Regioselective ether cleavages of rotenoids: spiro-ether formation and stereoselective isotopic labelling of (E)- or (Z)-prenyl methyl groups in (6aS, 12aS)-rot-2′-enonic acid

Abstract

Treated with boron tribromide (–)-(6aS,12aS,5′R)-rotenone is converted first into a primary allylic bromide by ring-E cleavage, then into the 2-de-O-methyl and finally the 2,3-dide-O-methyl derivatives. With (6aS,12aS,5′R)-6′7′-dihydrorotenone and (6aS,12aS)-isorotenone, ring-E cleavage does not take place. The main reaction is 2-, followed by 2,3-demethylation: this supports a stereospecific pericyclic mechanism for the rotenone ring-E cleavage. Treatment of the geometrically pure (E)-bromide with cyanoboro-deuteride or -tritide leads to (E)-4′-labelled (6aS,12aS)-rot-2′-enonic acid without reduction of the 12-carbonyl group. By using [7′-¹³C or -¹⁴C]-rotenone, (E)-[4′-¹³C- or -¹⁴C-]rot-2′-enonic acid is accessible. Trimethylsilyl iodide can cleave the 2-methoxygroup of rotenone without rupturing ring E, and remethylation with [²H]- or [³H]-diazomethane represents a convenient method for preparing a general tracer molecule.

On treatment with sodium hydride, 3-de-O-methylisorotenone (but not the 2-isomer) rearranges into a spiroether, thus confirming the position of initial de-O-methylation as deduced from ¹H and ¹³C n.m.r, data. Because of this rearrangement, methylenation (NaH–CH₂I₂) of 2,3-dide-O-methylisorotenone gives mainly the methylenedioxy-spiro-ether, with small yields of methylenedioxy-rotenoid.

Deuteriogenolysis of (–)-rotenone over palladium catalyst in (²H₅)pyridine gives (E)-[4′-²H]rot-2′-enonic acid, but experiments using [7′-¹³C]rotenone indicate stereoselectivity rather than stereospecificity, ca. 12% of (Z)-[5′-¹³C]- accompanying the major (E)-product. A similar specimen of [4′-¹⁴C]rotenonic acid has been prepared. A hydrogenolysis route from amorphigenin, via[8′-²H]rotenone, to (Z)-[5′-²H]rot-2′-enonic acid is described.