Synthesis and biological properties of 2-pyranone derived molecular scaffolds
IR@CDRI: CSIR-Central Drug Research Institute, Lucknow
View Archive Info| Field | Value | |
| Creator |
Kumar, Amit
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| Date |
2014-05-12T10:29:44Z
2014-05-12T10:29:44Z 2010 |
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| Identifier |
http://hdl.handle.net/123456789/1231
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| Description |
Osteoporosis, presently standing as a major public health problem, is characterized
by low bone mass and microarchitectural deterioration of bone tissue resulting in the bone
fragility and a consequent increment in fracture risks, predominantly in the elderly
population especially in women after menopause. The incidence of fractures continues to
increase remarkably as the aged population is growing worldwide. In spite of the confirmed
curative evidence of the therapeutical approach, severe side effects of the repeated hormone
replacement therapy (HRT) have already emerged including the increased risk in the
secondary incidence of endometrial cancer, breast tumor, and venous thrombosis.
Accordingly, the current major emphasis in this regard has been focussed on searching for
novel lead compounds, which can selectively regulate bone metabolism with negligible
estrogenic action on uterus even after long-term administrations. Isoflavonoids, a subclass of
flavonoids which have structures similar to that of estrogen, have received considerable
attention as alternatives to HRT for the prevention of postmenopausal osteoporosis and their
actions suggested to be the inhibition of osteoclast differentiation.
Pterocarpans, apart from the isoflavones, represent the second largest group of
natural isoflavanoids, with medicarpin and maackiain occurring almost ubiquitously. They
are potent phytoalexins describing a defensive substance produced by plants in response to
biotic and abiotic elicitors, which are used for their antitoxin, antifungal, antiviral,
antibacterial, anti-snake venom and osteogenic activities. In this regard, based on important
literature reports, we demonstrated that pterocarpans have differential actions in osteoblasts
and parameters of acquisition of PBM in growing female rats. Given their osteogenic activity
and lack of estrogen-like effect, pterocarpans could be better prophylactic options over
existing candidates and also hold therapeutic promise in menopausal osteoporosis.
Our interest in the development of potential osteogenic agent prompted us to design
and synthesis of suitably functionalized pterocarpans, isoflavones and related compounds.
Essentially, in this thesis an attempt is made to develop highly convenient synthetic route for
chemically challenging and biologically interesting arenes and heteroarenes through ring transformation of 2H-pyran-2-ones in flexible or rigid conformations. The work incorporated in this thesis is divided into five chapters.The first chapter describes an overview on chemistry of natural pterocarpans which
mainly deals with the characteristic, conformations, classification, synthesis and reactions of
pterocarpans.
The second chapter describes synthesis and osteogenic activity of medicarpin and
cajanin. Successful synthesis and elucidation of anabolic actions of cajanin and medicarpin,
analogs of these natural products has been prepared in the exploration to their osteogenic
activities.
The third chapter describes synthesis of oxygen heterocycles such as
dihydropyranone, dihydroisocoumarine, 4-methylsulfanyl/sec-amino-2-oxo-2,5,6,7-
tetrahydro-1-oxa-dibenzo[a,c]cycloheptene-3-carbonitrile and pyran, and
dibenzo[a,c]cycloheptene. These compounds have been synthesized from α-pyranones
through carbanion induced ring transformation strategy.
The fourth chapter describes synthesis of biaryls and arylated benzene scaffolds.
We have prepared functional group demanding unsymmetrical biaryls, appended with
methoxy group near biaryl axis, and α-methylstyrenes through carbanion-induced ring
transformation of functionalized 6-aryl- α-pyrones in excellent yields. This chapter also
deals with cyclotrimerization of various methyl ketone in the presence of Amberlyst 15.
The chapter five of thesis describes the synthesis and interesting photophysical
properties of phenylethynyl arenes and dibenzofurans prepared through novel ring
transformation approach.
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| Format |
7413347 bytes
application/pdf |
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| Language |
en
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| Relation |
CSIR-CDRI Thesis No. - K-112
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| Subject |
2-Pyranone
scaffolds |
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| Title |
Synthesis and biological properties of 2-pyranone derived molecular scaffolds
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| Type |
Thesis
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