L-abietic Acid Research Articles

Synthesis and biological evaluation of 20-hydroxytriptonide and its analogues

20-Hydroxytriptonide was synthesized from readily accessible l-abietic acid in 22 linear steps, which features a Barton reaction carried out under air atmosphere to install the C20-hydroxy group. Meanwhile, we also synthesized (5R)-5-hydroxytriptolide's probable metabolite product. Preliminary structure–activity relationship studies revealed that C20-angular methyl group might play a key role in maintaining the electronic properties of the whole molecule, which was essential for retaining the cytotoxic activity and might easily and inevitably be affected by the introduction of a new group.

Synthesis of (+)-amberketal and its analog from l-abietic acid

(+)-Amberketal ( 1) and its analog ( 2) have been synthesized from commercially available l-abietic acid ( 3) by a selective reduction of an unsaturated aldehyde in the presence of a ketone and simultaneous reduction of an iodide using an aqueous suspension of Raney Ni as the key step.

Synthesis of (-)-ambrox from ℓ-abietic acid

Synthesis of (-)-ambrox 1 has been completed stereoselectively starting from ℓ-abietic acid 2.

Synthesis of (-)-DRIM-7-ENE-9α, 11, 12 Triol. The Direct Precursor of (-)-Warburganal

Abstract Warburganal (1)1 isolated from the African medicinal tree Warburgia ugandensis, has been shown to possess interesting biological properties2,3 including antifeedant and molluscicidal activities. For this reason and to study structure-activity relationship, this sesquiterpene has recently received intense attention and several independent syntheses4 have been reported. However, the only synthesis of chiral warbur-ganal (1) has been achieved, in fourteen steps by Okawara et al.4 using l-abietic acid as starting material.

ChemInform Abstract: DITERPENOIDS. XLII. STEREOSELECTIVE SYNTHESIS OF D‐PHYLLOCLADENE FROM L‐ABIETIC ACID

AbstractDer aus 1‐Abietinsäure herstellbare Diester (I) wird durch katalytische Hydrierung, anschließende Oxidation und Cyclisierung stereoselektiv in das Diketon (II) umgewandelt, dessen eine Ketogruppe durch Thioketalisierung und Behandlung des Monothioketals mit Raney‐Nickel entfernt wird.

Diterpenoids. XLII. Stereoselective synthesis of d-phyllocladene from l-abietic acid.

Stereoselective conversion of l-abietic acid (1) to d-phyllocladene (16) was achieved by the use of two carbon units of the isopropyl group in 1 for the formation of its D-ring. Catalytic hydrogenation of methyl 13-methoxycarbonylmethyl-7-oxopodocarpa-8, 11, 13-trien-15-oate (2), derived from 1, over ruthenium oxide, followed by oxidation, gave stereoselectively methyl 13β-methoxycarbonylmethyl-7-oxopodocarpan-15-oate (4), without loss of the 7-oxygen function. Although attempts of cyclization reaction of methyl 7-hydroxy-13β-(2'-hydroxyethyl)-podocarpan-15-oate (6) to methyl 15-hydroxy-7-oxo-17-norphyllocladan-18-oate (7) were fruitless, the formation of the D-ring from methyl 13β-carboxymethyl-7-oxopodocarpan-15-oate (5) was accomplished by polyphosphoric acid-AcOH treatment to give methyl 7, 15-dioxo-17-norphyllocladan-18-oate (9) in high yield. Selective removal of the 7-oxygen function of 9, via monothioketalization, yielded methyl 15-oxo-17-norphyllocladan-18-oate (11), which was further converted to methyl 17-norphylloclad-15-en-18-oate (14). Hydroboration of 14, followed by oxidation, gave methyl 16-oxo-17-norphyllocladan-18-oate (15) accompanied with 11.

Diterpenoids. XLIV. A-ring bromination of abietane skeleton and the synthesis of teideadiol.

Direct introduction of bromine into the A-ring of the phenacylidene derivatives of l-abietic acid (1) was developed and it was applied to the conversion of 1 into teideadiol (2), a naturally occurring diterpene with a hydroxy group on the A-ring of its abietane skeleton.

アビエチン酸の化学的性質 生理活性天然物の合成をめざして

The study of the chemical conversion of l-abietic acid (1), main component of pine rosin, into optically active natural products with biological activity has been developed at the Institute of Physical and Chemical Research by the late Dr. Akira Tahara. This group's recent works are reviewd for his memory by his staffs.Various types of the acid rearrangements in phenacylidene derivatives of (1) were disclosed and applied to the syntheses of the A-ring substituted diterpenes and a possible intermediate to grayanotoxins. Selective functionalization at 11-, 13-and 14-positions of the aromatic C-ring were established. The 11-substitution reaction was applied to the synthesis of taxodione. Ozonolysis of the phenolic C-ring was proved to be a convenient method for the cleavage of the ring and used for the short-step synthesis of drimane-type sesquiterpenes. Modifications of the isopropyl group, including its methyl migration, made it possible to synthesize d-phyllocladene, d-kaurene, and the skeletons of pimaric acid and steroids. Finally, the synthesis of gibberellin A12 was completed by the combination of the skeletal transformation and the functionality modification of (1).

Diterpenoids. XXXVI. Synthesis of d-kaurene and d-phyllocladene from l-abietic acid.

d-Kaurene (XXXVI) and d-phyllocladene (XXXVII) were synthesized from l-abietic acid (I) via intramolecular carbenoid reaction of diazoketones and subsequent cleavage of the resulting cyclopropyl ring with Li-liq. NH3. Methyl dehydroabietate (XVI) and dehydroabietane (V) introduced from I were used as the starting materials. The improved synthesis of V was also described.

Diterpenoids. XXXV. A-ring substitution of hydrofluorene compound derived from l-abietic acid.

Diterpenoids. XXXV. A-ring substitution of hydrofluorene compound derived from l-abietic acid.

Diterpenoids. XXXIV. Stereochemistry on the rearranged compound (benzilic acid rearrangement) of methyl 6,7-dioxo-5.ALPHA.,10.ALPHA.-podocarpa-8,11,13-trien-15-oate.

Stereochemistry of the hydroxy diacid (III), which was obtained by the benzilic acid rearrangement of the dioxo ester (II) derived from l-abietic acid (I), was determined uneqivocally. Moreover, the rearranged compounds (III and IX) were concluded to have a nonsteroidal form.

Diterpenoids. XXXVIII. Conversion of l-abietic acid into steroidal skeletons: Formation of the D-ring. I.

The steroidal D-rings (31 and 37), along with 32 and 38, were synthesized by the use of a part or whole of the carbon units of the isopropyl group of l-abietic acid (1), via oxidation of 18 or 20 with Tl (ONO2)3, or addition reaction of 20 with 1, 1-dichloroethylene, and modifications of the functionality, followed by Friedel-Crafts cyclization. Cyclization to the 14-position (formation of 31 or 37) in 30 or 35 was always predominant over that to the 12-position (formation of 32 or 38). In attempts for functionalization of the isopropyl group with Pb (OAc)4, 9, a hopeful intermediate to syntheseze quinoid diterpenes, was obtained via 3, 4, 5 and 6. RuO2 reduction of 6 and successive Pb (OAc)4 oxidation to 17 is also described.

Transformation of l-abietic acid to benzohydroazulene derivative.

Transformation of l-abietic acid to benzohydroazulene derivative.

Diterpenoids. XXIV. Transformation of Podocarpic Acid Type Diterpene to B-Homo-C-nor-5β, 10α-podocarpan Skeleton

A skeletal transformation of XI, drived from l-abietic acid (I), was tried by the cleavage of B/C-ring juncture and successive condensation. The ether bridge suppresses the condensation direction as in the synthesis (VII→VIIIa) previously reported, and then, the cyclization gives XVIa regarded as a mother skeleton of aconitine.

Diterpenoids. XXVII. Synthesis of 11-Methoxy-diterpenoids.(2). Synthesis of 11-Methoxy-dehydroabietic Acid Derivatives

7-Oxo-dehydroabietamide (XI) derived from l-abietic acid (III) was converted to methoxycyano acid (XVI) via cyano lactone (XIII) and the intramolecular cyclization of XVI gave the expected 11-methoxy-7-oxo-dehydroabietonitrile (XVII). The cyclized compound (XVII) was converted to some 11-methoxy-dehydroabietic acid derivatives, which could be regarded as potential intermediates for synthesis of natural products having 11-hydroxyabietane skeleton.

Diterpenoids. XXVI. Synthesis of 11-Methoxy-diterpenoids.(1). Synthesis of Antipodal 11-Methoxy-deoxypodocarpic Acid Derivatives

7-Oxo esters (IV) and (V) derived from l-abietic acid (III) were converted to half esters (XI) and (XV), respectively. Intramolecular cyclization of XV gave the expected 11-methoxy oxo ester (XVI), but that of XI yielded the undesirable bicyclo [3, 3, 1] n onane ester (XVII) via a methoxy migration of the methoxy carbonyl group. 11-Hydroxy diterpenoid is not only a potential intermediate for the syntheses of taxodione (I) and callicarpone (II), but also is regarded as an important substance for an oxidative substitution of A-ring or 10-methyl group from its 11-hydroxyl group.

Study on Synthesis of Antipodal Steroid

Conversion of l-abietic acid, the main component of pine rosin, to steroids was planned, and syntheses of the ketone compounds (VI and VII), important intermediates in the synthesis of the skeleton of steroid antipodes, was successfully concluded in the present series of work. Since the conversion of these VI and VII to steroidal skeleton is already known in analogous compounds, availability of these intermediates has opened a way for the synthesis of steroid antipodes from diterpenes.

Diterpenoids. 8. Synthesis of skeleton of dipterpene alkaloid.

From l-abietic acid, a basic skeleton compound (XX) having same absolute configuration and characterized nitrogen bridge of diterpene alkaloid, was accomplished to synthesize.

Diterpenoids. IX. Chemical conversion to diterpene alkaloid from abietic acid.

By confluence from l-abietic acid at the key intermediate (XXIV) for Nagata's total synthesis of dl-atisine (I), dl-veatchine (II) and dl-garryine (III), the first example of total synthesis of the natural diterpene alkaloid from the other natural diterpene, was accomplished.

On the Conversion of l-Abietic Acid into a d-Abietic Acid

On the Conversion of <i>l</i>-Abietic Acid into a <i>d</i>-Abietic Acid