacyloxy-1,2-dihydroacronycine derivatives exhibited antitumor properties, with a broadened F. Tillequin (

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A synthesis of acronycine

Abstract: Improved syntheses of certain O-and N-methyl derivatives of 1,3-dihydroxy-acridone are described. Thermal rearrangement of the appropriate 3-α,α-dimethyl-propargyl ethers in the series yields products which may be methylated to acronycine.

Cited by 77 publications

References 0 publications

2,2-dimethyl-2H-pyran-derived alkaloids I. Practical synthesis of acronycine and benzo[b]acronycine and their biological properties

2,2-dimethyl-2H-pyran-derived alkaloids I. Practical synthesis of acronycine and benzo[b]acronycine and their biological properties

Synthesis and bioevaluation of new pyranophenothiazine derivatives

Rutaceous alkaloids as models for the design of novel antitumor drugs

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