Podocarpic Acid Derivatives Research Articles

Phenolic diterpenoid derivatives as anti-influenza a virus agents.

A series of diterpenoid derivatives based on podocarpic acid were synthesized and evaluated as anti-influenza A virus agents. Several of the novel podocarpic acid derivatives exhibited nanomolar activities against an H1N1 influenza A virus (A/Puerto Rico/8/34) that was resistant to two anti-influenza drugs, oseltamivir and amantadine. This class of compounds inhibits the influenza virus by targeting the viral hemagglutinin-mediated membrane fusion. These results indicated that podocarpic acid derivatives may serve as potential drug candidates to fight drug-resistant influenza A virus infections.

ChemInform Abstract: Copper(I)‐Catalyzed Cycloaddition of Methyl O‐Propargylpodocarpate and Azides at Room Temperature.

AbstractAn efficient methodology for the synthesis of novel 1,2,3‐triazole derivatives of podocarpic acid via “click” chemistry cycloaddition reactions of methyl‐O‐propargylpodocarpate and propargyl‐O‐propargylpodocarpate with azides is developed.

Copper(I)-Catalyzed Cycloaddition of Methyl O-Propargylpodocarpate and Azides at Room Temperature

Copper iodide was employed as an efficient catalyst for the synthesis of 1,2,3-triazole derivatives of podocarpic acid at room temperature through “click” chemistry cycloaddition reactions of methyl O-propargylpodocarpate and propargyl O-propargylpodocarpate with azides.

ChemInform Abstract: Synthesis of Benzannulated Derivatives of Podocarpic Acid.

ChemInform Abstract: Synthesis of Benzannulated Derivatives of Podocarpic Acid.

Copper-Catalyzed Cross-Coupling Reactions of Methyl 13-Iodo-O-methylpodocarpate and Amides

Copper iodide was utilized as a relatively inexpensive catalyst (versus palladium) for the high-yield synthesis of amide derivatives of podocarpic acid. The reaction involved the one-step cross-coupling reaction of methyl 13-iodo-O-methylpodocarpate with amides.

Novel cytokine release inhibitors. Part IV: Analogs of podocarpic acid

Podocarpic acid derivatives as cytokine (IL-1β) release inhibitors are discussed.

Modifications of Rings B and C of Podocarpic Acid: Towards the Synthesis of Quassinoids Richard

Attempts to alkylate products from Birch reductions of derivatives of podocarpic acid are reported. Attempted reductive silylation of ring C of methyl 12-methoxypodocarpa-8,11,13-trien-19-oate (5) gives products of C4 ester reduction only. The enantiopure form of the bis(ethylene acetal) (15) of 19-norpodocarp-8-ene-3,12-dione, a potentially useful intermediate for quassinoid synthesis, has been prepared from the ketone (34). Functionality at C8 on the β-face has been successfully introduced by abnormal Reimer–Tiemann reactions of podocarpic acid (2) and its 13-methyl derivative (10). The saturated ketone (48) has been converted into an α,β-unsaturated ketone (18) which has potential for introducing functionality at C14.

ChemInform Abstract: Oxidative Decarboxylation of Podocarpic Acid Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Oxidative Decarboxylation of Podocarpic Acid Derivatives

The radical decarboxylation–sulfoxide cycloelimination of 2′-pyridylthio esters formed from a series of podocarpic acid derivatives gives Δ4(18) -alkenes in high yield. An exception is the 13-nitro acid (2) which affords a thiohydroxamic ester (28), the relative stability of which is attributed to inhibition of the radical chain reaction by the nitro group. The stereochemistry of the pyridyl sulfide (18) has been confirmed by X-ray crystallography.

Stereoselective synthesis and some reactions of β-( η6-arene)Cr(CO) 3 complexes of podocarpic acid derivatives

The stereoselective synthesis of a number of ( η 6-arene)tricarbonylchromium(0) complexes derived from podocarpic acid has been achieved in good to excellent yield. The stereochemistry of complexes 36 and 37 was established by X-ray crystallography. Reactions of some of the deprotonated complexes with electrophiles were investigated.

Dimers of Podocarpic Acid Derivatives

Treatment of methyl 12-hydroxypodocarpa-8,11,13-trien-19-oate (5) with a commercial sample of thallium(III) trifluoroacetate gave a low yield (5%) of a non-symmetric ether-linked dimer (15). Use of freshly prepared thallium(III) trifluoroacetate gave a 28% yield of the symmetrical biaryl dimer (16). The dimethyl ether (17) was prepared in low yield (10%) by treatment of methyl 12-methoxypodocarpa-8,11,13-trien-19-oate (4) with the latter reagent.

ChemInform Abstract: Annulations of Podocarpic Acid Derivatives via an Aryne Intermediate.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Addition-protonation reactions of ( η6-arene) tricarbonylchromium(O) complexes of podocarpic acid derivatives: synthesis of steroidal alicyclic skeletons

Functionalization of the ( η 6-arene)tricarbonylchromium(O) complexes of some podocarpic acid ( 1) derivatives has been achieved through the addition-protonation route. The resulting dienol ethers underwent acid-promoted hydrolysis giving enones which were subsequently reduced to saturated ketones. Acid-promoted cyclopentaannulation of these ketones produced compounds with tetracyclic steroidal skeletons in good yield.

ChemInform Abstract: Synthesis of Phthalide Derivatives of Podocarpic Acid via Directed ortho Metallation: A Route to Highly Substituted Octahydrochrysene Derivatives

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Benzannulation of podocarpic acid derivatives via directed ortho metallation and lithium-copper( I) transmetallation

Three podocarpic acid ( 1) derivatives have been converted into benzannulated derivatives via directed ortho metallation followed by lithium-copper( I) transmetallation, alkylation and cyclization.

Cyclopentaannulation of podocarpic acid derivatives via (η 6-arene)tricarbonylchromium(O) complexes; ring D modification

Functionalization of the (η 6-arene)tricarbonylchromium(O) complexes of some podocarpic acid ( 1) derivatives has been achieved via addition-oxidation methodology. The resulting decomplexed products underwent Lewis acid-mediated cyclopentaannulation to give ring-C aromatic androstane analogues in high yield. The D rings of these steroidal analogues were modified by both oxidation and reduction sequences, becoming structurally similar to some of the C15- or C17-oxygenated naturally occurring steroids.

Ring A modification of podocarpic acid derivatives: Functionalization and cyclopentaannulation of ring C via (η 6-arene)tricarbonylchromium(0) complexes

Modification of ring A via radical decarboxylation of the 19-carboxylic acid 2 to give the 4(18)- exo-methylene diterpenoid 6, followed by functionalization of ring C via addition-oxidation of the (η 6-arene)tricarbonylchromium(0) complex 13, has been achieved. Further oxidative modifications of ring A followed by titanium(IV) chloride-mediated cyclopentaannulation of ring C produced the ring-C aromatic androstane analogues 17 and 21, in which the A rings are structurally similar to those in some of the naturally occurring fully alicyclic steroids.

Annulations of Podocarpic Acid Derivatives via an Aryne Intermediate

The cycloaddition of substituted furans to the diterpenoid aryne (39), generated by in situ diazotization of the anthranilic acid (1) followed by cleavage of the annulated 1,4- epoxydecahydrochrysenes, provides a convenient method for the preparation in high yield of the previously unknown 1-substituted octahydrochrysen-4-ols. Use of 1,3-dipoles under the same procedure, or under a modified procedure involving pre-isolation of the diazonium tetrafluoroborate salt (9), gave novel annulated heterocyclic products directly. Attempted [2+2] cycloadditions of electron-rich alkenes to the diterpenoid aryne (39) were largely unsuccessful but reaction with 1,1-dimethoxyethene by using in situ diazotization gave a product derived from an initial [2+2] cycloaddition.

Aryne Chemistry of Podocarpic Acid Derivatives

The anthranilic acid (2), a key intermediate for the generation of an aryne at C13 of podocarpic acid derivatives, was synthesized from the 14-amino compound (5) which in turn was generated regiospecifically in high yield by treatment of the 13-bromo compound (25) with sodamide in liquid ammonia. The amine was converted into the anthranilic acid by two separate routes: firstly by directed lithiation and trapping of the lithium species with a CO2 moiety, and secondly by oxidative cleavage of an isatin fused across positions 13 and 14.

Organomanganese complexes of podocarpic acid derivatives

Cyclomanganation reactions of podocarpic acid derivatives containing aldehyde, ketone, ester, or oxime groups as directing functionalities have been investigated. Attempted complexation of amide-containing ligands proved generally to be unsuccessful whereas benzylic ketones gave their corresponding tetracarbonyl complexes in high yields. Complexation of ligands containing either two potential sites for manganation or two potential ligating groups were also investigated and the structures of the isolated complexes established unequivocally by NMR or X-ray crystallogr