Introduction:
While coumarin consists of no anticoagulant activity, it is converted to the natural anticoagulant dicoumarol via a number of species of fungi. This takes place as the result of the production of 4-hydroxycoumarin, then further (in the presence of naturally occurring formaldehyde) to the actual anticoagulant dicoumarol, a fermentation product and mycotoxin. This substance was responsible for the bleeding disease acknowledged historically as 'sweet clover disease' in cattle eating moldy sweet clover silage.
The Coumarin is employed in the pharmaceutical industry as a precursor molecule in the synthesis of a number of synthetic anticoagulant pharmaceuticals alike to dicoumarol, notably warfarin (Coumadin) and some even more potent Rodenticides which work by the similar anticoagulant procedure.
The drugs, cromolyn sodium (or cromolyn) and nedocromil are generally grouped altogether as Chromones (as well termed as cromoglycates). Strictly speaking, cromolyn is a Chromone, while nedocromil belongs to the structural class of pyranoquinolines. Both agents encompass a Chromone ring configuration (that is, one ring in nedocromil, two in cromolyn) and they share numerous clinical features.
Cromolyn was first introduced in Great Britain in the early year of 1970 for severe allergic asthma. Since then, recommendations for its utilization have shifted to milder asthma, where the agent gained greater acceptance. The Chromones are presently listed as alternate initial controller therapies for mild asthma in the national and international guidelines, however inhaled glucocorticoids (as well termed as inhaled corticosteroids or ICS) are the preferred agents. The low incidence of side effects compared to ICS is the leading reason some patients prefer Chromones over ICS.
Warfarin:
The Warfarin is a white crystalline compound, C19H16O4, utilized as a Rodenticide and as an anticoagulant. (As well acknowledged under the brand names Coumadin, Marevan, Jantoven, Lawarin, Waran and Warfant) is an anticoagulant. This is most likely to be the drug popularly termed to as a 'blood thinner', yet this is a misnomer, since it doesn't influence the thickness or viscosity of the blood. Rather, it acts on the liver to reduce the quantity of some key proteins in blood which allow blood to clot.
This was initially marketed as a pesticide against rats and mice and is still popular for this purpose; however more potent poisons like brodifacoum have since been developed. Some years after its introduction, warfarin was found to be efficient and comparatively safe for preventing thrombosis and embolism (that is, abnormal formation and migration of the blood clots) in numerous disorders. This was approved for the use as a medication in the early 1950s and has remained popular ever since; warfarin is the most broadly prescribed anticoagulant drug in North America.
In spite of its effectiveness, treatment by warfarin has some inadequacies. Many generally employed medications interact by warfarin, as do some foods (specifically fresh plant-based foods containing vitamin K), and its activity has to be monitored through blood testing for the international normalized ratio (INR) to make sure an enough yet safe dose is taken.
Fig: Structure of Warfarin
Warfarin is mainly employed to reduce the tendency for thrombosis or as secondary prophylaxis (that is, prevention of further episodes) in such individuals that have already made up a blood clot (thrombus). Warfarin treatment can help prevent formation of future blood clots and help decrease the risk of embolism (that is, migration of a thrombus to a spot where it blocks blood supply to the vital organ).
=> Racemic synthesis:
A classic manner of synthesizing racemic warfarin is via the base (or acid) catalyzed Michael condensation reaction of 4-hydroxycoumarin with benzalacetone either in the water or piperidine.
Fig: Synthesis of Racemic Warfarin
The method for this reaction is as shown below:
Fig: Mechanism for racemic warfarin
The result for this synthesis whenever carried out in water (4-8 h reflux) is usually 40 %. Higher results can be obtained via carrying out the reaction in methanol (20 h reflux), isolating the product made up and hydrolyzing with acid. Typical results are 93%.
There has been increasing interest in the pharmaceutical industry to substitute existing racemic drugs via their pure enantiomeric form because of the fact that one enantiomer often consists of a pharmacological profile superior to the race mate. In this case, S-warfarin is found to be 5 times more potent as the anticoagulant as compare to R-warfarin. The preparation of enantiomerically pure warfarin can be made up by the classical resolution of the race mate employing quinidine/quinine salts or chromatographic separation. Though, such methods are limited to the small scale preparations.
1) Asymmetric hydrogenation:
In the year 1996, researchers at the Dupont Merck pharmaceutical company build up a practical asymmetric synthesis of R- and S- warfarin starting from the racemate and employing DuPHOS-Rh(I) catalyzed hydrogenation (figure given below).
By using this process, S-warfarin was obtained in 83% enantiomeric excess (e.e), and R-warfarin in 86% e.e
Fig: Asymmetric Synthesis of R- and S-Warfarin
2) Hetero-Diels-Alder cycloaddition:
The prior synthesis utilized racemic warfarin as its starting material. A novel approach to asymmetric synthesis of warfarin by employing simpler starting materials was developed in the year 2001. It carries on by a hetero-Diels-Alder cycloaddition (figure shown below).
Fig: Asymmetric Synthesis of Warfarin by Hetero-Diels-Alder Cycloaddition
In the above reaction, S-warfarin was obtained in 95 % e.e
Sodium Cromoglycate:
Cromolyn, a synthetic compound, slows downs antigen-induced bronchospasms and, therefore, is employed to treat asthma and allergic rhinitis. Cromolyn is employed as an ophthalmic solution to treat conjunctivitis and is taken orally to treat the systemic mastocytosis and ulcerative colitis.
Cromolynn (USAN) (as well termed to as cromglicic acid (INN), cromoglycate (former BAN), or cromoglicate) is traditionally illustrated as a mast cell stabilizer, and is generally marketed as the sodium salt sodium cromoglicate or cromolyn sodium. This drug prevents the discharge of inflammatory chemicals like histamine from the mast cells.
Due to their convenience (and apparent safety), leukotriene receptor antagonists have mainly substituted it as the non-corticosteroid treatment of choice in the treatment of asthma. Cromoglicic acid needs administration four times daily, and doesn't give additive benefit in combination by inhaled corticosteroids.
Fig: Sodium Cromoglycate (5,5′-(2-hydroxypropane-1,3-diyl)bis(oxy)bis(4-oxo-4H-chromene-2-carboxylic acid)
Tutorsglobe: A way to secure high grade in your curriculum (Online Tutoring)
Expand your confidence, grow study skills and improve your grades.
Since 2009, Tutorsglobe has proactively helped millions of students to get better grades in school, college or university and score well in competitive tests with live, one-on-one online tutoring.
Using an advanced developed tutoring system providing little or no wait time, the students are connected on-demand with an expert at www.tutorsglobe.com. Students work one-on-one, in real-time with a tutor, communicating and studying using a virtual whiteboard technology. Scientific and mathematical notation, symbols, geometric figures, graphing and freehand drawing can be rendered quickly and easily in the advanced whiteboard.
Free to know our price and packages for online chemistry tutoring. Chat with us or submit request at [email protected]
tutorsglobe.com anamalous nature of fluorine assignment help-homework help by online halogen family tutors
Theory and lecture notes of Price level and Inflation all along with the key concepts of Price level and inflation, Consumer Price Index, Inflation Rate, Paasche index and Laspeyres index. Tutorsglobe offers homework help, assignment help and tutor’s assistance on Price level and inflation.
tutorsglobe.com proteins assignment help-homework help by online cell membrane tutors
Free CLEP Study Guide, CLEP Test Papers, CLEP Practice papers, CLEP Test pattern and general information, Find CLEP exam information and resource, material free at Tutorsglobe.com
Application of the Iso-quinoline Ring System tutorial all along with the key concepts of Papaverine, Synthesis of Papaverine, Morphine, Isoquinolines and Parkinson's disease
Avail first-class Introduction to Developmental Biology Assignment Help with 24x7 support of qualified tutors to score high at feasible prices.
Metazoa-Origin and Evolution tutorial all along with the key concepts of Levels of body organization, Characteristics of metazoa, Developmental patterns in metazoa, Body cavity and Coelom, Cephalisation and segmentation, Origin and evolution of metazoa
Throughout the conduction of BU205, self oscillations are generated in the LOT. Line output transformer operates on step-up and step-down techniques.
tutorsglobe.com dark reactions assignment help-homework help by online cyclic and noncyclic photophosphorylation tutors
tutorsglobe.com copper sulphate assignment help-homework help by online compound tutors
types of solution tutorial all along with the key concepts of types of solution according to their saturation ratio, types of solutions as suspensions and colloids, ways of deducing concentration of solution
reactions of hydrocarbons tutorial all along with the key concepts of reaction with bromine, reaction with concentrated sulphuric acid, reaction with potassium permanganate, physical properties of hydrocarbons, chemical properties of hydrocarbons
The Angiosperms tutorial all along with the key concepts of Common features of Angiosperms, Adaptive Features, Monocotyledoneae and Dicotyledoneae
Reflection of Light tutorial all along with the key concepts of Concept of Light, Rectilinear Propagation of Light, Shadows, Eclipses, Pinhole Camera and Reflection of Light at Plane Surfaces
Wave motion tutorial all along with the key concepts of Types of Waves, Transverse wave, Longitudinal wave, Propagation of Waves, Representation of Wave Motion, Relation between Wave Velocity, Frequency and Wavelength, Phase Difference, Progressive Waves
1954971
Questions Asked
3689
Tutors
1455408
Questions Answered
Start Excelling in your courses, Ask an Expert and get answers for your homework and assignments!!