Semisynthesis and bioactivities of lichen substances
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Date
2007
Authors
Thadhani, Vinitha Moolchand
Journal Title
Journal ISSN
Volume Title
Publisher
University of Peradeniya
Abstract
Lichens constitute a class of small perennial plants, which are a combination of two organisms a fungal partner (mycobiont) and one or more photosynthetic partners (photobiont) growing together in symbiotic association.
In an attempt to isolate compounds from natural sources, three lichens, namely Parmotrema grayana, Cladonia sp. and Heterodermia obscurata were chemically investigated. Isolated compounds were subjected to various bioassays.
Chemical investigation of these lichens ted to the isolation of atranorin (1), + usnic acid (2), divericatic acid (3), methyl haematommate (4), methy] orsellinate (5), orcinol (6), orsellinic acid (7), lecanoric acid (8), zeorin (9), methyl-β-orcinolcarboxylate (10), lobaric acid (11), and sekikaic acid (12).
The depsides divericatic acid (3), lecanoric acid (8), sekikaic acid (12), and the depsidone lobaric acid (11) showed very significant antioxidant activity in SOIT, the IC₅₀ values being lower than the standards (propyl gallate). Simple aromatic compounds namely orciniol (6) and orsellenic acid (7), showed high urease inhibition, even higher than the standard thiourea. Methyl- 6-orcinolcarboxylate (10), methyl orsellinate (5), and the triterpenoid zeorin (9), showed significant inhibition against a-glucosidase, with IC₅₀ values several folds less than the respective standard.
The second part of thesis deals with the conversion of major lichen metabolites into minor ones and testing their bioactivities
The depiside, erythrin (13) isolated in 7.6% yield from Roccella montagnei was successfully converted into its isomeric diphenyl ether 15 via a Smiles rearrangement. Oxidative coupling of these diphenyl! ether using palladium (II) acetate, lead to an efficient and unambiguous approach to substituted dibenzofurans. To the best of our knowledge this is the first report on the formation of diphenyl ethers and dibenzofurans using naturally occurring depsides, via Smiles rearrangement.
The oxidative coupling of fully protected diphenyl ether 17 led to dibenzofuran 18 and 19. Dibenzofuran 19, earlier synthesized by completely synthetic route, has been converted to pannaric acid (24) and schizopeltic acid (25) derivatives by previous workers. Thus, our synthesis of the dibenzofuran 19 constitutes a formal synthesis of the above natural products, in a resourceful manner.
Although fully protected diphenyl ethers such as compound 17 had been used previously in the preparation of dibenzofurans, unprotected diphenyl ethers had not been subjected to oxidative coupling in the presence of palladium acetate. Oxidative coupling of free carboxylic acid containing diphenyl ethers 15 and 16 led to the dibenzofurans 21 and 20, respectively.
The dibenzofuran 20 and 21 are structural analogue of naturally occurring dibenzofuran hypostrepsilic acid (27). Thus this study opens way to form these new analogues in a versatile manner using oxidative coupling of carboxylic acid containing dipheny] ethers such as 15 and 16.
Even though the bioactivities of hypostrepsilic acid (27) and its related class of dibenzofurans are not known, very interestingly, their structural analogues 20 and 21, showed very promising activities. Both dibenzofurans showed very good activity in DPPH radical scavenging assay, and dibenzofuran 21 also was active in SOI radical scavenging assay. Dibenzofuran 20 showed antibacterial activity against Pseudomonas aeruginosa, whereas dibenzofuran 21 showed very high β- glucuronidase enzyme inhibitory activity at level higher than the standard.
The final part of thesis deals with the structure-reactivity relationship of lichen compounds (both natural and synthetic) in various bioassays. Comparison studies revealed that depsides, and depsidones showed good.antioxidant activity in SOI due to the extended conjugation of such compounds. Thus lichens have natural mechanisms or components to combat oxidative stress, which is probably why they we have shawn very promising antioxidant activities in SOI assay. On the other hand, the synthetic dibenzofurans showed good activity in DPPH assays.
Interestingly, all the simple aromatic compounds, namely orsellinic acid (7), orcinol (6), methyl-β-orcinolcarboxylate (10), methyl haematommate (4), and methyl orsellinate (5) showed very good inhibition against the enzyme urease.
Comparison studies also revealed that by simple conversion such as hydrolysis of the depside brings about drastic change to the respective bioactivity. For example, erythrin (13) was inactive against all the fungi tested whereas methyl orsellinate (5), showed significant antifungal activity against all the tested fungi.
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Keywords
Chemistry , Lichen