Total synthesis of (-)-podophyllotoxin

This page is for the project done by Eric Stefanowicz and Matt McCabe.

Introduction

Podophyllotoxin is the main active constituent in Podophyllum peltatum, also known as the American Mandrake (mayapple plant)(1). Podophyllotoxin is an extract from the plant rhizome(2). It is obtained via buffer extraction of the glucopyranoside, then converted from podophyllotoxin 4-O-β-D-glucopyranoside into the aglycone(3). It is known for its homeopathic remedies, which is a dilute form of an active ingredient (Often 0.5% solutions). Do not confuse it with a herbal remedy, which is a highly pure form of an active ingredient(1). It is a lignan which is a class of phytoestrogen (estrogen like structure)(4). An etoposide of podophyllotoxin is a candidate for attacking cancers, treating rheumatoid arthritis, psoriasis and malaria.

Natural Occurrence

Podophyllum Peltatum occurs naturally in the Adirondacks (green regions of map)(5). It is found in moist soils in rich woods, pastures etc. The seeds ripen July-August, and the fruits are edible, however, unripened fruit act as a strong laxative, and too much of the fruit causes colic(1).

References

1. Plants for a Future (2008). Podophyllum Peltatum. Plants for a Future: Edible, Medicinal, and Useful Plants for a Healthier World Retrieved 30 March 2010 from http://www.pfaf.org/database/plants.php?Podophyllum+peltatum

2. “Podophyllotoxin”. Wikipedia, The Free Encyclopedia. 28 February 2010, 23:54. Wikimedia Foundation, Inc. Retrieved 30 March, 2010 from http://en.wikipedia.org/wiki/Podophyllotoxin

3. Moraes, R.M., H. Lata, E. Bedir, M. Maqbool, and K. Cushman. 2002. The American mayapple and its potential for podophyllotoxin production. p. 527–532. In: J. Janick and A. Whipkey (eds.), Trends in new crops and new uses. ASHS Press, Alexandria, VA. Retrieved 31 March, 2010 from http://www.hort.purdue.edu/newcrop/ncnu02/v5-527.html

4. “Lignan”. Wikipedia, The Free Encyclopedia. 3 March, 2010, 14:09. Wikimedia Foundation, Inc. Retrieved 1 April, 2010 from http://en.wikipedia.org/wiki/Lignin

5. USDA. (2010). County Distribution of Podophyllum Peltatum – L. Mayapple POPE. Retrieved 31 March, 2010 from http://plants.usda.gov/java/county?state_name=NewYork&statefips=36&symbol=POPE

6. Yadav, J.S. Reddy, B.V.S. Basak, A.K. Narsaiah, A.V. (2004). Recyclable 2nd Generation Ionic Liquids as Green Solvents for the Oxidation of Alcohols with Hypervalent Iodine Reagents. Tetrahedron, 60, 2131-2135.

7. D. F. Taber. (6 September, 2004). Synthesis of (-)-Podophyllotoxin. Org. Chem. Highlights. Retrieved 24 March, 2010 from� http://www.organic-chemistry.org/Highlights/2004/06September.shtm

8. Reynolds, A.J. Scott, A.J. Turner, C.I. Sherburn, M.S. (2003). The Intramolecular Carboxyarylation Approach to Podophyllotoxin. JACS, 125, 12108-12109.

9. Gordaliza, M. (1 December, 2006). Podophyllotoxin: Sources, Extraction, and Preparation of Cytotoxic Analog Compounds. Retrieved 31 March, 2010 from http://old.iupac.org/publications/cd/medicinal_chemistry/Practica-VI-1.pdf

10. Li-She Gan, Zhen-Zhen Wang, and Chang-Xin Zhou. (2009). Solubility of Podophyllotoxin in Six Organic Solvents From (283.2 to 323.2). J. Chem. Eng. Data, 54, 160–161. Retrieved 31 March, 2010 from http://pubs.acs.org/doi/pdf/10.1021/je8007028

11. Wu, Y. Zhang, H. Zhao, Y. Zhao, J. Chen, J. Li, L. (2007). A New and Efficient Strategy for the Synthesis of Podophyllotoxin and Its Analogues. Organic Letters, 9, 1199-1202. Retrieved 31 March, 2010 from http://webproxy.potsdam.edu:2186/doi/pdf/10.1021/ol0630954

12. Wu, Y. Zhao, J. Chen, J. Pan, C. Li, L. Zhang, H. (2009). Enantioselective Sequential Conjugate Addition-Allylation Reactions: A Concise Total Synthesis of (+)-Podophyllotoxin. Organic Letters, 11, 597-600. Retrieved 31 March, 2010 from http://webproxy.potsdam.edu:2186/doi/pdf/10.1021/ol8026208

13. Ngan V. (2009). Podophyllotoxin. DermNet NZ. Retrieved 30 March, 2010 from http://www.dermnet.org.nz/treatments/podophyllotoxin.html

14. Canel, C. Moraes, R.M. Dayan, F.E. Ferreira, D. (2000). Podophyllotoxin. Phytochemistry, 54, 115-120.