| dc.description.abstract | Chapter 1
This chapter is devoted to the isolation and structure elucidation of some natural products which are important as drugs in the Indian system of medicine.
Section 1 (i): The chemistry of Barringtonia species is briefly reviewed, emphasizing their medicinal value and the isolation and structure determination of various neutral and acidic compounds from them.
Section 1 (ii): Here the isolation of a new pentacyclic triterpene dicarboxylic acid, named bartonic acid, from the berries of B. speciosa is presented.
The structure of bartonic acid is established as 2?,3?,19?-trihydroxyolean-12-ene-24,28-dioic acid, based on spectral data and chemical reactions. Its conversion into sericic acid, a pentacyclic triterpene of known absolute stereochemistry, confirmed the above structure. Bartonic acid is isolated from the chloroform and methanol extracts of the berries of B. speciosa and is purified as its dimethyl ester.
The pentacyclic skeleton as well as the olean-12-ene system follow from the color reactions, PMR and mass spectral data of dimethylbartonate and diacetyldimethylbartonate. PMR spectra of dimethylbartonate and its diacetate show the presence of two carboxymethyl groups. The diacetate of dimethylbartonate contains a hindered hydroxyl group as revealed from the IR and analytical data. Acetylation in presence of catalytic amount of perchloric acid results in a triacetate confirming the presence of the hindered hydroxyl function.
Mass spectral data of diacetyldimethylbartonate place one carboxymethyl group and the hindered hydroxyl group in the rings D or E. The other two easily acylable hydroxyl groups are placed in ring A and proved as a 2?,3?-glycol on the basis of PMR data, periodate oxidation and diosphenol reaction. The hindered hydroxyl group is positioned at C-19 based on Jones reagent oxidation of diacetyldimethylbartonate and the isomerisation of the so-formed ketone. The configuration of 19-OH is proved to be ?-based on the dehydration experiments using selenium dioxide and phosphorus oxychloride yielding a 11,13(18)-diene having a characteristic triple UV absorption maxima.
However, the establishment of bartonic acid as a C-24 carboxylic acid is the highlight of this structural work since only a few instances of pentacyclic triterpenes belonging to ?-amyrin group with a C-24 carboxyl group are known. Further, bartonic acid is the first C-24 oxygenated compound from Barringtonia species and thus biogenetically significant. Diacetyldimethylbartonate upon selective reduction using sodium bis-[2-methoxyethoxy] aluminium hydride (Vitride reagent) gives methylsericiate, a compound of defined structure and stereochemistry and possessing a C-24 hydroxymethyl group as evidenced from the PMR data and comparison with authentic samples.
The PMR spectra of triterpenes having a 23-CH?OAc or 24-CH?OAc differ considerably in the chemical shifts of the methylene protons of CH?OAc and their pattern. This can be of diagnostic value as exploited in the case of diacetyldimethylbartonate. Thus the protons of 23-CH?OAc exhibit non-equivalence and appear as a quartet (J = 10 Hz) at ? 3.65 whereas the protons of 24-CH?OAc resonate as a sharp singlet at ? 4.18. Thus the structure of bartonic acid is conclusively established as 2?,3?,19?-trihydroxyolean-12-ene-24,28-dioic acid. Supporting evidence is based on the deshielding of 2?-H due to the presence of the 24-carboxyl group of diacetyldimethylbartonate. Further comparison (IR, NMR, CMR and ORD) of the derivatives prepared from bartonic acid and arjunolic acid confirmed the above structure. CMR spectra of dimethylbartonate, methylsericiate, methylarjunolate and methyloleanolate are also discussed.
Section 2 (i): A brief introduction to the chemistry of Clausena species highlighting their medicinal value and structure of the compounds isolated from them is presented.
Section 2 (ii): The isolation of three furanoterpenes, ?-, ?- and diclausenan from the leaves of C. wightdenovii is described. Further evidences are presented to confirm the structure of ?-clausenan as 3-methyl-2-(3-methylbut-4-enyl)-furan. The structure of ?-clausenan is deduced as 3-methyl-2-(3-methylbuta-1,3-dienyl)-furan from the analysis of its PMR spectral data. Diclausenan is shown to be a dimer of ?-clausenan from its PMR data and chemical reactions. The structures assigned for ?-, ?- and diclausenan are further confirmed from the analysis of their CMR spectral data.
The isolation and structure elucidation of 3-(1,1-dimethylallyl)-xanthyletin, a known coumarin, from the root as well as the bark of C. wightdenovii by cold percolation with hexane is also described in this section. The structure of this coumarin is further confirmed from its CMR spectrum.
Chapter 2
In this chapter, the application of dihydroaromatic compounds, derived from metal-ammonia reductions of aromatic substrates, in synthesis is exploited.
Section 1: A brief account of the reduction of aromatic systems with metal-ammonia solutions and the use of these dihydroaromatic compounds in organic synthesis is presented.
Section 2: This is subdivided into three parts:
(i) The synthesis of a C-7 synthon, a potential fragment for the synthesis of Vitamin A, is described. Thus 1-methoxycyclohexa-1,4-diene is selectively cleaved at the enol ether double bond to afford cis-methyl-6-hydroxy-3-methylhex-3-enoate. The stereochemistry of this compound was established by comparison with the isomeric trans-compounds, prepared from cyclopropylmethylketone. Attempted coupling between C-7 fragments and ?-ionone is also described.
(ii) An efficient synthesis of substituted 3-methoxyphthalic acids, from 1-methoxycyclohexa-1,4-dienes, obtained from the metal-ammonia reduction of anisoles, with dimethyl-acetylenedicarboxylate (DAD) in presence of dichloromaleic anhydride (DCMA) as catalyst, is described. These 3-methoxyphthalic acids constitute the main nucleus of several fungal metabolites.
(iii) Experiments towards the stereospecific synthesis of spiro systems with special reference to the synthesis of chamigrenes is described. The reaction between 6-methoxy-1,2,3,4,5,8-hexahydronaphthalene and methyl acrylate gives the tricyclic adduct which is cleaved by ozonolysis to the spiro skeleton. Further attempts to introduce the double bond in a regioselective manner are also described. | |
