employment - Planta Analytica

advertisement
Jan A. GLINSKI, Ph.D.
8 Warwick Road
New Fairfield, CT 06812
home: (203) 746-1407
glinskijan@earthlink.net
EXECUTIVE SUMMARY: A very broad background in natural sciences
encompassing medicinal/organic chemistry, natural products isolation and
characterization, protein purification, chromatographic methods, and spectral
characterization methods used in support of HTS. Thirteen years of R&D experience
comprising all stages of drug discovery and drug development. Experience with
laboratory staff and project management. Initiated, organized and lead international and
multidisciplinary effort to discover new therapeutically useful natural products.
Successful implementation of novel separation technologies. Consulting experience.
EDUCATION:
1979 - Ph.D. in organic chemistry. Thesis: "Total Synthesis of Cassipurine".
Advisor: Prof. J. T. Wrobel, University of Warsaw.
1974 - M.S. in organic chemistry. Thesis: "Structure - Light Absorption
Relationship for Model Purple Photographic Dyes", U. of Warsaw, Poland.
POST-DOCTORAL STUDIES:
1985 – 1987: Research Scientist/Associate, Georgia Institute of Technology, School
of Chemistry. Advisors: Profs. James C. Powers and Sheldon W. May.
 Syntheses of multifunctional quaternary amines directed at the reactivation of
acetylcholinesterase inhibited with the nerve gas Soman.
 Synthesis of isocoumarin derivatives as potential drugs against emphysema and
kinetic determination of their inhibitory properties of human leukocyte elastase
(HLE).
1984 – 1985: Research Scientist, Georgia Institute of Technology, School of
Chemistry. Advisor: Dr. Leon H. Zalkow.
 Structure elucidation of novel natural products. Enhancement of therapeutic
properties by chemical modifications.
 Preparation of novel potent and water-soluble prodrugs of Taxol.
 Application of droplet countercurrent chromatography (DDC) for isolating natural
products and for separating complex mixtures of isomeric alkaloids.
 Crystal X-ray analysis used to elucidate unusual structural features in the
crystals of secopyrrolizidine alkaloids with partial N---C=O trans-annular bond.
1981 – 1982: Postdoctoral Fellow, University of Georgia, Athens.
Advisor: Dr. S. W. Pelletier.

Isolation, structure elucidation and structural modification of the diterpenoid
alkaloids from Delphinium and Aconitum genera.
1
EMPLOYMENT:
2000-present: Ceres-Eco, LLC, president
2002-present: Planta Analytica, owner.
1987 - 2000, Senior Scientist/Principal Scientist, Departments of Medicinal
Chemistry,
Analytical Sciences, Pharmaceutics and Clinical Research.
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut.
Analytical:
 Advisory support to Medicinal Chemistry in analytical and separation methods
(including recommendation for purchasing new instrumentation).
 Managed routine and exotic research projects directed at isolation of active
components of mixtures, active contaminants, and also did troubleshooting of
anomalous phenomena in screening.
 Developed automated LC/MS systems for high throughput purification and
identification of compounds from combinatorial chemistry.
 Developed Supercritical Fluid Chromatography (SFC) for analysis and
purification of combinatorial libraries.
 Extensively used HPLC for a wide variety of routine and exotic research projects such
as: separation of active components of mixtures, developing protocols for
purification of compounds from parallel synthesis and profiling of hits from
screening.
 Developed and applied Countercurrent Chromatography methods for isolation of
trace quantities of active and labile natural products.
 Developed chiral HPLC methods for analysis and purification of enantiomers.
 Isolated and structurally characterized minor contaminants of BI drugs.
Natural Products:
 Managed Natural Products Program and Laboratory; coordinated all stages of
high throughput screening of plant and microbial extracts.
 Initiated an international multicenter-screening program for natural products.
Developed and implemented protocols for extraction, bioassay-guided
fractionation, analysis and elimination of the interference caused by "false
positives".
 Developed state-of-the-art applications of countercurrent chromatography to
non-destructive isolations of active components.
 Structure elucidation of active components of microbial and plant extracts;
isolation of several potent natural immunosuppressants in conjunction with
various research projects.
 Discovered a new facet of a general anti-infective mechanism of plant defenses
that led to a novel environmentally friendly plant protection product (patent
pending, out-licensed technology).
2
Antioxidants:
 In close collaboration with pharmacology labs conducted experiments that
defined antioxidant/anti-inflammatory properties of hypericin (St. John’s Wort)
and chlorophyll with its derivatives, suggesting an important dietary role for the
latter compound.
 Conducted extensive in vivo experimentation with antioxidant inhibition of
oxidative stress in the neutrophil- and xanthine oxidase-driven inflammatory
responses.
Proteins:
 Isolation and purification of recombinant HIV reverse transcriptase for the
Viramune® project.
 Purification of cell adhesion monoclonal antibodies.
 Preparation of small molecule-protein conjugates for immunization.
 Chemical derivatization of monoclonal antibodies to eliminate antigenicity in
vivo.
Clinical Research:
 Development of early Phase I and Phase II protocols for experimental pulmonary
drugs. .
 Basic elements of clinical trial organization.
 Writing of the Clinical Investigator’s Brochure (BILL 284).
 Presentation to upper management.
 Analysis of data from trials of a novel leukotriene receptor inhibitor.
 Literature searches for explaining unexpected side effects.
1979 –1980: Research Scientist, University of Warsaw, Poland. Advisor: Dr. Jerzy
T. Wrobel
 Stereo specific synthesis of sulfur-containing alkaloids.
 Syntheses of the sulfur-substituted furan, pyrrole, and pyrrolizidine synthones.
1994-1995: Scientific consultant to Procept, Boston, MA.
1993-2000: Scientific consultant to MicroFlo, Co., a BASF subsidiary.
2001-2002: Consultant to Microsource Botanica, Inc.
2002-present: Consultant to Muro Pharmaceutical (subsidiary of Astra Pharm.)
2002-present: Consultant to Proquisa Agrochemicals/
1995-present: Reviewer for Journal of Natural Products.
AWARDS:
1980 - Award of the Secretary of Polish Academy of Science.
1969 - Winner of the National Olympic Competition in Chemistry.
3
ADVANCED MANAGEMENT TRAINING:
BIPI internal training: Strategic Communication, Project Management, Ideas in Action,
Effective Management Practices, Leadership and Organizational Teamwork,
Developing Team Effectiveness, Systematic Team Work.
PROFESSIONAL MEMBERSHIP:
American Society of Pharmacognosy, American Chemical Society, Society for
Industrial Microbiology, American Society of Microbiology, American Association for
Advancement in Science.
4
Jan A. GLINSKI, Ph.D.
Publications
1. "Total Synthesis of Cassipurine, an Alkaloid of Rhizophoraceae", J.T. Wrobel, J.A.
Glinski, Can. J. Chem. 59, 1101 (1981).
2. "Origin of Oxonitine, a Potassium Permanganate Oxidation Product of Aconitine",
S.W. Pelletier, J.A. Glinski, N.V. Mody, J. Am. Chem. Soc. 104, 4676 (1982).
3. "Unusual Hetisine Rearrangement Products" S.W. Pelletier, J.A. Glinski, K. I.
Varughese, J.A. Maddry, N.V. Mody, Het. 20, 413 (1983).
4. "The Diterpenoid Alkaloids of Delphinium tatsienense Franch", S.W. Pelletier,
J.A. Glinski, B.S. Joshi, Szu-ying Chen, Het. 20, 1347 (1983).
5. "The Structure of Tatsiensine, a Novel C19-Diterpenoid Alkaloid from Delphinium
tatsienense Franch", J.A. Glinski, B.S. Joshi, Szu-ying Chen, S.W. Pelletier,
Tet. Lett. 25, 1211 (1984).
6. "Deltatsine, a New C19-Diterpenoid Alkaloid from Delphinium tatsienense Franch"
B.S. Joshi, J.A. Glinski, Szu-ying Chen, S.K. Srivastava, S.. W. Pelletier,
Het. 20, 2037 (1984).
7. "Synthesis of Pyrrolizidine Alkaloids: Indicine, Intermedine, Lycopsamine, and
Analogues and Their N-Oxides. Potential Antitumor Agents", L.H. Zalkow, J.A.
Glinski, L.T. Gelbaum, L.S. McGowan, T.J. Fleischmann, M.M. Gordon,
J. Med. Chem. 28, 687 (1985).
8."Retronecine and Heliotridine, C8H13NO2: Diastereomeric Pyrrolizidine Bases",
L.T. Gelbaum, J.A. Glinski, D. VanDerveer, L.H. Zalkow, Acta Cryst.
C41, 13454 (1985).
9. "Synthesis of Heliotridine and Related Alkaloids", J.A. Glinski, L.H. Zalkow,
Tet. Lett. 26, 2857 (1985).
10. "Diastereoisomeric Epoxides of Heliotridine and Retronecine, C8H13NO3",
J.A. Glinski, D. VanDerveer, L.H. Zalkow, Acta Cryst. C42, 1237 (1986).
11. "Molecular Structure of 1,2-oxy-2-bromotrachelanthamidine, C8H12NO3Br",
J.A. Glinski, D. VanDerveer, L.H. Zalkow, Acta Cryst. C42, 1237 (1986).
12. "The Structures of Four New C19-Diterpenoid Alkaloids from Aconitum forrestii
5
Stapf", S.W. Pelletier, B.S. Joshi, Q.-P. Jiang, S.W. Pelletier, Het. 27, 185 (1988).
13. "Hetisine Derivatives, Part 1: Acetylation and Oxidation of Hetisine", J.A. Glinski,
B.S. Joshi, Q. P. Jiang, S.W. Pelletier, Het. 27, 185 (1988).
14. "Hetisine Derivatives, Part 2: Novel Rearrangement of 11-Dehydrohetisine and
2,11-Didehydrohetisine", B.S. Joshi, J.A. Glinski, K.I. Varughese, S.W. Pelletier,
Het. 27, 195 (1988).
15. "Hetisine Derivatives, Part 3. Rearrangement of 11-Acetyl-2,13-di-dehydrohetisine
and 13-Dehydro-2,11-diacetylhetisine", Q.-P. Jiang, J.A. Glinski, B.S. Joshi,
J.A. Maddry, M.G. Newton, S.W. Pelletier, Het. 27, 9925 (1988).
16. "Macrocyclic Pyrrolizidine Alkaloids from Senecio anononymus. Separation of a
Complex Alkaloid Extract Using Droplet Countercurrent Chromatography",
L.H. Zalkow, C.F. Asibal, J.A. Glinski, S.J. Bonetti, L.T. Gelbaum,
D. VanDerveer, G. Powis, J. Nat. Prod. 31, 1520 (1988).
17. "Semisynthetic Pyrrolizidine Alkaloid N-Oxide Antitumor Agents. Esters of
Heliotridine", L.H. Zalkow, J.A. Glinski, L.T. Gelbaum, D. Moore, D. Melder,
G. Powis, J. Med. Chem. 31, 1520 (1987).
18. "Anonamine, C19H27NO7; Neosenkirkine, C19H27NO6; Hydroxysenkirkine,
C19H27NO7.MeOH. Macrocyclic Secopyrrolizidine Alkaloids from Senecio
anonymus Wood", J.A. Glinski, C.F. Asibal, D. VanDerveer, L.H. Zalkow,
Acta Cryst. C44, 1593 (1988).
19. "Pyrrolizidine Alkaloids from Cynoglossum creticum. Synthesis of Pyrrolizidine
Alkaloids Echinatine, Rinderine, and Analogs", C.F. Asibal, J.A. Glinski,
L.T. Gelbaum, L.H. Zalkow, J. Nat. Prod., 52, 109 (1989).
20. "Synthesis of Congeners and Prodrugs. 3. Water-Soluble Prodrugs of Taxol
with Potent Antitumor Activity", H.M. Deutsch, J.A. Glinski, M. Hernandez,
R.D. Haugwitz, V.L. Narayanan, M. Suffness, L.H. Zalkow, J. Med. Chem.
32, 788 (1989).
21. "The Structure and Partial Synthesis of Delelatine, an Alkaloid from Delphinium
Species", S.A. Ross, H.K. Desai, B.S. Joshi, S.K. Srivastava, J.A. Glinski,
S.-Y. Chen, S.W. Pelletier, Phytochemistry 27, 3719 (1988).
22. "Effect of the 7-Amino Substituent on the Inhibitory Potency of Mechanism-Based
Isocoumarin Inhibitors for Porcine Pancreatic and Human Neutrophil Elastases:
A 1.85-Å X-ray Structure of the Complex between Porcine Pancratic Elastase
and 7-[(N-Tosylphenylalanyl)amino]-4-chloro-3-methoxyisocoumarin",
M. Hernandez, J.C. Powers, J.A. Glinski, J. Oleksyszyn, J. Vijayalakshmi,
6
E.F. Meyer, J. Med. Chem. 35, 1121-1129 (1991).
23. "Screening Natural Products. Bioassay-Directed Isolation of Active Components.",
J.A. Glinski, G.O. Caviness, J.R. Mikell, J. Liq. Chrom. 13, 3625 (1990).
24. "Tatsirine, A Diterpenoid Alkaloid from Delphinium tatsienense Franch", X.
Zhang,
J.K. Snyder, B.S. Joshi, J.A. Glinski, S.W. Pelletier Heterocycles 31, 1879 (1990).
25. "Production and Purification of Recombinant HIV-1 and HIV-2 Reverse
Transcriptase: Preparation of Both Homodimeric and Heterodimeric Forms",
T.C. Warren, J.J. Miglietta, J.M. Rose, L. Kopp, K. Lubbe, J.C. Wu, K.A. Cohen,
J.A. Glinski, D.E.H. Palladino, G.O. Caviness, G.C. Chow, S.L. Rogers, P. Farina,
P.M. Grob, Biochem. (1992).
26. "Centrifugal Partition Chromatography in Assay-guided Isolation of
Immunosuppressive Components of Tripterygium wilfordii", J.A. Glinski,
G.O. Caviness, Chapter 6, pp. 133-165, in Handbook of Centrifugal Partition
Chromatography, ed. A. Foucault, M. Dekker (1995).
27. "Inactivation of Cell Surface Receptors by Pheophorbide A, a green pigment
isolated from Psychotria acuminata", J.A. Glinski, E. David, T.C. Warren,
G. Hansen, S.F. Leonard, P. Pitner, S. Pav, R. Arvigo, M.J. Balick, E. Panti,
P.M. Grob, Photochem. Photobiol. 62, 144-150 (1995).
28. “Anti-inflammatory and antioxidant properties of hypericin”, J.A. Glinski,
Diane Thome, Genus Possanza, Randall Barton, (in preparation).
29. “Anti-inflammatory and antioxidant properties of hematin, chlorophyll derivatives,
and phtalocyanins”, J.A. Glinski, Diane Thome, Genus Possanza, Randall Barton,
(in preparation).
30. Anti-inflammatory and antioxidant properties of dyes of diverse structures”,
J.A. Glinski, Diane Thome, Genus Possanza, Randall Barton, (in preparation).
Patents
1. U.S. Patent 5,157,049 "Method of Treating cancers Sensitive to Treatment
with Water Soluble Derivatives of Taxol", Oct.20, 1992, R.D. Haugwitz, L.H.
Zalkow, J.A. Glinski, H.M. Deutsch, V.L. Narayanan.
2. U.S. Patent 5,089,633, "Substituted Isocoumarins", Feb. 18, 1992, J.C. Powers,
C.-M. Kam, J. Oleksyszyn, J.A. Glinski, M. Hernandez.
7
3. U.S. Patent 5,206,371 "Quaternary Pyridinium Compounds", Apr. 27, 1993,
J.C. Powers, S.W. May, M.A. Hernandez, S. Thornton, J.A. Glinski.
4. U.S. Patent 5,180,831 "Quaternary Pyridinium Compounds", Jan. 19, 1993,
J.C. Powers, S.W. May, M.A. Hernandez, S. Thornton, J.A. Glinski.
5. U.S. Patent 5,290,942 "Quaternary Pyridinium Compounds and Uses Therefor",
March 1, 1994, J.C. Powers, S.W. May, M.A. Hernandez, S. Thornton, J.A. Glinski.
6. U.S. Patent 5,324,648, "Substituted Isocoumarins as Serine Protease Inhibitors
and Anti-inflammatory Agents", June 28, 1994, J.C. Powers, C.-M. Kam,
J. Oleksyszyn, J.A. Glinski, M. Hernandez.
7. Canadian Patent 1,330,436 "Water Soluble, Antineoplastic Derivatives of Taxol",
June 26, 1994, R.D. Haugwitz, L.H. Zalkow, J.A. Glinski, H.M. Deutsch, V.L.
Narayanan.
8. US Patent 6,303,589 “Pentacyclic triterpenes”. J. A. Glinski, K. L. Branly,
Oct. 16, 2001.
Papers Presented
1. Polish-Czechoslovakian Symposium on Natural Products, Warsaw, June 1978,
J.T. Wrobel, J.A. Glinski, "Synthesis and Reactions of 1,2-Didehydropyrrolizidine".
2. Polish-Czechoslovakian Symposium on Natural Products, Warsaw, July 1980,
J.T. Wrobel, J.A. Glinski, "Conversion of 1,2-Epoxypyrrolizidines to
1,2-Epithiopyrrolizidines. Stereo-Controlled Cleavage of the Oxiirane Ring".
3. IUPAC 12th International Symposium on Chemistry of Natural Products, Spain,
Aug. 1980, J.T. Wrobel, J.A. Glinski, "Synthesis of Cassipurine".
4. Third IUPAC Symposium on Organic Synthesis, Madison, WI, 1980, J.T. Wrobel,
J.A. Glinski, "Total Synthesis of Cassipurine".
5. Eighth International Symposium on Medicinal Chemistry, Uppsala, Sveden,
Aug. 27-31, 1984, L.H. Zalkow, L.T. Gelbaum, J.A. Glinski, "Semisynthetic
Pyrrolizidine Alkaloid Antitumor Agents".
6. 36th Southern Regional meeting, ACS, Raleigh, NC, October 24-26 1984,
J.A. Glinski, L.H. Zalkow, "Synthesis of Heliotridine and Heliotridine Ester
Alkaloids from Retronecine".
7. American Society for Pharmacology and Experimental Therapeutics, ACS
Symposium, Boston, MA, Aug. 18-22 1985, L.H. Zalkow, J.A. Glinski,
8
T. Fleishman, T. Fortune, "Semisynthetic Pyrrolizidine Alkaloid Antitumor
Agents".
8. 191st National ACS Meeting, New York, April 1986, L.H. Zalkow, J.A. Glinski,
G. Powis,"Semisynthetic Pyrrolizidine Alkaloid Antitumor Agents. Heliotridine
derivatives".
9. 8th Atlanta Chromatography Symposium, Atlanta, GA, June 4 1986, C.F. Asibal,
J.A. Glinski, L.H. Zalkow, "Use of Droplet Countercurrent Chromatography for
Separation of Isomeric Pyrrolizidine Alkaloids".
10. Meeting of American Society of Biochemistry, Philadelphia, Aug. 1987,
J.C. Powers, M. Hernandez, J.A. Glinski, C.-M. Kam, J. Oleksyszyn,
"Mechanism-Based Isocoumarin Inhibitors for Human Leukocyte Elastase
and Cathepsin G".
11. International Congress on Natural Products Research, Park City, UT, July 1988,
L.H. Zalkow, C.F. Asibal, J.A. Glinski, S.J. Bonetti, L.T. Gelbaum, D. VanDerveer,
G. Powis, "Macrocyclic Pyrrolizidine Alkaloids from Senecio anonymus".
12. Invited lecture. National Cancer Institute, Frederick, MD, Feb. 9 1989, J.A. Glinski
"Joys and Pitfalls of High Capacity Screening".
13. 50th Meeting of the American Society of Pharmacognosy, San Jose, Puerto Rico,
Aug. 1989, J.A. Glinski, G. Chow, M. Skoog, M. Matteo "Inhibition of Elastase by
Pentacyclic Triterpenes".
14. Proceedings of 1989 Medical Defenses Bioscience Review, Washington, DC,
Aug. 1989, J.C. Powers, M. Hernandez, J.A. Glinski, K. Black "Disubstituted
Pyrdinium Salts as Reactivators of Soman-Inactivated Acetylcholinesterase".
15. Invited lecture. Third International Colloquium on Centrifugal Partition
Chromatography, San Mateo,CA, June 21-22 1990, J.A. Glinski, G.O.
Caviness, J.R. Mikell "Screening Natural Products. Bioassay-directed
Isolation of Active Components".
16. Innovations in Antiviral Development and Detection of Viral Infections,
Philadelphia,Nov.14-15, 1990, T.C. Warren, J.J. Miglietta, J.M. Rose, K. Lubbe,
S.L. Rogers, G.O. Caviness, J.A. Glinski, C-K. Shih, G.C. Chow, K.D. Hargrave,
K.K. Grozinger, J. Adams, P.R. Farina, P.M. Grob, "Preparation of Recombinant
HIV-1 and HIV-2 Reverse Transcriptase: Specificity of Inhibition by a Novel, Nonnucleoside RT Inhibitor, BI-RG-587.
17. 201st ACS Meeting, Atlanta, April 1991, H.M. Deutsch, L.L. Ernhart, J.A. Glinski,
M.A. Hernandez, R.D. Haugwitz, V.L. Narayanan "Water Soluble Prodrugs of The
Benzene Maleimide Photoadduct Mitindomide as Potential Antitumor Agents".
9
18. 201st ACS Meeting, Atlanta, April 1991, M.A. Hernandez, S.S. Thornton,
J.A. Glinski, B.D. White, Y-Y. Chen, S.W. May, J.C. Powers, "Prophylactic
Agents and Reactivators Against Poisoning by Soman and Tabun".
19. International Research Congress on Natural Products, American Society of
Pharmacognosy, Chicago, July 21-26, 1991, J.A. Glinski, P.M. Grob,
T.C. Warren, E. David, J. Proudfoot, . Hansen, S.F. Leonard "Inactivation of
Cell Surface Receptors by Pheophorbide A and Pyropheophorbide A, Natural
Products Isolated from Leaves of Psychotria acuminata.
20. Invited lecture. New England Chromatography Council Symposium, June 26,
1992, Danbury, CT, "Use of Centrifugal Partition Chromatography for the
Isolation of Active Principles from the Chinese Medicinal Plant Tripterygium
wilfordii. G.O. Caviness, J.A. Glinski.
21. Second Joint Meeting of the Phytochemical Societes of Europe/North America,
August 8-12, 1992, Miami Beach, FL, "Use of Centrifugal Partition
Chromatography
for the Isolation of Triptolide and Tripdiolide from the Chinese Medicinal Plant
Tripterygium wilfordii, G.O. Caviness, J. Ksiazek, R. Barton, J.A. Glinski.
22. Thirty fourth Meeting of the American Society of Pharmacognosy, July 18-22,
1993, San Diego CA, "Bioassay-guided isolation of Triptolide from Tripterygium
wilfordii and its biological properties" J.A. Glinski, G.O. Caviness, J. Ksiazek,
M.M.
O'Neill, D. Fortugno-Erikson, R.A. Jejer, J.R. Mikell, K.G. Grozinger, T.P. Parks,
R. Mucci, R.W. Barton, S.D. Marlin, P.E. Lipsky, X. Tao. 5.
23. Invited lecture. Hans Knoll Research Institute, Jena, Germany, July 22, 1993,
J.A Glinski, “Significance of plant-derived non-specific enzyme inhibitors for
antimicrobial plant defenses”.
24. Invited lecture. Second Annual Conference of the Clinical and Commercial
Benefits
of Medicinal Plants, Washington, D.C., September 11-12, 1995, "Plant Secondary
Metabolites: Their Natural Role versus Responses in biological Testing" J. A.
Glinski
10
Download