Podocarpic acid synthesis

An alternative synthesis of the tricyclic intermediate (168), together with the elaboration of C-4 with the configuration of both podocarpic and dehydroabietic acids, has been reported. In a stereoselective total synthesis of ( )-callitrisic acid and ( )-podocarpic acid, the C-4 stereochemistry was established by reductive methylation of the enol-ether (169). 

In 1971, Zalkow and co-workers reported (175) the conversion of podocarpic acid (322) to a key intermediate 323 for the synthesis of the enatiomers of ajaconine (80) and atidine (79). Compound 323 contains the... 

Pinhey utilized the decarboxylative rearrangement of 2 to the nor-alkyl pyridyl sulfide 3, oxidation to the corresponding sulfoxide and thermal elimination sequence in a simple transformation of podocarpic acid 4 into useful synthons 5 (for example, in vitamin D3 synthesis) for steroid CD-ring systems, as shown in Scheme l.8... 

The use of acylnitiene cyclizations in the synthesis of diteipene alkaloids goes back to the early 1960s, and although much of the early work has been reviewed, selected examples are included here. The acyl azide (19), readily prepared from podocarpic acid, was irradiated to give the 8-lactam (20 20%), which has the azabicyclononane ring system of the diteipene alkaloids such as atisine. ... 

Isomerization of the diterpeue A B ring juncture. The steroidal type A/B ring juncture of diterpenes can be isomerized to the antipodal one by treatment with a 10% palladium-charcoal catalyst in refluxing triglyme. Thus methyl 5a,10 -podocarpa-8,1 l,13-triene-15-oale (1) can be isomerized in 83% yield to methyl 5j, IOa-podocarpa-8,ll,13-triene-l3-oate (2). The reaction was used in a synthesis of (- J-podocarpic acid from (+)-dehydroabietic acid. 

The Chemistry of Ring A.—Two methods have been described for smoothly hydrolysing the highly-hindered axial C-4 methyl esters such as methyl 0-methyl podocarpate. The first uses boron trichloride in methylene chloride, and the otherlithium n-propyl mercaptide in hexamethylphosphoramide. The oxidative decarboxylation of dehydroabietic acid and 0-methyl podocarpic acid affords a mixture of C-4 olefins which are separable over 10 % silver nitrate by t.l.c. Thus in a partial synthesis of callitrisic acid, the 4(19)-epoxide prepared... 

Studies aimed at the synthesis of the tetracyclic steroid skeleton from dehydro-abietic acid have centred, in their initial stages, on transformations of the C-13 isopropyl group. The full paper describing the conversion of methyl 12-acetyl-abieta-8,ll,13-trien-18-oate into methyl 13-hydroxypodocarpa-8,ll,13-trien-18-oate by nitrodeacylation and dealkylation reactions, has appeared. Birch reduction of the methyl ether of the phenol afforded the a/5-unsaturated ketone (56) which is a useful synthetic intermediate. Methods for the conversion of podocarpic acid into the a) -unsaturated ketones (57 R = CO2H and CHjOAc) have been investigated reduction of the ester (58 R = C02Me) with lithium in liquid ammonia, which was accompanied by decarboxylation, gave only a... 

The tricyclic alcohol (130) is an intermediate in the synthesis of rimuene. Hydroboronation of its tetrahydropyranyl ether and then oxidation with iodine and lead tetra-acetate afforded the 6—18 ether which could be cleaved and oxidized to a keto-acid. Such derivatives might form suitable intermediates for the synthesis of the rosane lactones. O-MethyI-14-methyl podocarpic acid has been synthesized "" by a conventional ring a + ring c route. 

A number of partial syntheses have been described in the bicyclic series. The synthesis of methyl (12S)- and (12i )-hydroxylabda-8(17)-en-19-oate utilized the aldehyde (10) as an intermediate. This was obtained from podocarpic acid. The synthesis of the furan methyl lambertianate (11) from dimethyl agathate has been described. Examination of the n.m.r. spectra of the levantenolides (12) has led to a revision of their C-12 stereochemistry. a-Levantenolide has the (12i ) configuration whereas jS-levantenolide has the (125) configuration. The functionalization at C-12 of labdanes by oxidation of C-15 alcohols with iodine and lead tetra-acetate has been described. ... 

Bicycloannelation.2 The a -enolate of an a,/J-cyclohexenone reacts with this phosphonium salt to form a tricyclo[3.2.1.02 7]octane in low to moderate yield. This reaction was used in a short synthesis of the pentacyclic diterpene trachyloban-19-oic acid (4). Reaction of the lithium enolate of 2, prepared from podocarpic acid, with I provided the pentacyclic ketone 3, which was reduced by the Wolff-Kishner reaction to 4. 

It was most convenient to isolate the products after acidic conversion to cyclohexenones. Structures of the products were assigned by chemical correlation and circular dichroism and the enantiomeric purities were based on optical rotations. The selectivities obtained, although impressive for the era, are moderate at best, despite significant attempts to optimize the substrates and reaction conditions. Use of substituted cyclohexanones (29) and other aldehydes (30) lead to optically active products but the extent of enantiomeric induction in these products was not determined. This technology was used for the partial asymmetric synthesis of (+ )-mesembrine (12.1) (29) and (+ )-podocarpic acid (12.2) (31). 

C, Synthesis.—Atisine and Veatchine Types. Zalkow and co-workers developed syntheses of intermediates potentially transformable into atisine-type alkaloids, starting with podocarpic acid. The general approach is illustrated by a synthesis" of an ajaconine degradation product. Methyl O-methyl-7-keto-podocarpate (56) was reduced to the diol, which was converted by Birch reduction to dienone (57). The diene diol diacetate from this was converted to the 7,8-epoxide. Boron trifluoride converted this to the non-conjugated enone (58) which isomerised and... 

Synthesis and carbon-13 NMR study of some podocarpic acid derivatives Ortellado, Maria Amelia A. C. Marsaioli, Anita J. 

Syntheses Directed toward Ajaconine and Atidine. The conversion of podocarpic acid (92) into a key intermediate (93) in the synthesis of the enantiomers of the diterpene alkaloids ajaconine (94) and atidine (50) has been reported by 2 1kow and co-workers. The pentacyclic unsaturated keto-lactam (93) was prepared... 

A synthesis of methyl vinhaticoate and methyl vouacapenate has been described. The key steps involved the conjugate addition of dimethylcopper lithium to (128), prepared from podocarpic acid, the transformation of the product (129) into the methoxymethylene ketone (130), and the formation of the furan ring (131) by the copper-catalysed addition of ethoxycarbonylcarbene. 

Synthesis and Fungistatic Activity of Podocarpic Acid Derivatives... 

Commercial podocarpic acid is derived from naturai sources. Several recent studies have been directed towards the total synthesis of this resin acid to assure adequate future supplies of this material for use in agriculture and medicine (24,25). 

The synthesis of methyl D-podocarpate (3) is typical of the transformations that can be carried out with Mn(OAc)3. Oxidation of 1 with 2 equivalents of Mn(OAc)3 in AcOH at 15 °C afforded 50% of 2 as a single isomer that has been converted to methyl 0-methylpodocarpate by Clemmensen reduction (26). Both enantiomers of O-methylpodocarpic acid have been prepared using the appropriate phenylmenthyl ester (49). 

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