TY - JOUR

T1 - Short Approach to Pyrrolopyrazino-, Pyrrolodiazepino-Isoindoles and their Benzo Analogues via the IMDAF Reaction

AU - Zubkov, Fedor I.

AU - Orlova, Daria N.

AU - Zaytsev, Vladimir P.

AU - Voronov, Alexander A.

AU - Nikitina, Eugeniya V.

AU - Khrustalev, Victor N.

AU - Novikov, Roman A.

AU - Krasavin, Mikhail

AU - Varlamov, Alexey V.

PY - 2017

Y1 - 2017

N2 - 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 alpha,beta-unsaturated acid anhydrides (maleic and citraconic 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-epoxy-pyrrolo[ 2', 1': 3,4][1,4] diazepino[2,1-a] isoindoles, tetrahydro-14bH-12,14a-epoxyisoindolo[2,1-a] pyrrolo[2,1-c] qui-noxalines, 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.

AB - 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 alpha,beta-unsaturated acid anhydrides (maleic and citraconic 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-epoxy-pyrrolo[ 2', 1': 3,4][1,4] diazepino[2,1-a] isoindoles, tetrahydro-14bH-12,14a-epoxyisoindolo[2,1-a] pyrrolo[2,1-c] qui-noxalines, 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.

KW - Furans

KW - Diels-Alder reaction

KW - cycloaddition

KW - domino reaction

KW - pyrrolopyrazine

KW - pyrrolodiazepine

KW - IMDAF reaction

KW - RECEPTOR ANTAGONISTS

KW - OPTIMIZATION

KW - INHIBITORS

KW - SCAFFOLDS

KW - DISCOVERY

KW - PYRROLE

KW - DIVERSE

KW - ROUTE

U2 - 10.2174/1570179414666161116123221

DO - 10.2174/1570179414666161116123221

M3 - статья

VL - 14

SP - 733

EP - 746

JO - Current Organic Synthesis

JF - Current Organic Synthesis

SN - 1570-1794

IS - 5

ER -