Cyclotryptophan Mycotoxins: Short Synthesis of the Desymmetrized meso-Chimonantine Core of Leptosin C

Abstract

The desymmetrized meso-chimonantine core of leptosin C was prepared in a short stereoselective convergent sequence in 5 steps as the longest linear path from methyl L-tryptophan hydrochloride as starting material. The key step of this approach was a diastereoselective [4+2] cycloaddition between the bromooxindole and tryptophan derivatives allowing to define the adjacent quaternary benzylic centers in a high chemical yield.

Catalytic Enantioselective Alkylation of Aldehydes with 3-Bromooxindoles

“…As these methodologies provide facile access to the C3 quaternary carbon center of oxindoles, development of variant asymmetric reactions would be of high synthetic value. In this respect, a wide array of nucleophiles, such as malonates, oximes, carboxylic acids, indolines, 3-substituted indoles and oxindoles, β-naphthols, silyl ketene imines, and anilines, have been found to be competent in this type of stereoablative addition reaction or tandem processes, many of which have been elegantly applied in total syntheses of indole alkaloids. , Despite these breakthroughs, the carbonyl nucleophiles, however, were generally limited to activated compounds like malonates, β-ketoacids, or trifluoromethyl α-fluorinated β-keto- gem -diols (Scheme a) . Even though the incorporation of an aldehyde partner would generate valuable enantioenriched adducts given the versatile downstream conversions of the aldehyde functionality, such an addition reaction has received less study, with only two elegant examples regarding α-alkylation of limited aldehydes with 3-hydroxy-3-indolylox-indoles …”