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Chemical structure of the vinca alkaloid
vincristine
Vinca alkaloids are a set of
anti-mitotic and
anti-microtubule
alkaloid agents originally derived from the periwinkle plant
Catharanthus roseus (
basionym Vinca rosea ) and other
vinca plants. They block
beta-tubulin polymerization in a dividing cell.
Sources
The Madagascan periwinkle
Catharanthus roseus L. is the source for a number of important natural products,
[1] including
catharanthine and
vindoline
[2] and the vinca alkaloids it produces from them:
leurosine and the
chemotherapy agents
vinblastine
[3] and
vincristine ,
[4] all of which can be obtained from the plant.
[5]
[6]
[7]
[8] The newer
semi-synthetic chemotherapeutic agent
vinorelbine is used in the treatment of
non-small-cell lung cancer
[7]
[9] and is not known to occur naturally. However, it can be prepared either from vindoline and catharanthine
[7]
[10] or from leurosine,
[11] in both cases by synthesis of anhydrovinblastine, which "can be considered as the key intermediate for the synthesis of vinorelbine."
[7] The leurosine pathway uses the
Nugent–RajanBabu reagent in a highly
chemoselective de-oxygenation of leurosine.
[12]
[11] Anhydrovinblastine is then reacted sequentially with
N -bromosuccinimide and
trifluoroacetic acid followed by
silver tetrafluoroborate to yield vinorelbine.
[10]
Applications
Vinca alkaloids are used in
chemotherapy for cancer. They are a class of
cell cycle –specific
cytotoxic drugs that work by inhibiting the ability of cancer cells to divide: Acting upon tubulin, they prevent it from forming into
microtubules , a necessary component for
cellular division .
[13] The vinca alkaloids thus prevent microtubule polymerization , as opposed to the mechanism of action of
taxanes .
Vinca alkaloids are now produced
synthetically and used as drugs in cancer therapy and as immunosuppressive drugs. These compounds include vinblastine, vincristine,
vindesine , and vinorelbine. Additional researched vinca alkaloids include
vincaminol ,
vineridine , and
vinburnine .
Vinpocetine is a semi-synthetic
derivative of
vincamine (sometimes described as "a
synthetic
ethyl ester of apovincamine").
[14]
Minor vinca alkaloids include minovincine, methoxyminovincine, minovincinine, vincadifformine, desoxyvincaminol, and vincamajine.
[15]
[16]
[17]
References
^ van der Heijden, Robert; Jacobs, Denise I.; Snoeijer, Wim; Hallard, Didier; Verpoorte, Robert (2004). "The Catharanthus alkaloids: Pharmacognosy and biotechnology".
Current Medicinal Chemistry . 11 (5): 607–628.
doi :
10.2174/0929867043455846 .
PMID
15032608 .
^ Hirata, K.; Miyamoto, K.; Miura, Y. (1994).
"Catharanthus roseus L. (Periwinkle): Production of Vindoline and Catharanthine in Multiple Shoot Cultures" . In Bajaj, Y. P. S. (ed.).
Biotechnology in Agriculture and Forestry 26 . Medicinal and Aromatic Plants. Vol. VI.
Springer-Verlag . pp.
46–55 .
ISBN
9783540563914 .
^ Sears, Justin E.;
Boger, Dale L. (2015).
"Total Synthesis of Vinblastine, Related Natural Products, and Key Analogues and Development of Inspired Methodology Suitable for the Systematic Study of Their Structure-Function Properties" .
Accounts of Chemical Research . 48 (3): 653–662.
doi :
10.1021/ar500400w .
PMC
4363169 .
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^ Kuboyama, Takeshi; Yokoshima, Satoshi; Tokuyama, Hidetoshi; Fukuyama, Tohru (2004).
"Stereocontrolled total synthesis of (+)-vincristine" .
Proceedings of the National Academy of Sciences of the United States of America . 101 (33): 11966–11970.
Bibcode :
2004PNAS..10111966K .
doi :
10.1073/pnas.0401323101 .
PMC
514417 .
PMID
15141084 .
^ Gansäuer, Andreas; Justicia, José; Fan, Chun-An; Worgull, Dennis; Piestert, Frederik (2007).
"Reductive C—C bond formation after epoxide opening via electron transfer" . In
Krische, Michael J. (ed.). Metal Catalyzed Reductive C—C Bond Formation: A Departure from Preformed Organometallic Reagents . Topics in Current Chemistry. Vol. 279.
Springer Science & Business Media . pp. 25–52.
doi :
10.1007/128_2007_130 .
ISBN
9783540728795 .
^ Cooper, Raymond; Deakin, Jeffrey John (2016).
"Africa's gift to the world" . Botanical Miracles: Chemistry of Plants That Changed the World .
CRC Press . pp. 46–51.
ISBN
9781498704304 .
^
a
b
c
d Keglevich, Péter; Hazai, Laszlo; Kalaus, György; Szántay, Csaba (2012).
"Modifications on the basic skeletons of vinblastine and vincristine" .
Molecules . 17 (5): 5893–5914.
doi :
10.3390/molecules17055893 .
PMC
6268133 .
PMID
22609781 .
^ Raviña, Enrique (2011).
"Vinca alkaloids" . The evolution of drug discovery: From traditional medicines to modern drugs .
John Wiley & Sons . pp. 157–159.
ISBN
9783527326693 .
^ Faller, Bryan A.; Pandi, Trailokya N. (2011).
"Safety and efficacy of vinorelbine in the treatment of non-small cell lung cancer" .
Clinical Medicine Insights: Oncology . 5 : 131–144.
doi :
10.4137/CMO.S5074 .
PMC
3117629 .
PMID
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^
a
b Ngo, Quoc Anh; Roussi, Fanny; Cormier, Anthony; Thoret, Sylviane; Knossow, Marcel; Guénard, Daniel; Guéritte, Françoise (2009). "Synthesis and biological evaluation of Vinca alkaloids and phomopsin hybrids".
Journal of Medicinal Chemistry . 52 (1): 134–142.
doi :
10.1021/jm801064y .
PMID
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^
a
b Hardouin, Christophe; Doris, Eric; Rousseau, Bernard; Mioskowski, Charles (2002). "Concise synthesis of anhydrovinblastine from leurosine".
Organic Letters . 4 (7): 1151–1153.
doi :
10.1021/ol025560c .
PMID
11922805 .
^ Morcillo, Sara P.; Miguel, Delia; Campaña, Araceli G.; Cienfuegos, Luis Álvarez de; Justicia, José; Cuerva, Juan M. (2014).
"Recent applications of Cp2 TiCl in natural product synthesis" .
Organic Chemistry Frontiers . 1 (1): 15–33.
doi :
10.1039/c3qo00024a .
hdl :
10481/47295 .
^ Takimoto, C. H.; Calvo, E. (2008).
"Chapter 3: Principles of Oncologic Pharmacotherapy" . In Pazdur, R.; Wagman, L. D.; Camphausen, K. A.; Hoskins, W. J. (eds.). Cancer Management: A Multidisciplinary Approach (11th ed.).
ISBN
978-1-891483-62-2 . Archived from
the original on 2009-05-15. Retrieved 2011-05-26 .
^ Lörincz C, Szász K, Kisfaludy L (1976). "The synthesis of ethyl apovincaminate". Arzneimittel-Forschung . 26 (10a): 1907.
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^ Plat, M; Fellion, E; Le Men, J; Janot, M (1962). "4 new alkaloids of Vinca minor L.: minovincine, methoxyminovincine, minovincinine and (-) vincadifformine, alkaloids of periwinkles". Ann. Pharm. Fr. (in French). 20 : 899–906.
PMID
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^ Smeyers, Yves G.; Smeyers, Nadine J.; Randez, Juan J.; Hernandez-Laguna, A.; Galvez-Ruano, E. (1991). "A structural and pharmacological study of alkaloids of Vinca Minor ". Molecular Engineering . 1 (2): 153–160.
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S2CID
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^ Janot, M. M.; Le Men, J; Fan, C (1958). "The alkaloids of the periwinkles (Vinca ): Relation between, vincamedine and vincamajine". Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences . 247 (25): 2375–7.
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