The Experts below are selected from a list of 105 Experts worldwide ranked by ideXlab platform
J. Šajbidor - One of the best experts on this subject based on the ideXlab platform.
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Biotechnological production of Prostaglandins
Applied Microbiology and Biotechnology, 1997Co-Authors: M. Lamačka, J. ŠajbidorAbstract:The metabolism of 20-carbon polyunsaturated fatty acids, particularly arachidonic acid, by prostaglandin H synthase results in a wide range of oxidized products with potent biological activities. Among these metabolites, a group of compounds called Prostaglandins has drawn the attention of both scientists and medical practitioners. Prostaglandins can be manufactured from polyunsaturated fatty acids with the help of enzymes from mammals. The yield of the desired prostaglandin can be increased by means of various activators, enzyme recycling, immobilised enzymes or semibatch processes with either continuous or stepwise addition of the substrate. [References: 46]
Varinder K Aggarwal - One of the best experts on this subject based on the ideXlab platform.
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stereocontrolled organocatalytic synthesis of prostaglandin pgf2 agr in seven steps
Nature, 2012Co-Authors: Graeme Coulthard, Varinder K AggarwalAbstract:A concise new synthesis of the most complex of the Prostaglandins—diverse hormone-like chemical messengers—should make existing prostaglandin-based drugs cheaper and also facilitate other related syntheses. Prostaglandins are hormone-like chemical messengers that regulate a broad range of physiological activities, including blood circulation, digestion and reproduction. Their biological activities and their complex molecular architectures have made Prostaglandins popular targets for synthetic organic chemists for more 40 years. In this manuscript, the authors report a concise synthesis of the most complex prostaglandin, PGF2α. Access to this compound should not only render existing prostaglandin-based drugs more affordable, but will also facilitate the rapid exploration of chemical space around the ubiquitous five-membered ring motif. Prostaglandins are hormone-like chemical messengers that regulate a broad range of physiological activities, including blood circulation, digestion and reproduction1,2. Their biological activities and their complex molecular architectures have made Prostaglandins popular targets for synthetic organic chemists for over 40 years3,4. Prostaglandin analogues are widely used as pharmaceuticals and some, such as latanoprost, which is used to treat glaucoma5,6, have become billion-dollar drugs. Previously reported syntheses of these compounds are quite lengthy, and every chemical step costs time and energy, generates waste and is accompanied by material losses. Using a new bond disconnection, here we report a concise synthesis of the most complex prostaglandin, PGF2α, with high levels of control of relative and absolute stereochemistry, and fewer steps. The key step is an aldol cascade reaction of succinaldehyde using proline organocatalysis to create a bicyclic enal in one step and an enantiomeric excess of 98%. This intermediate bicyclic enal is fully primed with the appropriate functionality for attachment of the remaining groups7. Access to this bicyclic enal will not only render existing prostaglandin-based drugs more affordable, but will also facilitate the rapid exploration of related chemical structures around the ubiquitous five-membered ring motif, such as potentially therapeutic prostaglandin analogues.
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Stereocontrolled organocatalytic synthesis of prostaglandin PGF_2α in seven steps
Nature, 2012Co-Authors: Graeme Coulthard, Varinder K AggarwalAbstract:Prostaglandins are hormone-like chemical messengers that regulate a broad range of physiological activities, including blood circulation, digestion and reproduction. Their biological activities and their complex molecular architectures have made Prostaglandins popular targets for synthetic organic chemists for more 40 years. In this manuscript, the authors report a concise synthesis of the most complex prostaglandin, PGF_2α. Access to this compound should not only render existing prostaglandin-based drugs more affordable, but will also facilitate the rapid exploration of chemical space around the ubiquitous five-membered ring motif. A concise new synthesis of the most complex of the Prostaglandins—diverse hormone-like chemical messengers—should make existing prostaglandin-based drugs cheaper and also facilitate other related syntheses. Prostaglandins are hormone-like chemical messengers that regulate a broad range of physiological activities, including blood circulation, digestion and reproduction^ 1 , 2 . Their biological activities and their complex molecular architectures have made Prostaglandins popular targets for synthetic organic chemists for over 40 years^ 3 , 4 . Prostaglandin analogues are widely used as pharmaceuticals and some, such as latanoprost, which is used to treat glaucoma^ 5 , 6 , have become billion-dollar drugs. Previously reported syntheses of these compounds are quite lengthy, and every chemical step costs time and energy, generates waste and is accompanied by material losses. Using a new bond disconnection, here we report a concise synthesis of the most complex prostaglandin, PGF_2α, with high levels of control of relative and absolute stereochemistry, and fewer steps. The key step is an aldol cascade reaction of succinaldehyde using proline organocatalysis to create a bicyclic enal in one step and an enantiomeric excess of 98%. This intermediate bicyclic enal is fully primed with the appropriate functionality for attachment of the remaining groups^ 7 . Access to this bicyclic enal will not only render existing prostaglandin-based drugs more affordable, but will also facilitate the rapid exploration of related chemical structures around the ubiquitous five-membered ring motif, such as potentially therapeutic prostaglandin analogues.
M. Lamačka - One of the best experts on this subject based on the ideXlab platform.
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Biotechnological production of Prostaglandins
Applied Microbiology and Biotechnology, 1997Co-Authors: M. Lamačka, J. ŠajbidorAbstract:The metabolism of 20-carbon polyunsaturated fatty acids, particularly arachidonic acid, by prostaglandin H synthase results in a wide range of oxidized products with potent biological activities. Among these metabolites, a group of compounds called Prostaglandins has drawn the attention of both scientists and medical practitioners. Prostaglandins can be manufactured from polyunsaturated fatty acids with the help of enzymes from mammals. The yield of the desired prostaglandin can be increased by means of various activators, enzyme recycling, immobilised enzymes or semibatch processes with either continuous or stepwise addition of the substrate. [References: 46]
Graeme Coulthard - One of the best experts on this subject based on the ideXlab platform.
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stereocontrolled organocatalytic synthesis of prostaglandin pgf2 agr in seven steps
Nature, 2012Co-Authors: Graeme Coulthard, Varinder K AggarwalAbstract:A concise new synthesis of the most complex of the Prostaglandins—diverse hormone-like chemical messengers—should make existing prostaglandin-based drugs cheaper and also facilitate other related syntheses. Prostaglandins are hormone-like chemical messengers that regulate a broad range of physiological activities, including blood circulation, digestion and reproduction. Their biological activities and their complex molecular architectures have made Prostaglandins popular targets for synthetic organic chemists for more 40 years. In this manuscript, the authors report a concise synthesis of the most complex prostaglandin, PGF2α. Access to this compound should not only render existing prostaglandin-based drugs more affordable, but will also facilitate the rapid exploration of chemical space around the ubiquitous five-membered ring motif. Prostaglandins are hormone-like chemical messengers that regulate a broad range of physiological activities, including blood circulation, digestion and reproduction1,2. Their biological activities and their complex molecular architectures have made Prostaglandins popular targets for synthetic organic chemists for over 40 years3,4. Prostaglandin analogues are widely used as pharmaceuticals and some, such as latanoprost, which is used to treat glaucoma5,6, have become billion-dollar drugs. Previously reported syntheses of these compounds are quite lengthy, and every chemical step costs time and energy, generates waste and is accompanied by material losses. Using a new bond disconnection, here we report a concise synthesis of the most complex prostaglandin, PGF2α, with high levels of control of relative and absolute stereochemistry, and fewer steps. The key step is an aldol cascade reaction of succinaldehyde using proline organocatalysis to create a bicyclic enal in one step and an enantiomeric excess of 98%. This intermediate bicyclic enal is fully primed with the appropriate functionality for attachment of the remaining groups7. Access to this bicyclic enal will not only render existing prostaglandin-based drugs more affordable, but will also facilitate the rapid exploration of related chemical structures around the ubiquitous five-membered ring motif, such as potentially therapeutic prostaglandin analogues.
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Stereocontrolled organocatalytic synthesis of prostaglandin PGF_2α in seven steps
Nature, 2012Co-Authors: Graeme Coulthard, Varinder K AggarwalAbstract:Prostaglandins are hormone-like chemical messengers that regulate a broad range of physiological activities, including blood circulation, digestion and reproduction. Their biological activities and their complex molecular architectures have made Prostaglandins popular targets for synthetic organic chemists for more 40 years. In this manuscript, the authors report a concise synthesis of the most complex prostaglandin, PGF_2α. Access to this compound should not only render existing prostaglandin-based drugs more affordable, but will also facilitate the rapid exploration of chemical space around the ubiquitous five-membered ring motif. A concise new synthesis of the most complex of the Prostaglandins—diverse hormone-like chemical messengers—should make existing prostaglandin-based drugs cheaper and also facilitate other related syntheses. Prostaglandins are hormone-like chemical messengers that regulate a broad range of physiological activities, including blood circulation, digestion and reproduction^ 1 , 2 . Their biological activities and their complex molecular architectures have made Prostaglandins popular targets for synthetic organic chemists for over 40 years^ 3 , 4 . Prostaglandin analogues are widely used as pharmaceuticals and some, such as latanoprost, which is used to treat glaucoma^ 5 , 6 , have become billion-dollar drugs. Previously reported syntheses of these compounds are quite lengthy, and every chemical step costs time and energy, generates waste and is accompanied by material losses. Using a new bond disconnection, here we report a concise synthesis of the most complex prostaglandin, PGF_2α, with high levels of control of relative and absolute stereochemistry, and fewer steps. The key step is an aldol cascade reaction of succinaldehyde using proline organocatalysis to create a bicyclic enal in one step and an enantiomeric excess of 98%. This intermediate bicyclic enal is fully primed with the appropriate functionality for attachment of the remaining groups^ 7 . Access to this bicyclic enal will not only render existing prostaglandin-based drugs more affordable, but will also facilitate the rapid exploration of related chemical structures around the ubiquitous five-membered ring motif, such as potentially therapeutic prostaglandin analogues.
Lawrence G Raisz - One of the best experts on this subject based on the ideXlab platform.
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the role of Prostaglandins in the regulation of bone metabolism
Clinical Orthopaedics and Related Research, 1995Co-Authors: Hiroshi Kawaguchi, Carol C Pilbeam, John R Harrison, Lawrence G RaiszAbstract:Prostaglandins are likely to play an important role in the physiologic and pathologic responses of skeletal tissue. They are potent agonists that can stimulate and inhibit bone resorption and formation. In vivo, the major effect of exogenous Prostaglandins, particularly prostaglandin E 2 , is to stimulate resorption and formation. These effects appear to involve replication and differentiation of osteoclast and osteoblast precursors, and to be mediated at least in part by cyclic 3' 5' adenosine monophosphate. Prostaglandins can inhibit the activity of isolated osteoclasts, probably also by a cyclic 3' 5' adenosine monophosphate-mediated mechanism. Inhibition of collagen synthesis can be seen in cell and organ cultures and appears to be caused by a receptor selective for Prostaglandins of the F series and to involve activation of protein kinase C. Prostaglandin production by bone cells is regulated highly by mechanical forces, cytokines, growth factors, and systemic hormones. Prostaglandins also can amplify their own production. Regulation is associated with marked changes in the newly described inducible prostaglandin G/H synthase with less effect on the constitutive enzyme. Prostaglandins also may play a role in postmenopausal bone loss because estrogen deficiency, which increases bone turnover, can increase prostaglandin production in bone.
