Spirocyclization reactions and antiproliferative activity of indole phytoalexins 1-methoxybrassinin and its 1-substituted derivatives

Abstract

The effect of the reaction temperature and the solvent on the diastereoselectivity of the spirocyclization of 1-methoxybrassinin leading to 1-methoxyspirobrassinol methyl ether was studied. 1-Acyl derivatives of 1-methoxyspirobrassinol and 1-methoxyspirobrassinol methyl ether were prepared by the bromine-mediated spirocyclization reactions of derivatives of brassinin bearing an acyl group on the indole nitrogen with water or methanol as nucleophilic agents. The cyclization of 1-acyl derivatives of brassinin afforded the trans-diastereoisomer as the major product, whereas using 1-methoxybrassinin afforded the cis-and trans-isomers in a ratio near to 1:1. Bromospirocyclization of brassinin and 1-methylbrassinin in the presence of methanol resulted in the formation of spirobrassinin and 1-methylspirobrassinin. The newly synthesized analogues of indole phytoalexins exhibited more significant antiproliferative activity against human leukemia cell lines than the natural phytoalexins.

Mechanochemical Synthesis and Isomerization of N-Substituted Indole-3-carboxaldehyde Oximes †

“…It seems that the isomerization process is accompanied by deacetylation in this case. The relevant literature reports used sodium acetate as a base and either higher temperature [54] or longer time [53] was necessary for the reaction completion.…”

“…1-Methylindole-3-carboxaldehyde was prepared according to the procedure reported in [77]. 1-Acetylindole-3-carboxaldehyde was prepared according to the procedure reported in [53].…”

“…There are many reports on the solution-based syntheses of N -substituted indole-3-carboxaldehyde oximes from their aldehydes [49,50,51,52,53,54]. Regarding the 1-methoxy analog, Hanley et al firstly reported the conversion of the corresponding aldehyde to oxime with the 50% yield [55].…”