Abstract:
The work presented in this thesis consists of the synthesis, characterization, and
biological screening of heterocyclic compounds. For convenience, the work has
been divided into two parts, part one is related to the compounds containing
oxygen atom in the heterocyclic ring whereas part two refers to the compounds
containing nitrogen and/ or sulphur atoms in the heterocyclic ring.
Part one of this thesis is related to the synthesis, characterization and biological
activity of some heterocyclic compounds containing oxygen in the ring. These
compounds include some naturally and unnaturally occurring substituted
isocoumarins and 3,4-dihydroisocoumarins. The synthesis of naturally occurring
isocoumarin Thunberginol B is reported, in which 3,5-dimethoxyhomophthalic
acid
is a key intermediate for the synthesis of Thunberginol B. It was
synthesized efficiently in five steps from 3,5-dimethoxybenzaldehyde via a series
of reactions including synthesis of 3,5-dimethoxycinnamic acid, 3-(3′,5′-
dimethoxyphenyl)propionic acid, cyclization of 3-(3′,5′-dimethoxyphenyl)propionic
acid to 5,7-dimethoxy-1-indanone and oxidative decomposition of methyl 2-
hydroxy-2-(5,7-dimethyoxy-1-oxo-1H-inden-2(3H)-ylidene)acetate
dimethoxyhomophthalic acid. 3,4-Dimethoxybenzoylchloride
from 3,4-dimethoxybenzoic acid
condensation
with
to
3,5-
was prepared
on reaction with thionyl chloride which on
3,5-dimethoxyhomophthalic
acid
afforded
3-(3',4'-
dimethoxyphenyl)-6,8-dimethoxyisocoumarin. Complete demethylation of 3-(3',4'-
dimethoxyphenyl)-6,8-dimethoxyisocoumarin with hydrobromic acid in acetic acid
gave 3-(3',4'-dihydroxyphenyl)-6,8-dihydroxyisocoumarin (Thunberginol B). In
addition to above, some unnaturally occurring halogenated isocoumarins and
their 3,4-dihydrodrivatives were also synthesized. The difluorophenyl- and
dichlorophenylisocoumarins by condensation of homophthalic acid with an
appropriate acid chloride. Alkaline hydrolysis of the isocoumarins yielded
corresponding keto-acids, which on reduction give the corresponding racemichydroxy-acids. 3,4-Dihydroisocoumarins were obtained from these racemic
hydroxy-acids by cyclodehydration using acetic anhydride.
All the synthesised compounds were identified using their IR, 1 H NMR and mass
spectral data. In many cases
13
C NMR and elemental analysis data were
employed to support the characterization. In each case, a plasible mass
fragmentation pattern is suggested. The synthesized compounds were screened
for their antifungal, antibacterial, herbicidal, insecticidal, fungicidal, anti-
metastatic, brine shrimp lethality, antioxidant, anti -inflammatory, antiviral, anti-
HIV, anti-HBV and anticancer activities and in some cases, very fascinating
results were obtained which were then published in different international
journals. These synthetic schemes have tremendous potential for further
synthesis of novel biological active compounds.
Part two of the thesis describes the synthesis and biological screening of some,
hitherto
unreported,
isatin
derivatives
(Indolinones),
1,4-disubstituted
thiosemicarbazides and their related 2,5-disubstituted-1,3,4-thiadiazoles and 4,5-
disubstituted-3H-1,2,4-triazole-3-thiones. Indolinones were formed by the direct
condensation of hydrazides with halogenated isatins. Triazoles were formed by
intramolecular dehydrative cyclization of thiosemicarbazides in basic media while
thiadiazoles were formed in acidic media, which is an intermediate during the
synthesis of various heterocyclic compounds. Thiosemicarbazides were formed
by aldol type condensation reaction of acid hydrazides and isothiocyanates.
Isothiocyanates were formed by the reaction of anilines with carbon disulphide in
ammonium hydroxide solution to yield ammonium dithiocarbamate, an
intermediate which on oxidation with lead nitrate yield isothiocyanate. Acid
hydrazides were formed by the reaction of esters of carboxylic acid with
hydrazine hydrate and esters were formed by refluxing carboxylic acid in
methanol in catalytic amount of carboxylic acids. As a result of these synthetic
schemes, thirty new indolinones, ten disubstituted-1,3,4-thiadiazoles and twenty
disubstituted 1,2,4-triazole-3-thiones were synthesized. The characterization ofthese synthesized compounds was carried out by IR, 1 H NMR,
13
C NMR,
elemental analysis, Mass spectral data and XRD analysis. The synthesized
compounds were screened for their antifungal, antibacterial, herbicidal,
insecticidal, fungicidal, plant growth regulatory activity and antiviral activities.