Grant: Research Tools and Instruments - Category 1 (<$150,000)
Queen's University
$122,888.00
Supercritical fluid chromatography in the synthesis of chiral pharmaceuticals, fine chemicals and organic materials
EF 2012-13
Résumé
) Chirality is a property that many molecules possess, and it is often compared to handedness since chiral molecules are identical except for being right- or left-handed. Chirality is widely prevalent in nature: from the spiral of snail shells to the helical twist in DNA. Nineteen of the twenty essential amino acids are chiral, and in mammalian species, these exist only in their left-handed forms. Since amino acids are the building blocks of peptides, proteins, and enzymes, the biochemical machinery of the body relies on chiral interations.
) A classic example of the significance of chirality in living systems is Thalidomide, prescribed to prevent morning sickness in the late 1950's. Like many other pharmaceuticals, Thalidomide is chiral. Although the right-handed form is effective at curing morning sickness and is otherwise completely harmless, the left-handed form, causes severe birth defects. Since Thalidomide was sold as a mixture of the R and S forms, mothers taking as little as one pill between the 20th and 36th day of conception gave birth to babies with severe birth defects. Penicillin also relies on chirality for activity since the righted handed form mimics the amino acids in the cell walls of bacteria, while the other is ineffective.
) Nine out of the top ten drugs on the market are chiral, including Lipitor ($16 billion p.a.), Zocor ($5.9 billion p.a.), Plavix ($5.0 billion p.a.) and Nexium ($4.8 billion p.a.). Unfortunately, methods to access chiral compounds as the right handed or left handed form are not simple. Traditional approaches revolve around separation of the two forms, but this is costly and wasteful since the ""wrong"" form, which is 50% of the mixture by definition, is discarded. Thus many researchers are looking at ways of preparing one form or the other via a de novo selective synthesis (the Nobel prize was given in 2001 for this). In order to do this, a way to analyze the selectivity of the reaction is essential to permit optimization. With four department members actively involved in this area, we request a dedicated instrument to permit us to analyze chiral compounds we produce and asses how selective our transformations are. This is absolutely essential for our research.
Programme
Research Tools and Instruments - Category 1 (<$150,000)
Bénéficiaire
Emplacement
Ontario, Canada
Type de bénéficiaire
Academia
Type
Grant
Source
NSERC's Awards Data
Tel que publié
Application id
440053-2013
Name nom
Crudden, Cathleen
Department département
Chemistry
Organization id
29
Institution établissement
Queen's University
Province en
Ontario
Province fr
Ontario
Country en
CANADA
Country fr
CANADA
Fiscal year exercice financier
2012
Competition year année de concours
2013
Award amount
122888
Program id
EQPEQ
Program name en
Research Tools and Instruments - Category 1 (<$150,000)
Program name fr
Outils et instruments de recherche - catégorie 1 (<150 000$)
Group en
Discovery grants programs
Group fr
Programmes de subventions à la découverte
Committee code
1504
Committee name en
Chemistry
Committee name fr
Chimie
Area of application code
1202
Area of application group en
Advancement of knowledge
Area of application group fr
Avancement des connaissances
Area of application en
Physical sciences
Area of application fr
Sciences physiques
Research subject code
3703
Research subject group en
Organic chemistry
Research subject group fr
Chimie organique
Research subject en
Organic syntheses
Research subject fr
Synthèses organiques
Partie
1
Nb partie
1
Application title
Supercritical fluid chromatography in the synthesis of chiral pharmaceuticals, fine chemicals and organic materials
Keyword
NSERC
Application summary
) Chirality is a property that many molecules possess, and it is often compared to handedness since chiral molecules are identical except for being right- or left-handed. Chirality is widely prevalent in nature: from the spiral of snail shells to the helical twist in DNA. Nineteen of the twenty essential amino acids are chiral, and in mammalian species, these exist only in their left-handed forms. Since amino acids are the building blocks of peptides, proteins, and enzymes, the biochemical machinery of the body relies on chiral interations.
) A classic example of the significance of chirality in living systems is Thalidomide, prescribed to prevent morning sickness in the late 1950's. Like many other pharmaceuticals, Thalidomide is chiral. Although the right-handed form is effective at curing morning sickness and is otherwise completely harmless, the left-handed form, causes severe birth defects. Since Thalidomide was sold as a mixture of the R and S forms, mothers taking as little as one pill between the 20th and 36th day of conception gave birth to babies with severe birth defects. Penicillin also relies on chirality for activity since the righted handed form mimics the amino acids in the cell walls of bacteria, while the other is ineffective.
) Nine out of the top ten drugs on the market are chiral, including Lipitor ($16 billion p.a.), Zocor ($5.9 billion p.a.), Plavix ($5.0 billion p.a.) and Nexium ($4.8 billion p.a.). Unfortunately, methods to access chiral compounds as the right handed or left handed form are not simple. Traditional approaches revolve around separation of the two forms, but this is costly and wasteful since the ""wrong"" form, which is 50% of the mixture by definition, is discarded. Thus many researchers are looking at ways of preparing one form or the other via a de novo selective synthesis (the Nobel prize was given in 2001 for this). In order to do this, a way to analyze the selectivity of the reaction is essential to permit optimization. With four department members actively involved in this area, we request a dedicated instrument to permit us to analyze chiral compounds we produce and asses how selective our transformations are. This is absolutely essential for our research.