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. 2018 Aug 31;8(54):30761-30776.
doi: 10.1039/c8ra06676k. eCollection 2018 Aug 30.

Total synthesis of kealiiquinone: the regio-controlled strategy for accessing its 1-methyl-4-arylbenzimidazolone core

Velayudham Ramadoss  1 , Angel J Alonso-Castro  2 , Nimsi Campos-Xolalpa  3 , Rafael Ortiz-Alvarado  4 , Berenice Yahuaca-Juárez  4 , César R Solorio-Alvarado  1
Affiliations

Total synthesis of kealiiquinone: the regio-controlled strategy for accessing its 1-methyl-4-arylbenzimidazolone core

Velayudham Ramadoss et al. RSC Adv. .

Abstract

A practical, concise and straightforward total synthesis of kealiiquinone 1, a naphtho[2,3-d]imidazole alkaloid obtained from the Micronesian marine sponge Leucetta sp. was accomplished. The squaric acid chemistry to construct the 1,4-quinoid ring and the regioselective N-methylation through a benzo[c][1,2,5]selenadiazolium heterocycle are the key features in this report. The full details of the representative approaches involving the different attempted synthetic strategies are also presented. Finally a successful total synthesis of this complex secondary metabolite is described.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Representative imidazole alkaloids isolated from the Leucetta sp. sponge.
Scheme 1
Scheme 1. Described total synthesis of kealiiquinone to date.
Scheme 2
Scheme 2. First strategy towards the total synthesis of kealiiquinone 1.
Scheme 3
Scheme 3. Synthesis of benzimidazolones 4 and 5 for preparing 9.
Scheme 4
Scheme 4. Second strategy towards the total synthesis of kealiiquinone 1.
Scheme 5
Scheme 5. Synthesis of the regio-differentiated arylbenzimidazolone 20.
Scheme 6
Scheme 6. Attempts to synthesize the aniline 23a and benzimidazolone 26.
Scheme 7
Scheme 7. Successful retrosynthetic analysis of the kealiiquinone 1.
Scheme 8
Scheme 8. Synthetic route for accessing to the 1-methyl-4-arylbenzimidazolone 21 of the kealiiquinone.
Scheme 9
Scheme 9. Completion of the total synthesis of kealiiquinone 1.
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