Transcript Vincristine - University of Notre Dame

Vincristine
Michael Doe
CHEM 23202
Overview
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I.
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Physical Properties
Synthesis
Characterization
History and Uses
How it works
General Information2
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CAS Number: 57-22-7
Molecular Formula: C46H56N4O10
Molecular Weight: 824.97
Melting Point: 218-220°C
Clear liquid
(taken by injection)
Synthesis from a Natural Source
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Vincristine has two natural sources:
Catharanthus roseus (Vinca rosea), the
Madagascar periwinkle, and
Tabernaemontana pachysiphon
This yield from the Madagascar periwinkle
is less than 1μg/g (.0003%)6
Synthesis from vinblastine
H2CrO4
Ethyl Acetate
2 hours, -83- -25°C
80-90% yield5
• This is the easiest and most common method of
synthesis, as well as one can give high yields
Synthetic Production
Discovered
in 2004
First route to make synthetic
vincristine6
Spectroscopy
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Mass Spectrum4: M+1=825
UV Spectrum1: 220, 255, 296 nm
IR Spectrum6: 3445, 2924, 2852, 1740,
1681, 1597, 1498, 1458, 1369, 1230,
1033, 747 cm-1
History and Uses
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Discovered in 1953 by Robert L. Noble,
and cleared by the FDA in 1963 as
Oncovin, marketed by Eli Lilly and Co.
Used to treat acute leukemias and all
lymphomas
Side effects include nervous system
damage and constipation
Work is being done to develop more
effective derivatives with fewer side
effects8
How it works
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Stops division of cells
Enters cell during mitosis and blocks
formation of microtubules of the mitotic
spindle during metaphase3,7
Bibliography
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(1) Anonymous Vincristine. In The Merck index: an encyclopedia of chemicals, drugs,
and biologicals; O'Neil, M. J., Ed.; Merck: Whitehouse Station, NJ, 2006; pp 17171718.
(2) Anonymous Chemfinder.com Database and Internet Searching.
http://chemfinder.cambridgesoft.com (accessed Jan. 22, 2007).
(3) Anonymous Overview: The Mitotic Spindle. http://www.sinauer.com/pdf/nspcellcycle-6-0.pdf (accessed Apr. 15, 2007).
(4) Choi, Y. H.; Kim, J.; Yoo, K. Supercritical Fluid Extraction and Liquid
Chromatography-Electrospray Mass Analysis of Vinblastine from Catharanthus
roseus. Chem. Pharm. Bull. 2002, 50, 1294--1296.
(5) Huhtikangas, A.; Laakso, I.; Seppaenen-Laakso, T.; Verma, A. Patent Application
Country: Application: FI; Patent Country: FI Patent 107924, 2001.
(6) Kuboyama, T.; Yokoshima, S.; Tokuyama, H.; Fukuyama, T. Stereocontrolled
total synthesis of (+)-vincristine. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 1196611970.
(7) Lurie, P. M.; Manaster, J.; Stryckmans, P. A.; Vamecq, G. Mode of Action of
Chemotherapy in vivo on Human Acute Leukemia--II. Vincristine. Europ. J. Cancer
1973, 9, 613--620.
(8) Szabo, L.; Bolcskei, H.; Eszter, B.; Mak, M.; Szantay, C. Synthesis of vinca
alkaloids and related compounds, Part XCV: Nitration study of vinblastine-type
bisindole alkaloids. Arch. Pharm. Pharm. Med. Chem. 2001, 334, 339--405.