Coleus forskohlii (WILLD.) BRIQ. (Labiatae) has been used for medical treatment in Hindu and Ayurvedic traditional medicine from ancient times. 1) Since its major constituent forskolin was discovered to have positive inotropic, antihypertensive, and adenylatecyclase-stimulating activities, it has ever aroused a great deal of scientific interest, and many 8,13-epoxy-labd-14-en-11-one diterpenes have been obtained.1-11) The plant was subsequently found in Yunnan Province of China, while the major diterpene was determined to be coleonol B.10,11) So as to discover more novel and active compounds, further examination of the polar fraction of the whole plant extract has been carried out and yielded two new diterpene glycosides and a sesquiterpene in our earlier research.12) Continuing work yielded three other new diterpene glycosides forskoditerpenosides C, D, and E (1-3) and a diterpene forskoditerpene A (4). Complete NMR data studies on each compound were performed unambiguously to determine the structures of the compounds and to assign all the proton and carbon resonances. The isolation and structural elucidation of them are reported below. Forskoditerpenosides C, D, and E (1-3) were tested for their effects on isolated guinea pig tracheal spirals in vitro. Results and DiscussionAir-dried whole plants of C. forskohlii were extracted with EtOH three times. The concentrated extract was dissolved in water and successively extracted with petroleum ether (60-90°C) and n-BuOH. The n-BuOH soluble fraction was extracted with H 2 O in reflux and the combined solution was separated by means of various chromatographic procedures to afford four labdane diterpenes (1-4). . According to these spectral data, 1 was considered to be a 8,13-epoxy-labd-14-en-11-one diterpene. [1][2][3][4][5][8][9][10][11] The 1 H-NMR signal at d 5.71 (1H, dd, Jϭ4.0, 2.4 Hz) was assigned to H-6 by its coupling constants. 13,14) The chemical shifts of H-6 and C-6 suggested that Pharmacy, Meijo University; Tempaku, Nagoya 468-8503, Japan. Received August 6, 2007; accepted September 25, 2007 Three new minor labdane diterpene glycosides, forskoditerpenoside C, D, and E (1-3), and a novel labdane diterpene forskoditerpene A (4) were isolated from the ethanol extract of the whole plant of Coleus forskohlii. Their structures and relative stereochemistry were elucidated on the basis of extensive spectroscopic analyses including 1D-, 2D-NMR, and HR-ESI-MS experiments. Compounds 1-3 showed an unusual 8,13-epoxy-labd-14-en-11-one glycoside pattern. They showed relaxative effects on isolated guinea pig tracheal spirals in vitro. Compound 4 with a cyclopropyl, confirmed by a single-crystal X-ray diffraction determination, is the first known labdane derivative with a spiro element.

Coleus forskohlii (WILLD.) BRIQ. (Labiatae) is largely distributed over the tropical and subtropical regions of India, Pakistan, Sri Lanka, tropical East Africa and Brazil, and it has been used since ancient times for medical treatment in Hindu and Ayurvedic traditional medicine.1,2) Its characteristic constituents, 8,13-epoxy-labd-14-en-11-one diterpenes, especially the main constituent forskolin, showed positive inotropic, antihypertensive and adenylatecyclase stimulating activities.2-12) The plant was later found in Yunnan Province of China and its aqueous extract has been used as a natural medicine to cure asthma, cough, acute and chronic bronchitis. [10][11][12] Up to now, almost the whole studies have been concentrated on these lipophilic labdane diterpene aglycones, and only two previous studies reported the polar fraction of the whole plant extract, from which only caffeic acid and two monoterpene glycosides were obtained. 13,14) In order to discover more novel and active compounds, further examination of the polar fraction has yielded two new diterpene glycosides, forskoditerpenosides A, B (1, 2) and a new eudesmane sesquiterpene, 4b,7b,11-enantioeudesmantriol (3), whose structures were established on the basis of 1D, 2D NMR and HR-ESI-MS. The relative configuration of 3 was further confirmed by single-crystal X-ray diffraction. Their isolation and structural elucidation are reported below. Compounds 1 and 2 were tested for effect on isolated guinea pig tracheal spirals in vitro. Results and DiscussionThe 95% EtOH extract of the whole plant of C. forskohlii afforded compounds 1-3, which were identified as 6b-acetoxy-7b,9a-dihydroxy-8,13-epoxy-labd-14-en-11-one-1a-Ob-D-glucopyranoside (1), 6b,7b-diacetoxy-9a-hydroxy-8,13-epoxy-labd-14-en-11-one-1a-O-b-D-glucopyranoside (2), and 4b,7b,11-enantioeudesmantriol (3).Forskoditerpenoside A (1) . These spectral data were consistent with the characteristics for 8,13-epoxy-labd-14-en-11-one type diterpenes. 8-12)The 1 H-NMR signal at d 5.74 (1H, dd, Jϭ2.8, 4.8 Hz) was assigned to H-6 by its coupling constants. 15,16) The chemical shifts of H-6 and C-6 suggested that an acetyl group was attached to C-6, as confirmed by the cross-peak between d H 5.74 and d C 171.2 in the HMBC spectrum (Fig. 2). Then, the signals at d 2.39 (1H, d, Jϭ2.8 Hz) and 4.28 (1H, d, Jϭ4.8 Hz) were assigned to H-5 and H-7, respectively, interpreted from their coupling constants as well as HMQC and HMBC correlations.15) The signal at d 4.33 (1H, br s), which showed long-range correlations with C-2, C-3, C-5, C-10 and C-20 in the HMBC spectrum, was attributed to H-1, correlated to C-1 at d 86.5 in HMQC spectrum. According to the above analysis, the structure of 1 was very similar to that of coleonol B isolated from this plant earlier, in exception of a signal for an anomeric proton at d 4.21 (1H, d, Jϭ7.8 Hz), linked to the anomeric carbon at d 106.0 in its HMQC spectrum, as well as five oxygenated carbons between d 63.7 and 79.0 and six proton signals between d 3.17 and 3.81. Combining the Mo...

In the mol­ecule of the title compound (systematic name: 1α‐hydr­oxy‐6β,7β‐diacet­oxy‐8,13‐epoxy­labd‐14‐en‐11‐one), C24H36O7, rings A and B adopt chair conformations, while ring C has a twist–boat conformation. The crystal structure is stabilized by inter­molecular O—H⋯O and C—H⋯O hydrogen bonds, linking the mol­ecules into networks approximately parallel to the (110) plane.

Terpenes U 0200 Two Minor Diterpene Glycosides (I) and an Eudesmane Sesquiterpene (II) from Coleus forskohlii. -Forskoditerpenoside A (Ia) and B (Ib) show relaxative effects on isolated guinea pig tracheal spirals in vitro. -(SHAN, Y.; WANG, X.; ZHOU, X.; KONG*, L.; NIWA, M.; Chem.