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Short Approach to Pyrrolopyrazino-, Pyrrolodiazepino-Isoindoles and their Benzo Analogues via the IMDAF Reaction

[ Vol. 14 , Issue. 5 ]

Author(s):

Fedor I. Zubkov*, Daria N. Orlova, Vladimir P. Zaytsev, Alexander A. Voronov, Eugeniya V. Nikitina, Victor N. Khrustalev, Roman A. Novikov, Mikhail Krasavin and Alexey V. Varlamov   Pages 733 - 746 ( 14 )

Abstract:


Aim and Objective: A new approach to synthesis of isoindoles condensed with other heterocycles and revelation of their spatial structure for biochemistry purposes was the main objective of this research.

Material and Method: Starting materials for the proposed method, 1-furyl substituted pyrrolo[1,2-a]pyrazines, pyrrolo[1,2-a][1,4]diazepines and their benzoannulated analogues - 4-furyl substituted pyrrolo[1,2-a]quinoxalines and pyrrolo[1,2-a][1,4]benzodiazepines, were synthesized by known procedures. These compounds, all containing a furfurylamine moiety, were introduced into the tandem acylation/ intramolecular furan Diels-Alder (IMDAF) reaction with α,β-unsaturated acid anhydrides (maleic and itraconic anhydrides). In most cases, the key step – the IMDAF reaction – proceeds diastereospecifically with simultaneous formation of five new stereogenic centers and affording the title compounds in mild conditions with satisfactory overall yields.

Results: Consequently a broad series of 10,12a-epoxypyrrolo[2’,1’:3,4]pyrazino[2,1-a]isoindoles, 11,13a-epoxypyrrolo[ 2’,1’:3,4][1,4]diazepino[2,1-a]isoindoles, tetrahydro-14bH-12,14a-epoxyisoindolo[2,1-a]pyrrolo[2,1-c]quinoxalines, and tetrahydro-9H,15bH-13,15a-epoxyisoindolo[1,2-c]pyrrolo[1,2-a][1,4]benzodiazepines was synthesized and their space structure was elucidated by X-ray analysis.

Conclusion: New effective method for synthesis of isoindoles condensed with various heterocycles was proposed. The method is based on the IMDAF reaction and provided a broad diversity of target molecules with controlled stereochemistry.

Keywords:

Furans, Diels-Alder reaction, cycloaddition, domino reaction, pyrrolopyrazine, pyrrolodiazepine, IMDAF reaction.

Affiliation:

Organic Chemistry Department, Faculty of Science, RUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Organic Chemistry Department, Faculty of Science, RUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Organic Chemistry Department, Faculty of Science, RUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Organic Chemistry Department, Faculty of Science, RUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Organic Chemistry Department, Faculty of Science, RUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Inorganic Chemistry Department, Faculty of Science, RUDN University, 6 Miklukho-Maklaya St., Moscow 117198, V. A. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov St., Moscow, Department of Chemistry, St. Petersburg State University, Peterhof 198504, Organic Chemistry Department, Faculty of Science, RUDN University, 6 Miklukho-Maklaya St., Moscow 117198

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