A New and Efficient Strategy for the Synthesis of Podophyllotoxin and Its Analogues

Abstract

[structure: see text]. An efficient and stereoselective strategy for the total synthesis of podophyllotoxin was developed. This route leads to podophyllotoxin 1 in only 12 steps with 29% overall yield. A notable feature of this synthetic strategy is the use of the cascade addition-alkylation to ensure the key C1-C2 stereochemistry that is pivotal for the synthesis of podophyllotoxin.

A Review on Hemisynthesis, Biosynthesis, Biological Activities, Mode of Action, and Structure-Activity Relationship of Podophyllotoxins: 2003- 2007

“…However, the availability of material from the most productive species is becoming increasingly limited and insufficient because of intense collection from the wild, slow plant growth, poor reproduction, and delays in developing crop cultivation methods. Although total chemical synthesis of PPT and its analogs/derivatives has been accomplished [75][76][77][78][79][80][81][82][83][84], it is not an option from a commercial point of view because of the four chiral positions, complex reaction steps required and low product yields [85]. Therefore, alternatively to the isolation from natural sources and to the total chemical synthesis, plant cell suspension cultures are considered to be useful in producing sufficient amounts of scientifically and commercially valuable compounds.…”

Investigation and Expression of the Secoisolariciresinol Dehydrogenase Gene Involved in Podophyllotoxin Biosynthesis

“…One of these sources is the rhizomes of the plant Podophyllum peltatum [6]. Due to a combination of the slow growth-rate of the plant and increasing demand for PPT [7][8][9], various other approaches for the chemical synthesis and in vitro production of PPT have been explored [1,[10][11][12][13][14]. These methods have so far proven to be inadequate for the commercial production of PPT due to low yields and high costs.…”

Selection methodology with scoring system: Application to Mexican plants producing podophyllotoxin related lignans

“…Other derivatives are being developed for the treatment of cancer (You, 2005) as well as rheumatoid arthritis (Svensson and Pettersson, 2003). Wu et al (2007) described a process for chemically synthesizing 2-7 cyclolignans, however it is costly and therefore not economically viable. Instead, the extraction from the subterrestrial parts of wild Podophyllum hexandrum is preferred, but this has led to permanent overexploitation of a slowgrowing plant, which is now becoming an endangered species in India.…”