Efficient synthesis of 2-alkylidene-3-iminoindoles, indolo[1,2-b]isoquinolin-5-ones, delta-carbolines, and indirubines by domino and sequential reactions of functionalized nitriles.
The sodium hydride mediated cyclization of arylacetonitriles with oxalic acid bis(imidoyl) dichlorides, aza-analogues of oxalyl chloride, afforded functionalized 2-alkylidene-3-iminoindoles with very good regio- and E/Z selectivity. Excellent chemoselectivities were observed for functionalized substrates. Based on these results a domino "cyclization-lactamization" reaction of bis(imidoyl) chlorides with methyl 2-(cyanomethyl)benzoate was developed. This process allowed a convenient one-pot synthesis of indolo[1,2-b]isoquinolin-5-ones related to tryptanthrin. A new and convenient synthesis of delta-carbolines by intramolecular electrocyclization-elimination reactions of 2-alkylidene-3-iminoindoles was developed. It was shown that delta-carbolines selectively bind to triplex or duplex DNA (intercalation). Indirubine analogues were prepared by deprotection and lactonization of functionalized 2-alkylidene-3-iminoindoles.
Langer
Peter
P
Ernst-Moritz-Arndt-Universität Greifswald Institut für Chemie und Biochemie Soldmannstrasse 16, 17487 Greifswald, Germany. peter.langer@uni-greifswald.de
Anders
Joachim T
JT
Weisz
Klaus
K
Jähnchen
Judith
J
D000470:Alkaloids / Q000138:chemical synthesis* / Q000378:metabolism; D001665:Binding Sites; D002243:Carbolines / Q000138:chemical synthesis* / Q000378:metabolism; D003500:Cyclization; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000378:metabolism; D007211:Indoles / Q000138:chemical synthesis* / Q000378:metabolism; D008956:Models, Chemical; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry*; D011804:Quinolines / Q000138:chemical synthesis / Q000378:metabolism; D013237:Stereoisomerism
D000470:Alkaloids; D002243:Carbolines; D006576:Heterocyclic Compounds, 4 or More Rings; D007211:Indoles; D009570:Nitriles; D011804:Quinolines; C480966:hydroxycryptolpine; D004247:DNA; C027185:indirubin