A stereocontrolled total synthesis of methyl (±)-O-methylpodocarpate

Ling T., Chowdhury C., Kramer B.A., Vong B.G., Palladino M.A., Theodorakis E.A.

An enantioselective synthesis of the potent antiinflammatory agent (-)-acanthoic acid (1) is described. The successful strategy departs from (-)-Wieland-Miescher ketone (10), which is readily available in both enantiomeric forms and constitutes the starting point toward a fully functionalized AB ring system of 1. Conditions were developed for a regioselective double alkylation at the C4 center of the A ring, which produced compound 32 as a single stereoisomer. Construction of the C ring of 1 was accomplished via a Diels-Alder reaction between sulfur-containing diene 43 and methacrolein (36), which after desulfurization and further functionalization yielded synthetic acanthoic acid. The described synthesis confirms the proposed stereochemistry of the natural product and represents a fully stereocontrolled entry into an underexplored class of biologically active diterpenes.

Hao X., Node M., Fuji K.

Burnell R.H., Jean M., Marceau S.

A synthesis of maytenoquinone (11) from natural podocarpic acid (1) is described.

Parish E.J., Miles D.H.

As a class, octahydrophenanthrene lactones, podolactones , and related podocarpic acid derivatives have been reported to possess a wide variety of biological activities, including antileukemic activity, inhibition of plant cell growth, and hormonal and anti-inflammatory properties. In the present study, a series of synthetic intermediates derived from podocarpic acid have been prepared and evaluated with respect to their ability to inhibit human epidermoid carcinoma of the nasopharynx in vitro. The significant cytotoxicity demonstrated by methyl 6 alpha-bromo-7-oxo-O- methylpodocarpate (50% inhibition of cells at 8.85 X 10(-9) M) was markedly higher than that of the other derivatives examined. Further evaluation against L1210 and P388 lymphoid leukemias in mice failed to demonstrate significant antitumor activity.

Cava M.P., Ahmed Z., Benfaremo N., Murphy R.A., O'malley G.J.

The commercially available dye intermediates 1-hydroxyanthraquinone, 1-amino-2-methylanthraquinone and 1,8-dihydroxyanthraquinone (chrysazin) have been elaborated in a regiospecific manner into tetracyclic ketonitriles. The latter are potential precursors of the anthracycline aglycone aklavinone and its 4-deoxy analog 1

Matsumoto T., Endo Y., Okimoto M.

Reduction of abieta-8,11,13,-trien-6-one with lithium aluminium hydride, followed by treatment with lead tetraacetate and iodine, affored 6β,20-epoxyabieta-8,11,13-triene. This was converted into a separable mixture of abieta-8,11,13-trien-20-ol (13) and 5βH-abieta-8,11,13-trien-20-ol (14) by a series of reactions; ether cleavage with acetic p-toluenesulfonic anhydride, catalytic hydrogenation, and reduction with lithium aluminium hydride. Acetylation of 13 and 14 gave the corresponding acetates, 20-acetoxyabieta-8,11,13-triene (11) and 20-acetoxy-5βH-abieta-8,11,13-triene (12). Friedel-Crafts acylation of 11 with acetyl chloride in the presence of anhydrous aluminium chloride afforded 20-acetoxy-12-acetylabieta-8,11,13-triene, which was converted into pisiferol by oxidation with m-chloroperbenzoic acid and subsequent treatment with lithium aluminium hydride. The synthetic pisiferol was oxidized with Jones reagent to give pisiferal. Similarly, 5βH-abieta-8,11,13-triene-12,20-diol was synthesized from 12. ...

Stevens R.V., Bisacchi G.S.

Axon B.W., Davis B.R., Woodgate P.D.

Hudlicky T., Sheth J.P.

Different modes of decomposition of dienic diazoketones have been studied, leading to either formation of vinyl-cyclopropanes or Wolff-rearranged acids or esters. Preparation of four homologous dienic acids is described.

Matsumoto T., Usui S., Morimoto T.

The condensation of β-cyclocitral (4); with 3-isopropyl-4-methoxybenzyl chloride (5) in the presence of lithium naphthalenide gave an alcohol (6), which was then oxidized to the corresponding α,β-unsaturated ketone (7). The Intramolecular cyclization of 7 with polyphosphoric acid yielded (±)-12-methoxyabieta-8,11,13-trien-6-one (8) and its cis-isomer (9), which was then successfully converted into 8 via an enol acetate (11). The 8 ketone was dem ethylated with boron tribromide to give a phenol (18), and this was then reduced with lithium aluminium hydride to yield the corresponding alcohol (19). The oxidation of the C-11 position in 19 with benzoyl peroxide gave (±)-12-benzoyloxyabieta-8,11,13-trien-6β,11-diol (20), which, on reduction with lithium aluminium hydride and subsequent oxidation with Jones reagent, afforded (±)-taxodione (1). The reductive cleavage of the hydroxyl group in 6 with dichloroaluminium hydride, followed by cyclization, gave (±)-ferruginyl methyl ether (12), which was then demethyla...

de Paiva Campello J., Fonseca S.F., Chang C., Wenkert E.

Sitosterol and the following terpenic compounds have been isolated from the bark of Podocarpus lambertius: 3β-hydroxytotarol, 4β-carboxynortotarol, and macrophyllic and lambertic acids. The leaves yielded sitosterol, stigmastan-3β,5α-diol-6-one, isopimaric acid, phyllocladene, isophyllocladene, 8,9-abieten-15-ol and 17-isophyllocladenol.

Huffman J.W.

Mori K., Matsui M.

Podocarpic arid was converted to taxodione. Since the total synthesis of the former is recorded, this conversion implies a total synthesis of the latter.

Gough L.J.

Carman R., Deeth H.

Lefevre A., Guillot R., Kouklovsky C., Vincent G.

Li C., Lu F., Cai Y., Zhang C., Shao Y., Zhang Y., Liu X., Qin Y.

Yan L., Wang H., Xiong F., Tao Y., Wu Y., Chen F.

The first chloramphenicol base-derived thiourea-catalyzed enantioselective Michael addition of malononitrile to α , β -unsaturated ketones is reported. The Michael adducts were obtained in good to excellent yields (up to 98% yield) and enantioselectivities (up to 94% ee ). This reaction has a broad substrate scope to various α , β -unsaturated ketones. With this in mind, this methodology was successfully applied to the synthesis of a chiral piperidone, an advanced building block for dihydropyridinone P2X 7 receptor antagonists.

Paul Krapcho A., Ciganek E.

Abstract The Krapcho reaction involves esters with α‐electron‐withdrawing substituents such as malonates, β‐keto esters, and α‐cyano esters, which undergo dealkoxycarbonylation on being heated in polar aprotic solvents (such as DMSO, DMF, or HMPT) in the presence of water, or in polar aprotic solvents with water in the presence of added salts (such as NaCN, NaCl, LiCl, LiI, or MgCl 2 ). This procedure avoids the use of strongly aqueous acidic and alkaline conditions and tolerates many functional and protecting groups. The chapter presents the mechanistic aspects of this procedure, which include reaction parameters such as solvents, salts, other additives, and the use of microwave irradiation. The diastereoselectivity of protonation of the enolate intermediate leading to the dealkoxycarbonylated products is discussed. Trapping of the intermediate enolate by electrophiles other than a proton is illustrated. Potential side reactions and same‐pot subsequent reactions of substrates are discussed along with functional‐group compatibility for halogens and nitrogen, oxygen, sulfur, selenium, and carbon functional groups. Several examples of applications of this methodology for the synthesis of natural products along with experimental conditions and procedures are presented. Closely related methods are discussed in the Comparison with Other Methods section. The tables, which consist of 371 pages, are grouped according to substrate structure. Selective entries for other methods (excluding classical aqueous acidic or basic methods) are included in the tabular survey for comparative purposes.

Node M., Katoh T., Awasaguchi K., Mori D., Kimura H., Kajimoto T.

Optically active 2,6-dimethylcyclohexanone-2-carboxylate was prepared by PLE-catalyzed dealkoxycarbonylation of σ-symmetrical β-ketodiesters, which possess quartemary carbons at α- and α'-positions. Moreover, (-)-podocarpic acid was prepared in a short sequence from 2,6-dimethylcyclohexanone-2-carboxylate.