Synlett 2007(10): 1477-1489  
DOI: 10.1055/s-2007-980382
ACCOUNT
© Georg Thieme Verlag Stuttgart · New York

Strategies to Bypass the Taxol Problem. Enantioselective Cascade Catalysis, a New Approach for the Efficient Construction of Molecular Complexity

Abbas M. Walji, David W. C. MacMillan*
Merck Center for Catalysis at Princeton University, Washington Rd, Princeton, NJ 08544, USA
e-Mail: [email protected];
Further Information

Publication History

Received 19 April 2007
Publication Date:
06 June 2007 (online)

Abstract

Millions of years of evolution have allowed Nature to ­develop ingenious synthetic strategies and reaction pathways for the construction of architectural complexity. In contrast, the field of chemical synthesis is young with its beginnings dating back to the early 1800’s. Remarkably, however, the field of chemical synthesis appears capable of building almost any known natural isolate in small quantities, yet we appear to be many years away from operational strategies or technologies that will allow access to complexity on a scale suitable for society’s consumption. This essay attempts to define some of the issues that currently hamper our ability to efficiently produce complex molecules via large-scale total synthesis. In particular, issues such as ‘regime of scale’ and ‘stop-and-go synthesis’ are discussed in terms of a specific example (the taxol problem) and more broadly as they apply to the large-scale production of complex targets. As part of this essay we discuss the use of enantioselective cascade catalysis as a modern conceptual strategy to bypass many of the underlying features that generally prevent total synthesis being utilized on a manufacturing scale. Last we provide a brief review of the state of the art with respect to complex ­molecule production via enantioselective cascade catalysis.

1 Introduction

1.1 Taxol

1.2 Benefits and Therapy

1.3 Commercialization Problems and Ultimate Production Route

1.4 Chemical Synthesis of Taxol

1.5 Regime of Scale

1.6 The Problem of ‘Stop-and-Go’ Synthesis

1.7 Nature’s Approach to the Synthesis of Complexity

2 Cascade Catalysis as a Key Strategy for Laboratory ­Complex Target Synthesis

2.1 Iterative Cascade Catalysis

2.2 Cascade Catalysis Based on Multiple Reaction Types

2.3 Cycle-Specific Cascade Catalysis

3 Summary

    References and Notes

  • 1a Woodward RB. Pure Appl. Chem.  1973,  33:  145 
  • 1b Eschenmoser A. Wintner CE. Science  1977,  196:  1410 
  • 2 Corey EJ. Kang M.-C. Desai MC. Ghosh AK. Houpis IN. J. Am. Chem. Soc.  1988,  110:  649 
  • 3 Armstrong RW. Beau JM. Cheon SH. Christ WJ. Fujioka H. Ham W.-H. Hawkins LD. Jin H. Kang SH. Kishi Y. Martinelli MJ. McWhorter WW. Mizuno M. Nakata M. Stutz AE. Talamas FX. Taniguchi M. Tino JA. Ueda K. Uenishi J. White JB. Yonaga M. J. Am. Chem. Soc.  1989,  111:  7530 ; and references cited therein
  • 4a Holton RA. Somoza C. Kim HB. Liang F. Biediger RJ. Boatman D. Shindo M. Smith CC. Kim S. Nadizadeh H. Suzuki Y. Tao C. Vu P. Tang S. Zhang P. Murthi KK. Gentile LS. Liu JH. J. Am. Chem. Soc.  1994,  116:  1597 
  • 4b Holton RA. Kim HB. Somoza C. Liang F. Biediger RJ. Boatman D. Shindo M. Smith CC. Kim S. Nadizadeh H. Suzuki Y. Tao C. Vu P. Tang S. Zhang P. Murthi KK. Gentile LS. Liu JH. J. Am. Chem. Soc.  1994,  116:  1599 
  • 5 Nicolaou KC. Zang Z. Liu JJ. Ueno H. Nantermet PG. Guy RK. Claiborne CF. Renaud J. Couladouros EA. Paulvannan K. Sorensen EJ. Nature (London)  1994,  367:  630 
  • 6a Nicolaou KC. Yang Z. Shi G.-Q. Gunzner JL. Agrios KA. Gartner P. Nature (London)  1998,  392:  264 
  • 6b Nicolaou KC. Bunnage ME. McGarry DG. Shi S. Somers PK. Wallace PA. Chu X.-J. Agrios KA. Gunzner JL. Yang Z. Chem. Eur. J.  1999,  5:  599 
  • 6c Nicolaou KC. Wallace PA. Shi S. Ouellette MA. Bunnage ME. Gunzner JL. Agrios KA. Shi G.-Q. Gartner P. Yang Z. Chem. Eur. J.  1999,  5:  618 
  • 6d Nicolaou KC. Shi G.-Q. Gunzner JL. Gartner P. Wallace PA. Ouellette MA. Shi S. Bunnage ME. Agrios KA. Veale CA. Hwang C.-K. Hutchinson J. Prasad CVC. Ogilvie WW. Yang Z. Chem. Eur. J.  1999,  5:  628 
  • 6e Nicolaou KC. Gunzner JL. Shi G.-Q. Agrios KA. Gartner P. Yang Z. Chem. Eur. J.  1999,  5:  646 
  • 7 Goodman J. Walsh V. In The Story of Taxol: Nature and Politics in the Pursuit of an Anticancer Drug   Cambridge University Press; New York: 2001. 
  • 8 Suffness M. Wall ME. In Taxol: Science and Applications   Suffness M. CRC Press; Boca Raton, FL: 1995.  p.3-25  
  • 9 Wani MC. Taylor HL. Wall ME. Coggon P. McPhail AT. J. Am. Chem. Soc.  1971,  93:  2325 
  • 10a Taxane Anticancer Agents: Basic Science and Current Status   Georg GI. Chen TT. Ojima I. Vyas DM. ACS Symposium Series 583; Washington, DC: 1995. 
  • 10b Taxol Science and Applications   Suffness M. CRC Press; Boca Raton, FL: 1995. 
  • 10c Thigpen T. Vance RB. McGuire WP. Hoskins WJ. Brady M. Semin. Oncol.  1995,  22:  23-31  ; 6-Suppl. 14
  • 10d Paclitaxel (Taxol®): Current Practices and Future Directions in Breast Cancer Management, In Seminars in Oncology   1-Suppl. 1, Vol. 23:  Yarboro JW. Bornstein RS. Mastrangelo MJ. W. B. Saunders; Philadelphia PA: 1996. 
  • 10e Chemotherapy with Paclitaxel and Platinum Compounds: Current Status and Future Directions, Vol. 2: Head and Neck Cancer, Breast Cancer, Gynecologic Malignancies, and Other Tumor Types, In Semininars in Oncology   5-Suppl. 12, Vol. 22:  Yarboro JW. Bornstein RS. Mastrangelo MJ. W. B. Saunders; Philadelphia PA: 1995. 
  • 10f Rowinsky EK. Donehower RC. New Engl. J. Med.  1995,  332:  1004 
  • 11 Horwitz SB. Fant J. Schiff PB. Nature (London)  1979,  277:  665 
  • 12a Rowinsky EK. Cazenave LA. Donehower RC. J. Natl. Cancer Inst.  1990,  82:  1247 
  • 12b Chase M. The Wall Street Journal  1991,  117:  1 
  • 13 Clinical overview of the taxanes: Goldspiel BR. Pharmacotherapy  1997,  17:  110 
  • 14a Croteau R. Ketchum REB. Long RM. Kaspera R. Wildung MR. Phytochem. Rev.  2006,  5:  75 
  • 14b Thayer AM. Chem. Eng. News  2000,  78:  20 
  • 14c McCoy M. Chem. Eng. News  2004,  82:  12 
  • 15 Wall ME. Wani MC. Am. Chem. Soc. Symp. Ser.  1995,  583:  18 
  • 16 Wuts PGM. Curr. Opin. Drug Discovery Dev.  1998,  1:  329 
  • 17 Tabata H. Adv. Biochem. Engin. Biotechnol.  2004,  7:  1 
  • For reviews, see:
  • 18a Kingston DGI. Chem. Commun.  2001,  867 
  • For reviews on synthetic studies, see:
  • 18b Wender PA. Natchus MG. Shuker AJ. In Taxol: Science and Applications   Suffness M. CRC Press; New York: 1995.  p.123-187  
  • 18c Boa AN. Jenkins PR. Lawrence NJ. Contemp. Org. Synth.  1994,  1:  47 
  • 18d Nicolaou KC. Dai WM. Guy RK. Angew. Chem., Int. Ed. Engl.  1994,  33:  15 
  • 18e Kingston DGI. Molinero AA. Rimoldi JM. Progress in the Chemistry of Organic Natural Products   Vol. 61:  Springer; New York: 1993. 
  • 18f Swindell CS. Org. Prep. Proced. Int.  1991,  23:  465 
  • 19a Chauviere G. Guenard D. Picot F. Senilh V. Potier P. C. R. Seances Acad. Sci., Ser. 2  1981,  293:  501 
  • 19b Croom EM. In Taxol: Science and Applications   Suffness M. CRC Press; Boca Raton FL: 1995.  p.37-70  
  • 19c Kikuchi Y. Yatagai M. In Taxus - The Genus Taxus   Itokawa H. Lee K.-H. Taylor & Francis; London: 2003.  p.151-178  
  • 20a Gibson DM. Ketchum REB. Hirasuna TJ. Shuler ML. In Taxol: Science and Applications   Suffness M. CRC Press; Boca Raton, FL: 1995.  p.71-95  
  • 20b Takeya K. In Taxus - The Genus Taxus   Itokawa H. Lee K.-H. Taylor & Francis; London: 2003.  p.134-150  
  • 21a Danishefsky SJ. Masters JJ. Young WB. Link JT. Snyder LB. Magee TV. Jung DK. Isaacs RCA. Bornmann WG. Alaimo CA. Coburn CA. Di Grandi MJ. J. Am. Chem. Soc.  1996,  118:  2843 
  • 21b Masters JJ. Link JT. Snyder LB. Young WB. Danishefsky SJ. Angew. Chem., Int. Ed. Engl.  1995,  34:  1723 
  • 22a Wender PA. Badham NF. Conway SP. Floreancig PE. Glass TE. Granicher C. Houze JB. Janichen J. Lee D. Marquess DG. McGrane PL. Meng W. Mucciaro TP. Muhlebach M. Natchus MG. Paulsen H. Rawlins DB. Satkofsky J. Shuker AJ. Sutton JC. Taylor RE. Tomooka K. J. Am. Chem. Soc.  1997,  119:  2755 
  • 22b 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. J. Am. Chem. Soc.  1997,  119:  2757 
  • 23a Kusama H. Hara R. Kawahara S. Nishimori T. Kashima H. Nakamura N. Morihira K. Kuwajima I. J. Am. Chem. Soc.  2000,  122:  3811 
  • 23b Morihira K. Hara R. Kawahara S. Nishimori T. Nakamura N. Kusama H. Kuwajima I. J. Am. Chem. Soc.  1998,  120:  12980 
  • 24 Mukaiyama T. Shiina I. Iwadare H. Saitoh M. Nishimura T. Ohkawa N. Sakoh H. Nishimura K. Tani Y.-I. Hasegawa M. Yamada K. Saitoh K. Chem. Eur. J.  1999,  5:  121 
  • 26a Wender PA. Bi FC. Gamber GG. Gosselin F. Hubbard RD. Scanio MJC. Sun R. Williams TJ. Zhang L. Pure Appl. Chem.  2002,  74:  25 
  • 26b Wender PA. Handy ST. Wright DL. Chem. Ind. (London)  1997,  765 
  • 26c Wender PA. Miller BL. Organic Synthesis: Theory and Applications   Vol. 2:  Hudlicky T. JAI; Greenwich: 1993.  p.27-66  
  • 27 Kurzweil R. In The Age of Spiritual Machines   Peguin; New York: 1999. 
  • For selected reviews, see:
  • 28a Welzel P. Chem. Rev.  2005,  105:  4610 
  • 28b Floss HG. Yu T.-W. Chem. Rev.  2005,  105:  621 
  • 28c Chatterjee C. Paul M. Xie L. van der Donk WA. Chem. Rev.  2005,  105:  633 
  • 28d Staunton J. Weissman KJ. Nat. Prod. Rep.  2001,  18:  380 
  • 28e Khosla C. Gokhale RS. Jacobsen JR. Cane DE. Annu. Rev. Biochem.  1999,  68:  219 
  • 28f Townsend CA. Chem. Biol.  1997,  4:  721 
  • 28g Roessner CA. Scott AI. Annu. Rev. Microbiol.  1996,  50:  467 
  • 29 Jennewein S. Park H. DeJong JM. Long RM. Bollon AP. Croteau RB. Biotechnol. Bioeng.  2005,  89:  588 ; and references therein
  • 30 Bruggink A. Schoevaart R. Kieboom T. Org. Process Res. Dev.  2003,  7:  622 
  • 32 Mikami K. Matsukawa S. Nagashima M. Funabashi H. Morisima H. Tetrahedron. Lett.  1997,  38:  579 
  • 33a Mikami K. Terada M. Motoyama Y. Nakai T. Tetrahedron: Asymmetry  1991,  2:  643 
  • 33b Mikami K. Motoyama Y. Terada M. J. Am. Chem. Soc.  1994,  116:  2812 
  • 34a Kondakov D. Negishi E. J. Am. Chem. Soc.  1995,  117:  10771 
  • 34b Kondakov D. Negishi E. J. Am. Chem. Soc.  1996,  118:  1577 
  • 34c Huo S. Negishi E. Org. Lett.  2001,  3:  3253 
  • 34d Huo S. Shi J. Negishi E. Angew. Chem. Int. Ed.  2002,  41:  2141 
  • 34e Negishi E. In Catalytic Asymmetric Synthesis II   Ojima I. Wiley-VCH; New York: 2000.  p.165 ; and references therein
  • 35 Novak T. Tan Z. Liang B. Negishi E. J. Am. Chem. Soc.  2005,  127:  2838 
  • 36 Doyle MP. McKervey MA. Ye T. In Modern Catalytic Methods for Organic Synthesis with Diazo Compounds   Wiley-Interscience; New York: 1998. 
  • 37a Davies HML. Beckwith REJ. Chem. Rev.  2003,  103:  2861 
  • 37b Davies HML. Loe O. Synthesis  2004,  2595 
  • 38a Davies HML. Jin Q. Org. Lett.  2004,  6:  1769 
  • 38b Davies HML. Jin Q. Org. Lett.  2005,  7:  2293 
  • 39 Gillingham DG. Hoveyda AH. Angew. Chem. Int. Ed.  2007,  46:  3860 
  • 40 For a review on Iminium catalysis, see: Lelais G. MacMillan DWC. Aldrichimica Acta  2006,  39:  79 
  • 41 Paras NA. MacMillan DWC. J. Am. Chem. Soc.  2001,  123:  4370 
  • 42a Kulpinski MS. Nord FF. J. Org. Chem.  1943,  8:  256 
  • 42b Villiani FJ. Nord FF. J. Am. Chem. Soc.  1946,  68:  1674 
  • 42c Villiani FJ. Nord FF. J. Am. Chem. Soc.  1947,  69:  2605 
  • 43 Mascarenhas CM. Miller SP. White PS. Morken JP. Angew. Chem. Int. Ed.  2001,  40:  601 
  • 44 Gnanadesikan V. Horiuchi Y. Ohshima T. Shibasaki M. J. Am. Chem. Soc.  2004,  126:  7782 
  • 45a Yamada YMA. Yoshikawa N. Sasai H. Shibasaki M. Angew. Chem., Int. Ed. Engl.  1997,  36:  1871 
  • 45b Yoshikawa N. Yamada YMA. Das J. Sasai H. Shibasaki M. J. Am. Chem. Soc.  1999,  121:  4168 
  • 45c Yoshikawa N. Kumagai N. Matsunaga S. Moll G. Ohshima T. Suzuki T. Shibasaki M. J. Am. Chem. Soc.  2001,  123:  2466 
  • 46 Tian J. Yamagiwa N. Shigeki M. Shibasaki M. Angew. Chem. Int. Ed.  2002,  41:  3636 
  • 47a Tomioka K. Nagaoka Y. In Comprehensive Asymmetric Catalysis   Vol. 3:  Jacobsen EN. Pfaltz A. Yamamoto H. Springer; Berlin: 1999.  p.1105 
  • 47b Krause N. Hoffmann-Röder A. Synthesis  2001,  171 
  • 47c Feringa BL. Naasz R. Imbos R. Arnold LA. In Modern Organocopper Chemistry   Krause N. Wiley-VCH; Weinheim: 2002.  p.224 
  • 47d Alexakis A. Benhaim C. Eur. J. Org. Chem.  2002,  3221 
  • 47e Hayashi T. Yamasaki K. Chem. Rev.  2003,  103:  2829 
  • 48a Cauble DF. Gipson DF. Krische MJ. J. Am. Chem. Soc.  2003,  125:  1110 
  • 48b Bocknack BM. Wang L.-C. Krische MJ. Proc. Natl. Acad. Sci. U. S. A.  2004,  101:  5421 
  • 49 Presented in full March 1st, 2004, Lilly Symposium, Indianapolis, USA; BASF Symposium on Molecular Catalysis, July 8th, 2005; Heidelberg, Germany, October 10th, 2005, SFB Symposium Aachen, Germany, and on a number of other occasions. Manuscript publication: Huang Y. Walji AM. Larsen CH. MacMillan DWC. J. Am. Chem. Soc.  2005,  127:  15051 
  • 50 Marigo M. Schulte T. Franzén J. Jørgensen KA. J. Am. Chem. Soc.  2005,  127:  15710 
  • 51a Enders D. Hüttl MRM. Grondal C. Raabe G. Nature (London)  2006,  441:  861 
  • 51b Grondal C. Presentation of PhD studies   Princeton University; USA: 2007. 
  • 52 Ouellet SG. Tuttle JB. MacMillan DWC. J. Am. Chem. Soc.  2005,  127:  32 
  • 53 Beeson TD. MacMillan DWC. J. Am. Chem. Soc.  2005,  127:  8826 
  • 54a Enders D. Grondal C. Hüttl MRM. Angew. Chem. Int. Ed.  2007,  46:  2 
  • 54b List B. Chem. Commun.  2006,  819 
25

This number is based on collective discussions with Paul Reider and Mike Martinelli, Amgen Pharmaceuticals and Malcolm MacCoss, Merck Pharmaceuticals.

31

Given that this review is focused on the use of multiple catalytic cycles to generate complexity, we have restricted this discussion to cascade catalytic sequences that incorporate more than one asymmetric induction event.