Bis-spirolabdane Diterpenoids from Leonotis nepetaefolia

Leonotis nepetaefolia R. Br. (family: Lamiaceae, syn. Labiatae), also known as Klip Dagga or Lion's Ear, is widely distributed throughout tropical Africa, southern India, and the tropical regions of America. It is traditionally used in Caribbean folk medicine and Ayurvedic herbal medicine to treat a wide array of human diseases such as coughs, fever, stomachache, skin infections, rheumatism, dysmenorrhea, and kidney dysfunction.1–4 In Mexico, the name “mota”(marijuana) is given for this plant, which suggests that L. nepetaefolia is used as a marijuana substitute.5 In addition, a variety of biological activities including antispasmodic,5 antibacterial, antifungal,6,7 anti-inflammatory,8 antioxidative,9,10 antiasthmatic, and antidiarrheal11 activities have been reported for the crude extracts or pure compounds from this plant. Previous phytochemical studies of the plant indicated the presence of labdane diterpenoids,2,4,12–17 iridoids,9,10 and coumarins.18 As part of an ongoing effort to search for bioactive constituents from psychoactive plants, the lipid extract of the leaves of L. nepetaefolia was investigated. This procedure led to the isolation of ten new bis-spirolabdane diterpenoids, named leonepetaefolins A–E (1, 3, 5, 7, 9) and 15-epi-leonepetaefolins A–E (2, 4, 6, 8, 10), together with eight known labdane diterpenoids including methoxynepataefolin (11),13,16,19 nepetaefolin (12),12,15,20 nepetaefuran (13),12 dubiin (14),21 compound 15,12 leonotinin (16),14,20 leonotin (17),20 and LS-1 (18),22 and two known flavonoids apigenin23 and cirsiliol.24 Herein, we describe the isolation and structural elucidation of the ten new bis-spirolabdane diterpenoids 1–10.