Grant: Discovery Grants Program - Individual
Brock University
$83,000.00
Program in chemoenzymatic asymmetric synthesis: amaryllidaceae and morphine alkaloids, chiral synthons, and new reagents for asymmetric synthesis
FY 2011-12
Summary
The overall focus of our program is the development of efficient protocols for asymmetric synthesis of compounds of medicinal importance. The investigation of new methods of environmentally benign manufacturing or ""green"" synthesis benefits from the combination of biological methods with sound strategic planning of chemical pathways. The proposed research represents a well-integrated approach to two important groups: the morphine alkaloids and the Amaryllidaceae alkaloids, as well as medicinally useful derivatives of both. In addition, new biotransformations will be pursued in order to provide chiral building blocks and a chiral version of the Burgess reagent will be applied to the total synthesis of balanol.
Our well-integrated program follows the following objectives: (A) Biotransformations: (i) Whole-cell fermentations of arenes generate new chiral starting materials for manufacturing of pharmaceuticals. (ii) Yeast and fungal strains are employed in the synthesis of catalysts and C-14 oxygenated derivatives of morphine, respectively. (B) Two syntheses of anti-tumor agent pancratistatin are proposed. In addition, new strategies are presented for the generation of more bioavailable analogs of Amaryllidaceae constituents. (C) New approaches to morphine alkaloids are presented along with a short synthesis of oxycodone, an important pain medicine.
(D) Serendipitous discoveries in asymmetric synthesis led to new reactive options for the Burgess reagent. Its chiral versions will be investigated in the synthesis of amino alcohols, important linkers in drug design. (E) These efforts culminate in the total syntheses of balanol, a phosphokinase C inhibitor, and of Tamiflu, an important antiviral agent.
Overall, this proposal addresses focused investigations in asymmetric synthesis driven by the use of biocatalytic methods for a greater ""green"" component. Highly qualified personnel at undergraduate, graduate, and postdoctoral levels will be trained in biocatalysis and synthesis for the Canadian pharmaceutical sector and marketable medicinal agents will be prepared.
Program
Discovery Grants Program - Individual
Recipient
Location
Ontario, Canada
Recipient Type
Academia
Type
Grant
Source
NSERC's Awards Data
As published
Application id
262022-2008
Name nom
Hudlicky, Tomas
Department département
Chemistry
Organization id
22
Institution établissement
Brock University
Province en
Ontario
Province fr
Ontario
Country en
CANADA
Country fr
CANADA
Fiscal year exercice financier
2011
Competition year année de concours
2008
Award amount
83000
Program id
RGPIN
Program nane en
Discovery Grants Program - Individual
Program name fr
Programme de subventions à la découverte - individuelles
Group en
Discovery grants programs
Group fr
Programmes de subventions à la découverte
Committee code
24
Committee name en
Inorganic & Organic Chemistry
Committee name fr
Chimie inorg. et org.
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
4
Nb partie
5
Application title
Program in chemoenzymatic asymmetric synthesis: amaryllidaceae and morphine alkaloids, chiral synthons, and new reagents for asymmetric synthesis
Keyword
NSERC
Application summary
The overall focus of our program is the development of efficient protocols for asymmetric synthesis of compounds of medicinal importance. The investigation of new methods of environmentally benign manufacturing or ""green"" synthesis benefits from the combination of biological methods with sound strategic planning of chemical pathways. The proposed research represents a well-integrated approach to two important groups: the morphine alkaloids and the Amaryllidaceae alkaloids, as well as medicinally useful derivatives of both. In addition, new biotransformations will be pursued in order to provide chiral building blocks and a chiral version of the Burgess reagent will be applied to the total synthesis of balanol.
Our well-integrated program follows the following objectives: (A) Biotransformations: (i) Whole-cell fermentations of arenes generate new chiral starting materials for manufacturing of pharmaceuticals. (ii) Yeast and fungal strains are employed in the synthesis of catalysts and C-14 oxygenated derivatives of morphine, respectively. (B) Two syntheses of anti-tumor agent pancratistatin are proposed. In addition, new strategies are presented for the generation of more bioavailable analogs of Amaryllidaceae constituents. (C) New approaches to morphine alkaloids are presented along with a short synthesis of oxycodone, an important pain medicine.
(D) Serendipitous discoveries in asymmetric synthesis led to new reactive options for the Burgess reagent. Its chiral versions will be investigated in the synthesis of amino alcohols, important linkers in drug design. (E) These efforts culminate in the total syntheses of balanol, a phosphokinase C inhibitor, and of Tamiflu, an important antiviral agent.
Overall, this proposal addresses focused investigations in asymmetric synthesis driven by the use of biocatalytic methods for a greater ""green"" component. Highly qualified personnel at undergraduate, graduate, and postdoctoral levels will be trained in biocatalysis and synthesis for the Canadian pharmaceutical sector and marketable medicinal agents will be prepared.
