Reactions of Indole Derivatives with Oxiranes and Aziridines on Silica. Synthesis of β-Carbolin-1-one Mimic of Pancratistatin

Abstract

[reaction: see text] Indole and several indoles functionalized at C-2 were condensed with oxiranes, vinyloxiranes, aziridines, and vinylaziridines in the solid state on the surface of silica. The yields of these reactions were compared to those obtained from Lewis acid-catalyzed ring-opening reactions performed in solution and found to be superior in each case. The solid-phase aziridine opening constituted a key step in the synthesis of the beta-carbolin-1-one mimic of pancratistatin. Methyl 2-indolecarboxylate was found to react on the silica gel surface with N-tosylvinylaziridine in 68% yield. A nine-step synthesis of the pancratistatin mimic has been attained. The additional key transformation in this synthesis involved silica gel-catalyzed opening of an epoxide and hydrolysis of an acetonide. Detailed experimental procedures and full characterization are reported for all new compounds.

Catalytic Functionalization of Indoles in a New Dimension

“…After the preliminary studies in the 1960s and 1970s on the use of stoichiometric amounts of Lewis acids such as AlCl 3 , SnCl 4 , and BF 3 ,119 the discovery over the last decade of unusual Lewis acids such as lanthanide triflates120a and indium(III) salts120b–d opened up access to the catalytic ring‐opening of epoxides with indoles. Moreover, high pressures120e and silica gel120f were found to assist the regioselective C3‐alkylation of indoles with both racemic and enantiomerically pure epoxides.…”

Chapter 3 Chemical and Biological Aspects of Narcissus Alkaloids

“…addition of indoles to oxiranes and aziridines derived from cyclohexadiene diols) (255)(256)(257)(258). Analogues of narciclasine (68), pan crastistatin, and 7-deoxypancratistatin have been synthesized using modifications of the reported procedures as well as new methodologies (e.g.…”

Total Syntheses of Pancratistatin. A Review

“…The interesting bioisosteric replacement of the methylenedioxybenzene ring with the indole moiety as in compound 2 , also prepared by Hudlicky and coworkers, leads to essentially complete loss of in vitro anticancer activity. 29,30 …”