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Four naturally occurring analogues of forskolin were isolated. Forty-nine semisynthetic derivatives were prepared, incorporating structural alterations at the 1-, 6-, 7-, 9-, 11-, and 14/15-positions. Blood pressure lowering properties of 53 compounds were assessed in anesthetized normotensive cats and of 31 compounds in conscious spontaneously hypertensive (SH) rats. The positive inotropic properties of 25 compounds were investigated in an isolated guinea pig atrial preparation. Forskolin was unique among the compounds in its hypotensive activity in cats and in its positive inotropic properties. Although several derivatives displayed oral antihypertensive activity in the SH rats, none was significantly more potent than forskolin. The optimal structural requirements for activity are apparent, since they are found in forskolin itself.

Plants belonging to the Coleus and Plectranthus genera of the Labiatae were semi-quantitatively assayed for the presence of forskolin, a potent cardioactive and hypotensive diterpenoid under development. In the T L C and G L C assay methods employed, forskolin could be detected at levels down to ca. 1 x % of the dry plant material. Coleus forskohlii BRIQ. appears to be unique in that it is the only species among those assayed which was found to contain forskolin.

Forskolin (1 ) (7P-acetoxy-8,13-epoxy-l a,6fJ,9a-trihydroxylabd-l4-en-11 -one), the major diterpenoid of Coleus forskohlii, has potent positive inotropic, antihypertensive, and adenylate cyclase stimulant properties. The reactivity of its various functional groups (1 a-OH, 6P-OH, the derived 7P-OH, 9a-OH, 11 -oxo, and 14,15-double bond) has been studied through acylation, alkylation, dehydration, oxidation, and reduction reactions. Pharmaceuticals Limited, Bombay -400 080, India

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