Synthetic Strategies toward the Guaiane Sesquiterpene Englerin A

Abstract

Englerin A is a guaiane sesquiterpene with potent and selective growth inhibition activity against six human renal cancer cell lines. Since the disclosure of its structure in 2009, englerin A has been the subject of intense study by the synthetic organic chemistry community, and several elegant strategies have been developed for the total synthesis of this exciting natural product. These strategies are discussed herein.

Key words

terpenoids - total synthesis - antitumor agents - natural products - carbonyl

References

• 1a Ratnayake R. Covell D. Ransom TT. Gustafson KR. Beutler JA. Org. Lett.  2009,  11:  57 
• 1b Beutler JA, Ratnayake R, Covell D, and Johnson TR. inventors; WO  2009/088854. 
• 2a Knauseder F. Brandl E. J. Antibiot.  1976,  29:  125 
• 2b Saito N. Kameyama N. Kubo A. Tetrahedron  2000,  56:  9937 
• 2c Costantino V. Dell’Aversano C. Fattorusso E. Mangoni A. Steroids  2000,  65:  138 
• 3a Carney EW. Freshour NL. Dittenber DA. Dryzga MD. Toxicol. Sci.  1999,  50:  117 
• 3b Bove KE. Am. J. Clin. Pathol.  1966,  45:  46 
• 4 Willot M. Radtke L. Könning D. Fröhlich R. Gessner VH. Strohmann C. Christmann M. Angew. Chem. Int. Ed.  2009,  48:  9105 
• 5 For a similar bond formation in the context of the englerins, see: Ushakov DB. Navickas V. Ströbele M. Maichle-Mössmer C. Sasse F. Maier ME. Org. Lett.  2011,  13:  2090 
• 6 Radtke L. Willot M. Sun H. Ziegler S. Sauerland S. Strohmann C. Fröhlich R. Habenberger P. Waldmann H. Christmann M. Angew. Chem. Int. Ed.  2011,  50:  3998 
• 7 Nicolaou KC. Kang Q. Ng SY. Chen DY.-K. J. Am. Chem. Soc.  2010,  132:  8219 
• 8 Xu J. Caro-Diaz EJE. Theodorakis EA. Org. Lett.  2010,  12:  3708 
• For a recent review of [5+2] cycloaddition chemistry, see:
• 9a Pellissier H. Adv. Synth. Catal.  2011,  353:  189 
• For a related cycloaddition strategy in the context of guaiane sesquiterpenes, see:
• 9b Navickas V. Ushakov DB. Maier ME. Ströbele M. Meyer H.-J. Org. Lett.  2010,  12:  3418 
• 10 Davies HML. Ahmed G. Churchill MR. J. Am. Chem. Soc.  1996,  118:  10774 
• 11 For a related organocatalytic [4+3] cycloaddition in the context of the englerins, see: Sun B.-F. Wang C.-L. Ding R. Xu J.-Y. Lin G.-Q. Tetrahedron Lett.  2010,  52:  2155 
• 12 Zhou Q. Chen X. Ma D. Angew. Chem. Int. Ed.  2010,  49:  3513 
• 13 Molawi K. Delpont N. Echavarren AM. Angew. Chem. Int. Ed.  2010,  49:  3517 
• 14 Willot M. Christmann M. Nat. Chem.  2011,  2:  519 
• 15 Jiménez-Núñez E. Molawi K. Echavarren AM. Chem. Commun.  2009,  7327 
• 16a Li Z. Nakashige M. Chain WJ. J. Am. Chem. Soc.  2011,  133:  6553 
• 16b See also: Szostak M. Procter DJ. Angew. Chem. Int. Ed.  2011,  50:  7737 
• 17a Nicolaou KC. Ellery SP. Chen JS. Angew. Chem. Int. Ed.  2009,  48:  7140 
• 17b Procter DJ. Flowers RA. Skrydstrup T. Organic Synthesis Using Samarium Diiodide: A Practical Guide   RSC Publishing; Cambridge: 2009. 
• 18 Chan KP. Chen DY.-K. ChemMedChem  2011,  6:  420