I. The Terpene Marrubiin

Abstract

The biosynthesis of the diterpene marrubiin has been studied using some labelled possible precursors: [2-14C] mevalonate, [1-14C] acetate, [2-14C] acetate, [2-14C] pyruvate, [2,3-14C] succinate, [1,4-14C] succinate, [5-14C] ketoglutarate and [1,5-14C] citrate. Metabolism times of 24, 36, 48, 72 and 96 hours were used. The labelled compounds were supplied in solution to flowering white horehound (Marrubium vulgare L.), cut at the base of the stem. The incorporation results indicate that marrubiin undergoes a rapid turnover with a biological half life of about 24 hours. The rate of up-take of 14C from the prcursors is in the following order: [2-14C] mevalonate, [2-14C] acetate, [1-14C] acetate, [2-14C] pyruvate and [2,3-14C] succinate. Incorporation of 14C from the other compounds is negligible. If [2-14C] mevalonate is used, labelled marrubiin is formed 10 - 100 times more active than with the other precursors. The results suggest that all the precursors are degradated to acetic units through the Krebs cycle before their utilization, with the exception of mevalonate. Some samples of marrubiin (I) have been degradated chemically to the corresponding ketoderivative (II), in order to determine the distribution of radioactivity between the decahydronaphthalenic and furanic parts. The results are in good agreement with the distribution of the radioactivity in the molecule, as expected from the terpenoid structure of marrubiin.