Approach to the synthesis of candelabrone and synthesis of 3,7-diketo- 12-hydroxyabieta-8,11,13-triene

Abstract

992). An approach to the synthesis of aromatic diterpenes was tested for its generality. Phenylacetonitriles with increasing substitution on the aromatic ring were prepared and alkylated with geranyl bromide and the resulting dienes subjected to cationic cyclization. The less-substituted examples afforded tricyclic products of the required stereochemistry while the more highly substituted compounds cyclized with reduced yields or not at all. One of the intermediates was used to synthesize nimosone (3,7-diketo-12-methoxyabieta-8,11,13-trine) a natural diterpene isolated originally from Chamaecyparis forrnoserlsis and recently from Azadirachta indica.ROBERT H. BURNELL et STEPHANE CARON. Can. J. Chem. 70, 1446 ( 1992). Une sene de phCnylacCtonitriles substituks par une chaine gCranyle et un nombre croissant de groupements mkthoxyles a Cte soumise B des conditions de cyclisation cationique pour determiner la generalit6 de la rCaction. Seulement les substrats les moins encombrCs ont rCagis efficacement donnant les produits tricycliques de la stCrCochimie requise et un de ces derniers a semi comme intermediaire clC pour la synthese de la nimosone, une dicetone diterpenique isolCe de Chat7zaecyparis fortnosensis et plus rkcemment de Azadirachtc~ indica.In recent years more examples of aromatic diterpenes with oxygen functions in the A ring have appeared in the literature. Hypagenins A , D , and E (I), candelabrone (2) and several coleons (3) fall in this category and the neem tree, Azadirachta indica, is a rich source of these new compounds (4). Few syntheses are reported for these products since many of the schemes that start with simpler naturally occuring chiral terpenes, such as podocarpic and dehydroabietic acids (5), do not lend themselves readily to the introduction of functions into the A ring past the quaternary centres at C 4 and C10. A more total approach could be advantageous but, unlike those derived from chiral precursers, the final products from most sequences would be racemic.After first probing the application of radical cyclizations of the type described by Snider et al. (6) it was decided to test the generality of the cationic equivalent as championed by Livinghouse and co-workers (7). Ultimately we hope to apply the scheme to the synthesis of candelabrone 1 but the first objective was the simpler 3,7-diketo-12-hydroxyabieta-8,11,13-triene 2a originally isolated from Chamaecyparis formosensis (8) and more recently from Azadirachita iizdica when it was given the name nimosone (4a).This synthetic approach involves the cyclization of nonconjugated dienes such as 5 a in which half the molecule '~u t h o r to whom correspondence may be addressed.comes from the naturally derived geranyl bromide 3 and the other 10 skeletal carbon atoms are provided by substituted phenylacetonitriles, such as 4. Specifically the latter has been prepared from o-isopropylanisole 6a in an overall yield of close to 65%. Bromination of 6a by potassium bromide and m-CPBA in the presence of 18-crown-6 afforded 84% of the bromo der...

Syntheses and evaluation of multicaulin and miltirone-like compounds as antituberculosis agents

“…Following our previous procedure, compound 17 was converted to 19 by O -methylation followed by selective bromination with CAN/LiBr. Preparation of benzyl bromide 23 from compound 19 was as described by Burnell and Caron 24 . Following this procedure with a slight modification, we prepared compound 23 .…”

A Formal Total Synthesis of Salvadione

“…In a way, C has elements of strategy A and B. Our investigations started with the phenol 14, [9] obtained by oxidation of the corresponding isopropyl resorcin derivative [10] with meta-chloroperbenzoic acid (mCPBA). Etherification (CH 3 I, K 2 CO 3 ) led to the fully protected trimethoxy compound 15.…”

“…All commercially available compounds were used as received, unless stated otherwise. The aromatic compounds 2-isopropyl-1,3-dimethoxybenzene, 3-isopropyl-2,4-dimethoxyphenol (14), and 2-isopropyl-1,3,4-trimethoxybenzene (15) were prepared according to Burnell [10] from methyl 2,6-dimethoxybenzoate. 1-Bromo-3-isopropyl-2,4,5-trimethoxybenzene (16) was prepared according to Carreno et al [11] Cyclohexenone 18 was prepared according to Riesser.…”

“…To a stirred mixture of phenol [10] 14 (1.74 g, 8.87 mmol, 1.00 equiv.) and dried paraformaldehyde (0.533 g, 17.7 mmol, 2.0 equiv.)…”

Facile Access to Optically Active Ring C Aromatic Diterpenes from (+)-manool. Synthesis of (+)-13-Hydroxypodocarpa-8,11,13-Triene, (+)-7-Deoxynimbidiol and (+)-Nimbidiol

“…10 To date, a number of synthetic investigations of these biologically active podocarpane diterpenes have been reported by * Correspondent: E-mail: jvillami@ivic.gob.ve employing podocarpic acid, labdane diterpenes or via polyene cyclisation. [11][12][13][14][15][16][17] However, they generally require long reactions sequences, and furthermore, almost all of them produce the racemic form of the natural substance.…”