Asymmetric total synthesis of (–)-podophyllotoxin

Bush, Edward J.; Jones, David W.

doi:10.1039/p19960000151

Cited by 45 publications

(18 citation statements)

References 15 publications

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“…Due to ever increasing demand for podophyllotoxin, long juvenile phase and poor fruit setting ability of P. hexandrum, overexploitation, and lack of organized cultivations have made the plant "critically endangered" (Majumder and Jha 2009). However, new routes for total synthesis of podophyllotoxin have been discovered (Bush and Jones 1995;Berkowitz et al 2000). But these are not economically feasible due to low yield.…”

Section: Fusarium Oxysporummentioning

confidence: 99%

Endophytic fungi: novel sources of anticancer lead molecules

Chandra

2012

Appl Microbiol Biotechnol

225

120

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Cancer is a major killer disease all over the world and more than six million new cases are reported every year. Nature is an attractive source of new therapeutic compounds, as a tremendous chemical diversity is found in millions of species of plants, animals, and microorganisms. Plant-derived compounds have played an important role in the development of several clinically useful anti-cancer agents. These include vinblastine, vincristine, camptothecin, podophyllotoxin, and taxol. Production of a plant-based natural drug is always not up to the desired level. It is produced at a specific developmental stage or under specific environmental condition, stress, or nutrient availability; the plants may be very slow growing taking several years to attain a suitable growth phase for product accumulation and extraction. Considering the limitations associated with the productivity and vulnerability of plant species as sources of novel metabolites, microorganisms serve as the ultimate, readily renewable, and inexhaustible source of novel structures bearing pharmaceutical potential. Endophytes, the microorganisms that reside in the tissues of living plants, are relatively unstudied and offer potential sources of novel natural products for exploitation in medicine, agriculture and the pharmaceutical industry. They develop special mechanisms to penetrate inside the host tissue, residing in mutualistic association and their biotransformation abilities opens a new platform for synthesis of novel secondary metabolites. They produce metabolites to compete with the epiphytes and also with the plant pathogens to maintain a critical balance between fungal virulence and plant defense. It is therefore necessary that the relationship between the plants and endophytes during the accumulation of these secondary metabolites is studied. Insights from such research would provide alternative methods of natural product drug discovery which could be reliable, economical, and environmentally safe.

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Section: Fusarium Oxysporummentioning

confidence: 99%

Endophytic fungi: novel sources of anticancer lead molecules

Chandra

2012

Appl Microbiol Biotechnol

225

120

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“…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.…”

Section: Biosynthesismentioning

confidence: 98%

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

徐¹,

Lv²,

Tian³

2009

CMC

187

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Podophyllotoxin is an important and much sought after antimitotic natural lead compound, since it paved the way for three hemisynthetic derivatives of podophyllotoxin, e.g., etoposide, teniposide and etopophos, which are widely used as anticancer drugs and show good clinical effects against several types of neoplasms. Although the publication of the recent reviews by Gordaliza in 2004 and You in 2005, which covered the literatures concerning podophyllotoxin until the early part of 2003, there have been significant number of works carried out on podophyllotoxin recently. Therefore, this review presents up-to-date coverage of podophyllotoxin in regard to hemisynthesis, biosynthesis, biological activities, mode of action and structure-activity relationship.

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“…Subsequent C4 oxidative decarboxylation, hydrolysis of the chiral auxiliary, reduction and lactonisation afforded (-)-podophyllotoxin (5) in 15 % overall yield from pyrone 94 (Scheme 19). [59] Whilst the Diels-Alder reaction is most commonly undertaken to realise a 1,2 3,4 disconnection strategy, Klemm and Yamaguchi have reported an alternative 2,3 1,6 bond construction strategy involving the intramolecular DielsAlder reaction of propargylic ester 98. Whilst catalytic reduction of the lactone 61 afforded the all-cis isomer, use of the free hydroxy acid 99 led to the desired 1,2-cis,2,3-trans stereochemistry, albeit in low yield (Scheme 20).…”

Section: C-ring Formation By Cycloaddition Reactionsmentioning

confidence: 99%

Advances in the Synthesis of Aryltetralin Lignan Lactones

Sellars

Steel

2007

Eur J Org Chem

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Etoposide and tenoposide, derivatives of the aryltetralin lignan lactone podophyllotoxin (5), are clinically important anticancer agents. The structure of podophyllotoxin includes four contiguous chiral centres contained within a stereochemically unstable trans‐fused tetrahydronaphthalene lactone skeleton. Reflecting this challenging structure and important biological role there has been long‐standing interest in developing efficient stereocontrolled syntheses of this class of natural product. This microreview summarises the key developments towards this end focussing on more recent developments both from within the authors group and elsewhere.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

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Asymmetric total synthesis of (–)-podophyllotoxin

Cited by 45 publications

References 15 publications

Endophytic fungi: novel sources of anticancer lead molecules

Endophytic fungi: novel sources of anticancer lead molecules

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

Advances in the Synthesis of Aryltetralin Lignan Lactones

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