The synthesis of 1 -methyl- and 1α,2α-methylene-gibberellins

Abstract

The syntheses of 1α-methyl-, 1β-methyl-, and 1α,2α-methylene-gibberellins required for further investigations into structure–biological activity relationships are described. Thermolysis of the pyrazoline derived from GA₇-3-ketone-7-methyl ester gave, as the major product, the corresponding 1 -methyl enone with minor amounts of the 1α,2α-methyleneGA₄-3-ketone-7-methyl ester. The latter compound was reduced and hydrolysed to 1α,2α-methyleneGA₄. Reduction of the 1 -methyl enone with sodium borohydride gave 1α-methylGA₄methyl ester, which was hydrolysed to 1α-methylGA₄, and 1α-methyl-3-epi-GA₄, methyl ester which was deoxygenated to give 1α-methylG₉. The palladium-catalysed reduction of the 1-methyl enone gave 1β-methylGA₄-3-ketone and 1α-methylGA₄-3-ketone which were converted into the corresponding 1β-methylGA₄ and 1α-methylGA₄. The analogous synthesis of the C-l alkylated 13-hydroxylated gibberellins was improved by the use of a phenacyl ester to protect C-7, thus providing routes to 1β-methylGA₁, 1α-methylGA₁, and 1α,2α-methyleneGA₁.

Incubation of 1α-methylGA₄ with the fungus Gibberella fujikuroi, mutant B1 -41a, gave 1α-methyl-GA₁, as the sole metabolite. Incubation of 1β-methylGA₄ with the mutant B1 -41 a gave 1 -methylGA₃, 1-methylGA₇, and 1β-methylGA₁ confirming that it is the 1α-hydrogen which is lost in the 1,2-didehydrogenation process in the fungus.