Sesquiterpenoids of Warburgia species—II : Ugandensolide and ugandensidial (cinnamodial)

doi:10.1016/0040-4020(69)80031-1

Tetrahedron

Volume 25, Issue 14, 1969, Pages 2887-2898

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Abstract

Two crystalline sesquiterpenoids of drimane type, ugandensolide (I) and ugandensidial (II) have been isolated from the heartwood of Warburgia ugandensis Sprague (Canellaceae), and their structures determined. Ugandensidial proved to be identical with cinnamodial from Cinnamosma fragrans Baillon (Canellaceae). An interesting example of isomerization during GLC has been observed for the α-acetoxy-ketones (VII and XIV).

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Cited by (55)

Bioactive drimane sesquiterpenoids and aromatic glycosides from Cinnamosma fragrans
2017, Bioorganic and Medicinal Chemistry Letters
Phytochemical investigation of the ethyl acetate and methanol extracts of the bark of Madagascan endemic and medicinal plant Cinnamosma fragrans led to the isolation of two drimane sesquiterpene derivatives: cinnafragroside A (1) and cinnafragrin E (2), two aromatic glycosides: 3,4,5-trimethoxyphenol 1-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (3) and 3,4-dimethoxyphenyl-1-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (4), together with 12 known compounds identified as: helicide (6), 1-(α-l-rhamnosyl(1→6)-β-d-glucopyranosyloxy)-3,4,5-trimethoxybenzene (7), vanilloloside (8), cinnamadin (9), ugandensolide (10), cinnamosmolide (11), cinnamolide (12), polygodial (13), cinnamodial (14), bemadienolide (15), 4-isopropyl-6-methyl-α-tetralone (16), and capsicodendrin (17). Another new compound, 11-norcinnafragrolide-9-one (5), was obtained during chemical derivatization of capsicodendrin and gave a hint to understanding the structure required for the antiproliferative activity of 17. The structures of the new compounds were elucidated based on the interpretation of their spectroscopic data including one and two dimensional nuclear magnetic resonance (1D- and 2D-NMR) and mass spectroscopic data. All isolated compounds were evaluated against the hormone dependent breast cancer cell line MCF-7. Compound 17 exhibited the most potent activity with an IC₅₀ value of 0.6 μM. Our preliminary SAR study showed that the hydroxyl group at C-12′ and the presence of conjugated carbonyl contribute to the antiproliferative activity.
Warburgia: A comprehensive review of the botany, traditional uses and phytochemistry
2015, Journal of Ethnopharmacology
Citation Excerpt :
The fragrant heartwood of W. ugandensis prompted Glasgow researchers, Brooks and Draffan (1969a), to explore the phytochemistry of the species resulting in the isolation of the first two novel sesquiterpenoids, warburgin (47) and warburgiadione (12), as well as drimenol (13). They later went on to isolate ugandensolide (34) and ugandesidial (11), the latter which they reported to be synonymous with cinnamodial from Cinnamosma fragrans Baillon (Brooks and Draffen, 1969b) (Fig. 3). The use of the stem bark as a spice in east African cooking resulted in the fragrant, often pungent, compounds being explored further.
The genus Warburgia (Canellaceae) is represented by several medicinal trees found exclusively on the African continent. Traditionally, extracts and products produced from Warburgia species are regarded as important natural African antibiotics and have been used extensively as part of traditional healing practices for the treatment of fungal, bacterial and protozoal infections in both humans and animals. We here aim to collate and review the fragmented information on the ethnobotany, phytochemistry and biological activities of ethnomedicinally important Warburgia species and present recommendations for future research.
Peer-reviewed articles using “Warburgia” as search term (“all fields”) were retrieved from Scopus, ScienceDirect, SciFinder and Google Scholar with no specific time frame set for the search. In addition, various books were consulted that contained botanical and ethnopharmacological information.
The ethnopharmacology, phytochemistry and biological activity of Warburgia are reviewed. Most of the biological activities are attributed to the drimane sesquiterpenoids, including polygodial, warburganal, muzigadial, mukaadial and ugandensial, flavonoids and miscellaneous compounds present in the various species. In addition to anti-infective properties, Warburgia extracts are also used to treat a wide range of ailments, including stomach aches, fever and headaches, which may also be a manifestation of infections. The need to record anecdotal evidence is emphasised and conservation efforts are highlighted to contribute to the protection and preservation of one of Africa׳s most coveted botanical resources.
Sesquiterpenes from the Medicinal Plants of Africa
2013, Medicinal Plant Research in Africa: Pharmacology and Chemistry
Sesquiterpenes are C15-terpenoids built from three isoprene units. They are found particularly in higher plants and in many other living systems such as marine organisms and fungi. Naturally, they occur as hydrocarbons or in oxygenated forms including lactones, alcohols, acids, aldehydes, and ketones. Sesquiterpenes also include essential oils and aromatic constituents with several pharmacological activities. This chapter summarizes the basic skeletons and nomenclature as well as the general biosynthetic pathway of sesquiterpenes. Some examples of this class of secondary metabolite as potential lead compounds in pharmaceutical and other applications are also provided. The challenge in this chapter is the assessment of the sesquiterpenes reported from African medicinal plants to date. We identify herein up to 421 sesquiterpenes, including 322 compounds isolated for the first time and 99 known derivatives reported from plants collected in Africa as well as their pharmacological activities. From the results it is clear that closer collaboration between phytochemists and disciplines such as pharmacology, microbiology, and parasitology could lead to the development of useful products based on the valuable biological activity of sesquiterpenoids.
7α-Acetylugandensolide and antimicrobial properties of Warburgia ugandensis extracts and isolates against sweet potato pathogens
2011, Phytochemistry Letters
Citation Excerpt :
The IR spectrum showed the presence of an ester carbonyl (1732 cm−1), γ-lactone carbonyl (1680 cm−1) and olefinic bond (1632 cm−1). In the 1H NMR spectrum, the resonances of three quaternary methyls (δ 1.03, 1.05 and 1.51, each singlet), two oxymethine protons (δ 5.54 br s, J = 1.7 Hz and 5.15, br d, J = 1.3 Hz, H-7) and oxymethylene protons (δ 4.71, dd, J = 17.8, 1.1 Hz and 4.61, d, J = 17.7 Hz) could be ascribed to a drimane skeleton (Brooks and Draffan, 1969; Kioy et al., 1990). The 1H NMR spectral features of 1 closely resembled those of ugandensolide (Brooks and Draffan, 1969) except for an additional acetyl group signal evidenced by a peak at δH 2.13 with corresponding 13C NMR peaks centered at δC 169.8 and 20.8.
7α-Acetylugandensolide together with thirteen known drimane-type sesquiterpenes have been isolated from Warbugia ugandensis bark extracts. Their structures were established by spectroscopic and physical methods as well as comparison with data available in the literature. The in vitro antimicrobial activities of the extracts and isolates were investigated against fungi and bacteria which infect sweet potato. Ethyl acetate extract exhibited the highest (P ≤ 0.05) antifungal and antibacterial activities compared to n-hexane and methanol extracts. Rhizopus stolonifer was more susceptible to ethyl acetate extract (inhibition zone = 24.5 mm) than Blitox which was used as a positive control. The minimum inhibitory concentration (MIC) for the isolates ranged between 12.5 and 200 μg/ml with the lowest MIC value of 12.5 μg/ml being observed with polygodial against Fusarium solani; warburganal against Aspergillus niger and F. solani; and mukaadial against A. niger.
Inhibition of mycobacterial arylamine N-acetyltransferase contributes to anti-mycobacterial activity of Warburgia salutaris
2007, Bioorganic and Medicinal Chemistry
In this study, we show that extracts and a purified compound of Warburgia salutaris exhibit anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv and Mycobacterium bovis BCG Pasteur. The extracts did not inhibit growth of Escherichia coli and were not toxic to cultured mammalian macrophage cells at the concentrations at which anti-mycobacterial activity was observed. The extract and pure compound inhibited pure recombinant arylamine N-acetyltransferase (NAT), an enzyme involved in mycobacterial cell wall lipid synthesis. Moreover, neither extract nor pure compound inhibited growth of a strain of M. bovis BCG in which nat has been deleted suggesting that NAT may indeed be a target within the mycobacterial cell. The purified compound is a novel drimane sesquiterpenoid lactone, 11α-hydroxycinnamosmolide. These studies show that W. salutaris is a useful source of anti-tubercular compounds for further analysis and supports the hypothesis of a link between NAT inhibition and anti-mycobacterial activity.
Synthetic investigations in the field of drimane sesquiterpenoids
2006, Studies in Natural Products Chemistry
In this article, the results of the author’s investigations in the field of the synthesis of drimane sesquiterpenoids, a group of terpenic compounds which possess a wide variety of biological activities (antifeedant, antibacterial, antifungal, anticomplemental, cytotoxic, antiallergic, piscicidal, molluscicidal, plant growth regulatory, insecticidal and others) have been reviewed. The original structural- and stereoselective methods for obtaining natural compounds in the optically-active form, and also of important intermediates on the pathway to them, including alcohols, poliols, ketones, lactones and acids, have been elaborated. Most of the compounds obtained are polyfunctional. Much attention has been focussed on the synthesis of drimenol, a drimanic sesquiterpene key compound, which is widely used as a starting substance in syntheses of many biologically active drimanes. Much effort has been devoted to elaborate the syntheses of drim-8-en-7-one and drim-5,8-diene-7-one, compounds possessing a great synthetic potential. Indeed, using those above a large number of natural compounds, such as isodrimenin, 7-oxoisodrimenin, 7-oxo-5,6-dehydroisodrimenin, trans-tetrahydroactinidiolide and intermediates for the syntheses of polygodial and warburganal, compounds with various and high biological activities, were prepared.

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Sesquiterpenoids of Warburgia species—II : Ugandensolide and ugandensidial (cinnamodial)

Abstract

Tetrahedron

Aust. J. Chem.

J. Am. Chem. Soc.

J. Chem. Soc.

J. Chem. Soc.

J. Chem. Soc.

Chem. Commun.

J. Am. Chem. Soc.

Tetrahedron Letters