New oxidized ent-kaurane and ent-norkaurane derivatives from kaurenoic acid

Abstract

Novos derivados oxidados ent-caurânicos e ent-norcaurânicos foram sintetizados a partir do ácido caurenóico. Todos os produtos obtidos foram caracterizados espectroscopicamente.New oxidized ent-kaurane and ent-norkaurane derivatives were synthezised starting from kaurenoic acid. The spectroscopic characterization of all compounds is reported. Keywords: diterpenes, kaurenoic acid, ent-kaurane and ent-norkaurane derivatives, PDC oxidation IntroductionKauranes are an important class of diterpenes containing a rigid tetracyclic skeleton and exhibiting a wide variety of biological activities such as antitumor, anti-HIV, trypanocidal and antimicrobial, among others. 1 For this reason, the development of new strategies for the synthesis of novel kaurane derivatives may be considered as one of the interesting challenges in Chemistry of Natural Products. Indeed, many naturally occurring bioactive kauranes have been transformed using chemical and microbial methods in order to improve their bioactivity. 2,3 Kaurenoic acid (ent-kaur-16-en-19-oic acid, 1) is an intermediate in the biosynthesis of numerous plants and fungal secondary metabolites, including gibberellins, the phytohormones involved in the regulation of growth and development of higher plants, 1 found abundantly in some Brazilian species as Wedelia paludosa D.C. (Asteraceae), Xylopia frutescens and Annona glabra (Annonaceae). 4 We have reported, in a previous phytochemical study of Wedelia paludosa D.C., the isolation of kaurenoic acid (1) as the main ent-kaurane diterpene in this species, besides other related diterpenes and triterpenes as minor constituents. -17-hydroxykauran-19-oate (6). The nomenclature and numbering of ent-kaurane derivatives obtained in this work follow the IUPAC recomendations. 13 Results and DiscussionKaurenoic acid (1), isolated from aerial parts of Wedelia paludosa D.C., 4,5 was esterified with diazomethane to the corresponding methyl ester 2, which was subjected to two different pathways of chemical transformation (Scheme 1). 623 Batista et al. Vol. 18, No. 3, 2007 The first one was the epoxidation of 2 with MCPBA taking place stereoselectively at the more accesible side of the double bond, to yield exclusively the ent-16β,17-epoxide 3, what was confirmed by X-ray crystallography.14 Further rearrangement of 3 employing Lewis acids such as InCl 3 or BF 3 afforded a 1:1 mixture of epimer aldehydes 4 and 5, in moderate to quantitative yields (43% and 100%, respectively), that could not be separated by column chromatography. A mixture of products is usually obtained from rearrangement of epoxides to carbonyl compounds, due to lack of regioselectivity in the ring opening step. 15Moreover, methyl ester 2 was subjected to hydroboration reaction with NaBH 4 and BF 3 •Et 2 O, followed by NaOH and H 2 O 2 oxidation, giving exclusively the hydroxymethyl group at the ent-α side of the derivative 6. These results, affording stereoselectively the alcohol 6 with an ent-16α configuration, are in agreement with literature data 16 and are justifi...

Diterpenoids of Alepidea Amatymbica Eckl. & Zeyh: Studies of Their Cytotoxic, Antimicrobial, and Lipoxygenase Inhibitory Activities

“…Subsequently, eluted with different polarity of acetone-ethyl acetate solvent system. The fractions were collected from the column, purified by PTLC to give five compounds (1) (60mg), (2) (62.1mg), (3) (52mg), (4) (108mg), and (5) (62mg) from F [8][9][10][11][12][13][14][15][16][17][18][19] (100mg), F 75-87 (87mg), F 52-64 (80mg), F 20-28 (310mg), and F [35][36][37][38][39][40][41][42][43][44][45] (74mg), respectively.…”

Evaluation of ent-Kaurenoic Acid Derivatives for their Anticariogenic Activity

“…(methyl ent-kaur-16(17)-en-19-oate, 160.0 mg)[15]. To a solution of 1 (50.0 mg; 0.165 mmol) in MeOH (2 mL) was added two drops of concentrated H 2 SO 4 , the mixture stirred at 25 o C for 18 h, poured into water (20 mL) and extracted with ethyl acetate (3 x 20 mL).…”

Wagner-Meerwein rearrangement of steviol 16α,17- and 15α,16-epoxides

“…When boron trifluoride-diethyl ether complex BF 3 · Et 2 O is used as Lewis acid, fluorohydrins [17], unsaturated alcohols, or dienes [18] may be formed, depending on the substrate structure and reaction conditions. As concerns epoxy derivatives of the ent-kaurane series, steviol 15α,16-epoxide methyl ester (V) in the presence of WCl 6 underwent rearrangement into 14α-hydroxyisosteviol (VII) having ent-beyerane structure [6] (Scheme 2), while ent-kaurane 16α,17-epoxide IX in the presence of BF 3 · Et 2 O gave rise to aldehyde X with ent-kaurane structure [19] (Scheme 4). We found that the direction of the latter reaction strongly depends on the presence (or absence) of a hydroxy group on C 13 .…”