Skip to main content

Essential Oils as Raw Materials in the Synthesis of Anticancer Drugs

  • Chapter
  • First Online:
Bioactive Essential Oils and Cancer

Abstract

Anticancer drugs are in high demand and are being encountered among natural products more frequently than in classical pharmaceutical innovations. Their synthesis has thus become relevant, and essential oils are potential raw materials for this endeavour. This chapter will present recent developments and a historical perspective on the synthesis of anticancer drugs from essential oil components.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aggarwal VK (2009) New uses for old building blocks. Nature Chem 1:433–434

    Article  CAS  Google Scholar 

  • Altmann K-H, Pfeiffer B, Arseniyadis S, Pratt BA, Nicolaou KC (2007) The chemistry and biology of epothilones—the wheel keeps turning. Chem Med Chem 2:396–423

    Article  CAS  PubMed  Google Scholar 

  • Andrews SP, Ball M, Wierschem F, Cleator E, Oliver S, Hogenauer K, Simic O, Antonello A, Hunger U, Smith MD, Ley SV (2007) Total synthesis of five thapsigargins: guaianolide natural products exhibiting sub-nanomolar SERCA inhibition. Chem Eur J 13:5688–5712

    Article  CAS  PubMed  Google Scholar 

  • Avery MA, Chong WKM, Jennings-Whites C (1992) Stereoselective total synthesis of (+)-artemisinin, the antimalarial constituent of Artemisia annua L. J Am Chem Soc 114:974–979

    Article  CAS  Google Scholar 

  • Breitmaier E (2006) Terpenes; flavors, fragrances, pharmaca, pheromones. Wiley-VCH, Weinheim

    Google Scholar 

  • Butler MS (2005) Natural products to drugs: natural product derived compounds in clinical trials. Nat Prod Rep 22:162–195

    Article  CAS  PubMed  Google Scholar 

  • Castoldi D, Caggiano L, Panigada L, Sharon O, Costa AM, Gennari C (2006) A formal total synthesis of eleutherobin using the ring-closing metathesis (RCM) reaction of a densely functionalized diene as the key step: investigation of the unusual kinetically controlled RCM stereochemistry. Chem Eur J 12:51–62

    Article  CAS  Google Scholar 

  • Chen X-T, Bhattacharya SK, Zhou B, Gutteridge CE, Pettus TRR, Danishefsky SJ (1999) The total synthesis of eleutherobin. J Am Chem Soc 121:6563–6579

    Article  CAS  Google Scholar 

  • Constantino MG, Beltrame M Jr, da Silva GVJ, Zukerman-Schpector J (1996) A novel asymmetric total synthesis of (+)-artemisinin. Synth Commun 26:321–329

    Article  CAS  Google Scholar 

  • Corey EJ, Czakó B, Kurti L (2007) Molecules and medicine. Wiley, Hoboken

    Google Scholar 

  • Cragg GM, Newman DJ, Snader KM (1997) Natural products in drug discovery and development. J Nat Prod 60:52–60

    Article  CAS  PubMed  Google Scholar 

  • Cragg GM, Grothaus PG, Newman DJ (2009) Impact of natural products on developing new anti-cancer agents. Chem Rev 109:3012–3043

    Article  CAS  PubMed  Google Scholar 

  • Croteau R, Kutchan TM, Lewis NG (2000) Natural products (secondary metabolites). In: Buchanan B, Gruissem W, Jones R (eds) Biochemistry & molecular biology of plants. American Society of Plant Physiologists, Rockville, pp 1250–1318

    Google Scholar 

  • Danishefsky SJ (2010) On the potential of natural products in the discovery of pharma leads: a case for reassessment. Nat Prod Rep 27:1114–1116

    Article  CAS  PubMed  Google Scholar 

  • Dewick PM (2009) Medicinal natural products; abiosynthetic approach, 3rd edn. Wiley, Baffins Lane

    Book  Google Scholar 

  • Dias DA, Urban S, Roessner U (2012) A historical overview of natural products in drug discovery. Metabolites 2:303–336

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ellis JM, Crimmins MT (2008) Strategies for the total synthesis of C2-C11 cyclized cembranoids. Chem Rev 108:5278–5298

    Article  CAS  PubMed  Google Scholar 

  • Erman WF (1985) Chemistry of the monoterpenes: an encyclopedic hand book, vol 1–2. Marcel Dekker, New York

    Google Scholar 

  • Esatbeyoglu T, Huebbe P, Ernst IM, Chin D, Wagner AE, Rimbach G (2012) Curcumin—from molecule to biological function. Angew Chem Int Ed Engl 51:5308–5332

    Article  CAS  PubMed  Google Scholar 

  • Feher M, Schmidt JM (2003) Property distributions: differences between drugs, natural products, and molecules from combinatorial chemistry. J Chem Inf Comput Sci 43:218–227

    Article  CAS  PubMed  Google Scholar 

  • Fellows IM, Kaelin DE Jr, Martin SF (2000) Application of ring-closing metathesis to the formal total synthesis of (+)-FR900482. J Am Chem Soc 122:10781–10787

    Article  CAS  Google Scholar 

  • Fürstner A, de Souza D, Turet L, Fenster MDB, Parra-Rapado L, Wirtz C, Mynott R, Lehmann CW (2007a) Total syntheses of the actin-binding macrolides latrunculin A, B, C, M, Sand 16-epi-Latrunculin B. Chem Eur J 13:115–134

    Article  PubMed  Google Scholar 

  • Fürstner A, Kirk D, Fenster MDB, Aissa C, de Souza D, Nevado C, Tuttle T, Thiel W, Muller O (2007b) Latrunculin analogues with improved biological profiles by “diverted total synthesis”: preparation, evaluation, and computational analysis. Chem Eur J 13:135–149

    Article  PubMed  Google Scholar 

  • Gao Y, Honzatko RB, Peters RJ (2012) Terpenoid synthase structures: a so far incomplete view of complex catalysis. Nat Prod Rep 29:1153–1175

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gennari C, Castoldi D, Sharon O (2007) Natural Products with taxol-like anti-tumor activity: synthetic approaches to eleutherobin and dictyostatin. Pure Appl Chem 79:173–180

    Article  CAS  Google Scholar 

  • Ghantous A, Gali-Muhtasib H, Vuorela H, Saliba NA, Darwiche N (2010) What made sesquiterpene lactones reach clinical trials. Drug Discov Today 15:668–678

    Article  CAS  PubMed  Google Scholar 

  • Gordaliza M (2007) Natural products as leads to anti-cancer drugs. Clin Transl Oncol 9:767–776

    Article  CAS  PubMed  Google Scholar 

  • Guenther E (ed) (1948–1952) Essential oils, vol 1–6. Van Nostrand, New York

    Google Scholar 

  • Jacoby M (2005) Taxol. Chem Eng News, 83(25)

    Google Scholar 

  • Johnson DS, Li JJ (2007) The art of drug synthesis. Wiley, Hoboken

    Book  Google Scholar 

  • Jørgensen L, McKerrall SJ, Kuttruff CA, Ungeheuer F, Felding J, Baran PS (2013) 14-step synthesis of (+)-ingenol from (+)-3-carene. Science 341:878–882

    Article  PubMed  Google Scholar 

  • Kupchan SM (1970) Recent advances in the chemistry of terpenoid tumor inhibitors. Pure Appl Chem 21:227–246

    CAS  PubMed  Google Scholar 

  • Lachance H, Wetzel S, Kumar K, Waldmann H (2012) Charting, navigating, and populating natural product chemical space for drug discovery. J Med Chem 55:5989–6001

    Article  CAS  PubMed  Google Scholar 

  • Lim HN, Parker KA (2013) Total synthesis of kingianin A. Org Lett 15:398–401

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liu H-J, Yeh W-L, Chew SY (1993) A total synthesis of the antimarial natural product (+)-qinghaosu. Tetrahedron Lett 34:4435–4438

    Article  CAS  Google Scholar 

  • Liu Y-Q, Yang L, Tian X (2007) Podophyllotoxin: current perspectives. Curr Bioact Compd 3:37–66

    Article  CAS  Google Scholar 

  • Maffei ME, Gertsch J, Appendino G (2011) Plant volatiles: production, function and pharmacology. Nat Prod Rep 28:1359–1380

    Article  CAS  PubMed  Google Scholar 

  • Magauer T, Martin HJ, Mulzer J (2010) Ring-closing metathesis and photo-fries reaction for the construction of the ansamycin antibiotic kendomycin: development of a protecting group free oxidative endgame. Chem Eur J 16:507–519

    Article  CAS  PubMed  Google Scholar 

  • Magedov IV, Manpadi M, Van slambrouck S, Steelant WFA, Rozhkova E, Przheval’skii NM, Rogelj S, Kornienko A (2007) Discovery and investigation of antiproliferative and apoptosis-inducing properties of new heterocyclic podophyllotoxin analogues accessible by a one-step multicomponent synthesis. J Med Chem 50:5183–5192

    Article  CAS  PubMed  Google Scholar 

  • Maimone TJ, Baran PS (2007) Modern synthetic efforts toward biologically active terpenes. Nat Chem Biol 3:396–407

    Article  CAS  PubMed  Google Scholar 

  • Mandel AL, Bellosta V, Curran DP, Cossy J (2009) A versatile route to the tulearin class of macrolactones: synthesis of a stereoisomer of Tulearin A. Org Lett 11:3282–3285

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Martin HJ, Pojarliev P, Kählig H, Mulzer J (2001) The 12,13-diol cyclization approach for a truly sereocontrolled total synthesis of epothilone b and the synthesis of a conformationally restrained analogue. Chem Eur J 7:2261–2271

    Article  CAS  PubMed  Google Scholar 

  • Mishra BB, Tiwari VK (2011) Natural products in drug discovery: clinical evaluations and investigations. In: Tiwari VK, Mishra BB (eds) Natural products in drug discovery: clinical evaluations and investigations, in opportunity, challenge and scope of natural products in medicinal chemistry. Research Signpost, Kerala, pp 1–62

    Google Scholar 

  • Mondal S, Bandyopadhyay S, Ghosh MK, Mukhopadhyay S, Roy S, Mandal C (2012) Natural products: promising resources for cancer drug discovery. Anti-Cancer Agents Med Chem 12:49–75

    Article  CAS  Google Scholar 

  • Montaser R, Luesch H (2011) Marine natural products: a new wave of drugs? Future Med Chem 3:1475–1489

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mulzer J, Martin HJ (2004) Lessons learned from macrolide synthesis. Chem Rec 3:258–270

    Article  CAS  PubMed  Google Scholar 

  • Nagar N, Jat RK, Saharan R, Verma S, Sharma D, Bansal K (2011) Podophyllotoxin and their glycosidic derivatives. Pharmacophore 2:124–134

    CAS  Google Scholar 

  • Neidle S, Buss AD, Butler MS (eds) (2010) Natural product chemistry for drug discovery. Royal Society of Chemistry, Milton Road

    Google Scholar 

  • Newman DJ, Cragg GM, Snader KM (2003) Natural products as sources of new drugs over the period 1981–2002. J Nat Prod 66:1022–1037

    Article  CAS  PubMed  Google Scholar 

  • Newman DJ (2008) Natural products as leads to potential drugs: an old process or the new hope for drug discovery? J Med Chem 51:2589–2599

    Article  CAS  PubMed  Google Scholar 

  • Newman DJ, Cragg DM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75:311–335

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nicolaou KC, Montagnon T (2008) Molecules that changed the world. Wiley-VCH, Weinheim

    Google Scholar 

  • Nicolaou KC, Dai W-M, Guy RK (1994) Chemistry and biology of taxol. Angew Chem Int Ed Engl 33:15–44

    Article  Google Scholar 

  • Nicolaou KC, Xu J-Y, Kim S, Pfefferkorn J, Ohshima T, Vourloumis D, Hosokawa S (1998) Total synthesis of Sarcodyctins A and B. J Am Chem Soc 120:8661–8673

    Article  CAS  Google Scholar 

  • Nicolaou KC, Chen JS, Dalby SM (2009) From nature to the laboratory and into the clinic. Bioorg Med Chem 17:2290–2303

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nishikawa Y, Kitajima M, Takayama H (2008) First asymmetric total syntheses of cernuane-type Lycopodium Alkaloids, Cernuine, and Cermizine D. Org Lett 10:1987–1990

    Article  CAS  PubMed  Google Scholar 

  • Ojima I, Chakravarty S, Inoue T, Lin S, He L, Horwitz SB, Kuduk SD, Danishefsky SJ (1999) A common pharmacophore for cytotoxic natural products that stabilize microtubules. Proc Natl Acad Sci U S A 96:4256–4261

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Paterson I, Anderson EA (2005) The renaissance of natural products as drug candidates. Science 310:451–453

    Article  PubMed  Google Scholar 

  • Pedersen U, Rasmussen PB, Lawesson S-O (1985) Synthesis of naturally occurring curcuminoids and related compounds. Liebigs Ann Chem 1557–1569

    Google Scholar 

  • Sawadogo WR, Schumacher M, Teiten MH, Cerella C, Dicato M, Diederich M (2013) A survey of marine natural compounds and their derivatives with anti-cancer activity reported in 2011. Molecules 18:3641–3673

    Article  CAS  PubMed  Google Scholar 

  • Sell CS (2003) A fragrant introduction to terpenoid chemistry. RSC Publishing, Cambridge

    Google Scholar 

  • Shing TKM, Lee CM, Lo HY (2004) A synthetic approach toward taxol analogs: studies on the construction of the CD ring. Tetrahedron 60:9179–9197

    Article  CAS  Google Scholar 

  • Simmons TL, Andrianasolo E, McPhail K, Flatt P, Gerwick WH (2005) Marine natural products as anti-cancer drugs. Mol Cancer Ther 4:333–342

    CAS  PubMed  Google Scholar 

  • Srikrishna A, Kumar PP, Reddy TJ (2005) Enantiospecific synthesis of B-Seco-Nortaxanes from two molecules of carvone. Indian J Chem 44B:1430–1436

    CAS  Google Scholar 

  • Tietze LF, Bell HP, Chandrasekhar S (2003) Natural product hybrids as new leads for drug discovery. Angew Chem Int Ed 42:3996–4028

    Article  CAS  Google Scholar 

  • Wender PA, Badham NF, Conway SP, Floreancig PE, Glass TE, Houze JB, Krauss NE, Lee D, Marquess DG, McGrane PL, Meng W, Natchus MG, Shuker AJ, Sutton JC, Taylor RE (1997) The pinene path to Taxanes. 6. A concise stereocontrolled synthesis of taxol. J Am Chem Soc 119:2757–2758

    Article  CAS  Google Scholar 

  • Wessjohann L, Scheid GO, Eichelberger U, Umbreen S (2013) Total synthesis of Epothilone D: the Nerol/Macroaldolization approach. J Org Chem 78:10588–10595

    Article  CAS  PubMed  Google Scholar 

  • Willot M, Radtke L, Konning D, Frohlich R, Gessner VH, Strohmann C, Christmann M (2009) Total synthesis and absolute configuration of the guaiane sesquiterpene englerin A. Angew Chem Int Ed 48:9105–9108

    Article  CAS  Google Scholar 

  • Wilson RM, Danishefsky SJ (2007) Applications of total synthesis toward the discovery of clinically useful anti-cancer agents. Chem Soc Rev 36:1207–1226

    Article  CAS  PubMed  Google Scholar 

  • Yin J, Kong L, Wang C, Shi Y, Cai S, Gao S (2013) Biomimetic synthesis of equisetin and (+)-fusarisetin A. Chem Eur J 19:13040–13046

    Article  CAS  PubMed  Google Scholar 

  • Yusufi M, Banerjee S, Mohammad M, Khatal S, Swamy KV, Khan EM, Aboukameel A, Sarkar FH, Padhye S (2013) Synthesis, characterization and anti-tumor activity of novel thymoquinone analogs against pancreatic cancer. Bioorg Med Chem Lett 23:3101–3104

    Article  CAS  PubMed  Google Scholar 

  • Zahel M, Keßberg A, Metz P (2013) A short enantioselective total synthesis of (−)-englerin A. Angew Chem Int Ed 52:5390–5392

    Article  CAS  Google Scholar 

  • Zhai J-D, Li D, Long J, Zhang H-L, Lin J-P, Qiu C-J, Zhang Q, Chen Y (2012) Biomimetic semisynthesis of arglabin from parthenolide. J Org Chem 77:7103–7107

    Article  CAS  PubMed  Google Scholar 

  • Zhang Q, Lu Y, Ding Y, Zhai J, Ji Q, Ma W, Yang M, Fan H, Long J, Tong Z, Shi Y, Jia Y, Han B, Zhang W, Qiu C, Ma X, Li Q, Shi Q, Zhang H, Li D, Zhang J, Lin J, Li LY, Gao Y, Chen Y (2012) Guaianolide sesquiterpene lactones, a source to discover agents that selectively inhibit acute myelogenous leukemia stem and progenitor cells. J Med Chem 55:8757–8769

    Article  CAS  PubMed  Google Scholar 

  • Zhou Q, Chen X, Ma D (2010) Asymmetric, protecting-group-free total synthesis of (−)-englerin A. Angew Chem Int Ed 49:3513–3516

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors wish to thank the following Brazilian agencies for financial support and fellowships; FAPESP (2011/13993-2; 2013/02311-3; 2013/06532-4), CAPES and CNPq. The authors thank all former and present collaborators, for their studied input and hard work on our projects. They also acknowledge the donation of monoterpenes by Firmenich SA.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Timothy J. Brocksom .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Brocksom, T., de Oliveira, K., Ferreira, M., Servilha, B. (2015). Essential Oils as Raw Materials in the Synthesis of Anticancer Drugs. In: de Sousa, D. (eds) Bioactive Essential Oils and Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-19144-7_4

Download citation

Publish with us

Policies and ethics