Collective Synthesis of Natural Products by Using Metathesis ­Cascade Reactions

Abstract

This account describes our laboratory’s latest endeavors toward the collective synthesis of natural products. An overview of the general strategy is presented together with several total syntheses developed by our group. These examples demonstrate the power of metathesis cascade reactions and biomimetic strategies for the collective synthesis of securinega alkaloids and humulanolides.

1 Introduction

2 Collective Synthesis: A Historical Perspective

3 Collective Synthesis in Our Laboratory

3.1 Metathesis Cascade Reactions

3.2 Collective Synthesis of Securinega Alkaloids

3.3 Collective Synthesis of Humulanolides

3.3.1. Total Synthesis of Racemic Asteriscunolide D

3.3.2. Asymmetric Total Syntheses of Humulanolides

4 Conclusions and Outlook

Key words

total synthesis - cascade reaction - biomimetic synthesis - metathesis - natural products

• References

• 1 Wöhler F. Ann. Phys. Chem. 1828; 12: 253
• 2 Woodward RB, Doering WE. J. Am. Chem. Soc. 1944; 66: 849
• 3 Jones SB, Simmons B, Mastracchio A, MacMillan DW. C. Nature 2011; 475: 183
• 4 Wang Y.-F, Shi Q.-W, Dong M, Kiyota H, Gu Y.-C, Cong B. Chem. Rev. 2011; 111: 7652
• 5 Flyer AN, Si C, Myers AG. Nature Chem. 2010; 2: 886
• 6a Ren W, Bian Y, Zhang Z, Shang H, Zhang P, Chen Y, Yang Z, Luo TP, Tang YF. Angew. Chem. Int. Ed. 2012; 51: 6984
• 6b Shang H, Liu J, Bao R, Cao Y, Zhao K, Xiao C, Zhou B, Hu L, Tang YF. Angew. Chem. Int. Ed. 2014; 53: 14494
• 7a Li H, Wang X, Hong B, Lei XG. J. Org. Chem. 2013; 78: 800
• 7b Zhang J, Wu J, Hong B, Ai W, Wang X, Li H, Lei XG. Nat. Commun. 2014; 5: 4614
• 7c Li H, Wang X, Lei XG. Angew. Chem. Int. Ed. 2012; 51: 491

For recent divergent and efficient syntheses of the lycopodium alkaloids, see:
• 7d Huo S.-H, Tu Y.-Q, Liu L, Zhang F.-M, Wang S.-H, Zhang X. Angew. Chem. Int. Ed. 2013; 52: 11373
• 7e Zeng C, Zhao J, Zhao G. ­Tetrahedron 2015; 71: 64
• 8 Wang J, Chen S.-G, Sun B.-F, Lin G.-Q, Shang Y.-J. Chem. Eur. J. 2013; 19: 2539
• 9 Yue G, Zhang Y, Fang L, Li C.-C, Luo T, Yang Z. Angew. Chem. Int. Ed. 2014; 53: 1837
• 10 Jiang S.-Z, Lei T, Wei K, Yang Y.-R. Org. Lett. 2014; 16: 5612

In collaboration with Yang and co-workers, we have recently finished several total syntheses of challenging and complex natural products possessing significant bioactivities, see:
• 11a Liu L.-Z, Han J.-C, Yue G.-Z, Li C.-C, Yang Z. J. Am. Chem. Soc. 2010; 132: 13608
• 11b Gong J, Lin G, Sun W, Li C.-C, Yang Z. J. Am. Chem. Soc. 2010; 132: 16745
• 11c Shi H, Fang L, Tan C, Shi L, Zhang W, Li C.-C, Luo T, Yang Z. J. Am. Chem. Soc. 2011; 133: 14944
• 11d Liu Q, Yue G, Wu N, Lin G, Li Y, Quan J, Li C.-C, Wang G, Yang Z. Angew. Chem. Int. Ed. 2012; 51: 12072
• 11e Liu G, Mei G, Chen R, Yuan H, Yang Z, Li C.-C. Org. Lett. 2014; 16: 4380
• 12a Mei G, Liu X, Qiao C, Chen W, Li C.-C. Angew. Chem. Int. Ed. 2015; 54: 1754
• 12b Mei G, Yuan H, Gu Y, Chen W, Chung L, Li C.-C. Angew. Chem. Int. Ed. 2014; 53: 11051
• 13 Wei H, Qiao C, Liu G, Yang Z, Li C.-C. Angew. Chem. Int. Ed. 2013; 52: 620
• 14 Han J.-C, Li F, Li C.-C. J. Am. Chem. Soc. 2014; 136: 13610
• 15a Nguyen ST, Johnson LK, Grubbs RH. J. Am. Chem. Soc. 1992; 114: 3974
• 15b Fu GC, Nguyen ST, Grubbs RH. J. Am. Chem. Soc. 1993; 115: 9856
• 15c Schwab P, France MB, Ziller JW, Grubbs RH. Angew. Chem. Int. Ed. 1995; 34: 2039
• 15d Schwab P, Grubbs RH, Ziller JW. J. Am. Chem. Soc. 1996; 118: 100
• 16a Diver ST, Giessert AJ. Chem. Rev. 2004; 104: 1317
• 16b Nicolaou KC, Edmonds DJ, Bulger PG. Angew. Chem. Int. Ed. 2006; 45: 7134
• 17 Kim S.-H, Bowden N, Grubbs RH. J. Am. Chem. Soc. 1994; 116: 10801

For selective reviews on the metathesis cascade reaction in total synthesis, see:
• 18a Nicolaou KC, Bulger PG, Sarlah D. Angew. Chem. Int. Ed. 2005; 44: 4490
• 18b Maifeld SV, Lee D. Chem. Eur. J. 2005; 11: 6118
• 18c Mori M. Adv. Synth. Catal. 2007; 349: 121

For reviews, see:
• 19a Snieckus V In The Alkaloids . Vol. 14. Manske RH. F. Academic Press; New York: 1973: 425
• 19b Beutler JA, Brubaker AN. Drugs Future 1987; 12: 957
• 19c Weinreb SM. Nat. Prod. Rep. 2009; 26: 758
• 19d Zhang W, Li J.-Y, Lan P, Sun P.-H, Wang Y, Ye W.-C, Chen W.-M. J. Chin. Pharm. Sci. 2011; 3: 203
• 20a Horii Z, Hanaoka M, Yamawaki Y, Tamura Y, Saito S, Shigematsu N, Kotera K, Yoshikawa H, Sato Y, Nakai H, Sugimoto N. Tetrahedron 1967; 23: 1165
• 20b Heathcock CH, von Geldern TW. Heterocycles 1987; 25: 75
• 20c Niu C, Liang X. Acta Pharmacol. Sin. 1988; 23: 347
• 20d Jacobi PA, Blum CA, DeSimone RW, Udodong UE. S. Tetrahedron Lett. 1989; 30: 7173
• 20e Jacobi PA, Blum CA, DeSimone RW, Udodong UE. S. J. Am. Chem. Soc. 1991; 113: 5384
• 20f Xi FD, Liang XT. Acta Pharmacol. Sin. 1992; 27: 349
• 20g Magnus P, Rodríguez-López J, Mulholland K, Matthews I. J. Am. Chem. Soc. 1992; 114: 382
• 20h Magnus P, Rodríguez-López J, Mulholland K, Matthews I. Tetrahedron 1993; 49: 8059
• 20i Honda T, Namiki H, Kudoh M, Watanabe N, Nagase H, Mizutani H. Tetrahedron Lett. 2000; 41: 5927
• 20j Han G, LaPorte MG, Folmer JJ, Werner KM, Weinreb SM. Angew. Chem. Int. Ed. 2000; 39: 237
• 20k Han G, LaPorte MG, Folmer JJ, Werner KM, Weinreb SM. J. Org. Chem. 2000; 65: 6293
• 20l Liras S, Davoren JE, Bordner J. Org. Lett. 2001; 3: 703
• 20m Honda T, Namiki H, Kudoh M, Nagase H, Mizutani H. Heterocycles 2003; 59: 169
• 20n Honda T, Namiki H, Kaneda K, Mizutani H. Org. Lett. 2004; 6: 87
• 20o Honda T, Namiki H, Watanabe M, Mizutani H. Tetrahedron Lett. 2004; 45: 5211
• 20p Alibés R, Ballbé M, Busqué F, de March P, Elias L, Figueredo M, Font J. Org. Lett. 2004; 6: 1813
• 20q Alibés R, Bayón P, de March P, Figueredo M, Font J, García-García E, González-Gálvez D. Org. Lett. 2005; 7: 5107
• 20r Carson CA, Kerr MA. Angew. Chem. Int. Ed. 2006; 45: 6560
• 20s Liu P, Hong S, Weinreb SM. J. Am. Chem. Soc. 2008; 130: 7562
• 20t Leduc AB, Kerr MA. Angew. Chem. Int. Ed. 2008; 47: 7945
• 20u Bardají GG, Cantó M, Alibés R, Bayón P, Busqué F, de March P, Figueredo M, Font J. J. Org. Chem. 2008; 73: 7657
• 20v Dhudshia B, Cooper BF. T, Macdonald CL. B, Thadani AN. Chem. Commun. 2009; 463
• 20w González-Gálvez D, García-García E, Alibés R, Bayón P, de March P, Figueredo M, Font J. J. Org. Chem. 2009; 74: 6199
• 20x Medeiros MR, Wood JL. Tetrahedron 2010; 66: 4701
• 20y Sampath M, Lee P.-YB, Loh T.-P. Chem. Sci. 2011; 2: 1988
• 20z Bélanger G, Dupuis M, Larouche-Gauthier R. J. Org. Chem. 2012; 77: 3215
• 20aa Chen J, Levine SR, Buergler JF, McMahon TC, Medeiros MR, Wood JL. Org. Lett. 2012; 14: 4531
• 20ab Reddy AS, Srihari P. Tetrahedron Lett. 2012; 53: 5926
• 20ac ElSohly AM, Wespe DA, Poore TJ, Snyder SA. Angew. Chem. Int. Ed. 2013; 52: 5789
• 20ad Ma N, Yao Y, Zhao B, Wang Y, Ye W, Jiang S. Chem. Commun. 2014; 50: 9284
• 21a Zhao B.-X, Wang Y, Zhang D.-M, Jiang R.-W, Wang G.-C, Shi J.-M, Huang X.-J, Chen W.-M, Che C.-T, Ye W.-C. Org. Lett. 2011; 13: 3888
• 21b Zhao B.-X, Wang Y, Zhang D.-M, Huang X.-J, Bai L.-L, Yan Y, Chen J.-M, Lu T.-B, Wang Y.-T, Zhang Q.-W, Ye W.-C. Org. Lett. 2012; 14: 3096
• 22 For a review on enyne metathesis, see: Poulsen CS, Madsen R. Synthesis 2003; 1 ; see also ref. 18
• 23 During Honda’s synthesis of securinine, a similar RCM strategy was applied. However, in the presence of the less reactive conjugated ester, none of the desired product could be isolated. See: Honda T, Namiki H, Kaneda K, Mizutani H. Org. Lett. 2004; 6: 87
• 24a Hoye TR, Jeffrey CS, Tennakoon MA, Wang J, Zhao H. J. Am. Chem. Soc. 2004; 126: 10210
• 24b Wallace D. Angew. Chem. Int. Ed. 2005; 44: 1912
• 24c Wang X, Bowman EJ, Bowman BJ, Porco JA. Jr. Angew. Chem. Int. Ed. 2004; 43: 3601

For reviews on [3+2] cycloadditions of nitrones, see:
• 25a Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products. Padwa A, Pearson WH. Wiley; New York: 2003
• 25b Gothelf KV, Jørgensen KA. Chem. Rev. 1998; 98: 863
• 25c Cardona F, Goti A. Angew. Chem. Int. Ed. 2005; 44: 7832
• 25d Stanley LM, Sibi MP. Chem. Rev. 2008; 108: 2887
• 26 Kinoshita A, Mori M. Synlett 1994; 1020
• 27a Kim S.-H, Zuercher WJ, Bowden BB, Grubbs RH. J. Org. Chem. 1996; 61: 1073
• 27b Garber SB, Kingsbury JS, Gray BL, Hoveyda AH. J. Am. Chem. Soc. 2000; 122: 8168
• 27c Boyer F.-D, Hanna I, Ricard L. Org. Lett. 2001; 3: 3095
• 27d Boyer F.-D, Hanna I. Org. Lett. 2007; 9: 2293
• 27e Mukherjee S, Lee D. Org. Lett. 2009; 11: 2916
• 27f Park H, Hong Y.-L, Kim YB, Choi T.-L. Org. Lett. 2010; 12: 3442
• 27g Knüppel S, Rogachev VO, Metz P. Eur. J. Org. Chem. 2010; 6145
• 27h Schubert M, Metz P. Angew. Chem. Int. Ed. 2011; 50: 2954
• 28 Chang L, Jiang H, Fu J, Liu B, Li C.-C, Yang Z. J. Org. Chem. 2012; 77: 3609
• 29 Ulman M, Belderrain TR, Grubbs RH. Tetrahedron Lett. 2000; 41: 4689
• 30a Li J.-Y, Zhao B.-X, Zhang W, Li C, Huang X.-J, Wang Y, Sun P.-H, Ye W.-C, Chen W.-M. Tetrahedron 2012; 68: 3972
• 30b Nakano T, Terao S, Lee H, Saeki Y, Durham LJ. J. Org. Chem. 1966; 31: 2274
• 31 Tufariello JJ. Acc. Chem. Res. 1979; 12: 396 ; During Magnus’s pioneering synthesis of nirurine, a similar route was attempted; however, an unknown complex mixture was obtained. See ref. 20h
• 32 Negrín G, Eiroa JL, Morales M, Triana J, Quintana J, Estévez F. Mol. Carcinog. 2010; 49: 488
• 33 Rauter AP, Branco I, Bermejo J, González AG, García-Grávalos MD, San Feliciano A. Phytochemistry 2001; 56: 167
• 34a San Feliciano A, Barrero AF, Medarde M, Miguel del Corral JM, Ledesma E. Tetrahedron Lett. 1982; 23: 3097
• 34b San Feliciano A, Barrero AF, Medarde M, Miquel del Corral JM, Aramburu A, Sánchez-Ferrando F. Tetrahedron 1984; 40: 873
• 34c San Feliciano A, Barrero AF, Medarde M, Miguel del Corral JM, Aramburu A, Perales A, Fayos J, Sánchez-Ferrando F. Tetrahedron 1985; 41: 5711
• 35 Chaari A, Jannet HB, Mighri Z, Robinot C, Kunesch N. Nat. Prod. Lett. 2001; 15: 419
• 36a Corey EJ, Cheng X.-M. The Logic of Chemical Synthesis . Wiley; New York: 1995. Chap. 9.6 159

For an instructive strategy for the synthesis of zerumbone by using a Wittig-type reaction to construct the eleven-membered ring (3% yield) and in which the major product was formed by dimerization to give a 22-membered ring, see:
• 36b Kodama M, Shiobara Y, Sumitomo H, Mitani K, Ueno K. Chem. Pharm. Bull. 1987; 35: 4039
• 37 San Feliciano A, Barrero AF, Medarde M, Miguel del Corral JM, Aramburu A, Perales A, Fayos J. Tetrahedron Lett. 1985; 26: 2369
• 38 El Dahmy S, Jakupovic J, Bohlmann F, Sarg TM. Tetrahedron 1985; 41: 309
• 39 Akssira M, Mellouki F, Salhi A, Alilou H, Saouf A, El Hanbali F, Arteaga JF, Barrero AF. Tetrahedron Lett. 2006; 47: 6719
• 40a San Feliciano A, Medarde M, Miguel del Corral JM, Aramburu A, Gordaliza M, Barrero AF. Tetrahedron Lett. 1989; 30: 2851
• 40b Lodewyk MW, Soldi C, Jones PB, Olmstead MM, Rita J, Shaw JT, Tantillo DJ. J. Am. Chem. Soc. 2012; 134: 18550
• 41a Trost BM, Burns AC, Bartlett MJ, Tautz T, Weiss AH. J. Am. Chem. Soc. 2012; 134: 1474
• 41b Fernandes RA, Chavan VP. Chem. Commun. 2013; 49: 3354
• 42a Wender PA, Ihle NC, Correia CR. D. J. Am. Chem. Soc. 1988; 110: 5904
• 42b Paquette LA, Tae J, Arrington MP, Sadoun AH. J. Am. Chem. Soc. 2000; 122: 2742
• 42c Limanto J, Snapper ML. J. Am. Chem. Soc. 2000; 122: 8071
• 42d Kraft ME, Cheung Y.-Y, Juliano-Capucao CA. Synthesis 2000; 1020
• 42e Kraft ME, Cheung Y.-Y, Abboud KA. J. Org. Chem. 2001; 66: 7443
• 42f Liang Y, Jiang X, Yu Z.-X. Chem. Commun. 2011; 47: 6659
• 42g Liang Y, Jiang X, Fu X.-F, Ye S, Wang T, Yuan J, Wang Y, Yu Z.-X. Chem. Asian J. 2012; 7: 593
• 43a Pirrung MC. J. Org. Chem. 1987; 52: 1635
• 43b Mehta G, Murty AN. J. Org. Chem. 1990; 55: 3568
• 43c Booker-Milburn KI, Cowell JK, Harris LJ. Tetrahedron Lett. 1994; 35: 3883
• 43d Booker-Milburn KI, Cowell JK. Tetrahedron Lett. 1996; 37: 2177
• 43e Lange GL, Organ MG. J. Org. Chem. 1996; 61: 5358
• 43f Booker-Milburn KI, Cowell JK, Harris LJ. Tetrahedron 1997; 53: 12319
• 43g Sarkar TK, Gangopadhyay P, Ghorai BK. Nandy S. K, Fang J.-M. Tetrahedron 1998; 39: 8365
• 44a Storer RI, Takemoto T, Jackson PS, Brown DS, Baxendale IR, Ley SV. Chem. Eur. J. 2004; 10: 2529
• 44b Dieckmann M, Kretschmer M, Li P, Rudolph S, Herkommer D, Menche D. Angew. Chem. Int. Ed. 2012; 51: 5667

For selected studies on the use of transannular Michael reactions for natural product synthesis, see:
• 45a Shimizu I, Nakagawa H. Tetrahedron Lett. 1992; 33: 4957
• 45b Ergüden J.-K, Moore HW. Org. Lett. 1999; 1: 375
• 45c Matsuura T, Yamamura S. Tetrahedron Lett. 2000; 41: 4805
• 45d Snider BB, Zhou J. Org. Lett. 2006; 8: 1283
• 45e Scheerer JR, Lawrence JF, Wang GC, Evans DA. J. Am. Chem. Soc. 2007; 129: 8968
• 45f Xue H, Yang J, Gopal P. Org. Lett. 2011; 13: 5696
• 45g Li Y, Pattenden G. Tetrahedron 2011; 67: 10045
• 45h Gebauer K, Fürstner A. Angew. Chem. Int. Ed. 2014; 53: 6393
• 46a Mergott DJ, Frank SA, Roush WR. Proc. Natl. Acad. Sci. U. S. A. 2004; 101: 11955
• 46b Winbush SM, Mergott DJ, Roush WR. J. Org. Chem. 2008; 73: 1818

For recent reviews on the Morita–Baylis–Hillman reaction, see:
• 46c Wei Y, Shi M. Chem. Rev. 2013; 113: 6659
• 46d Basavaiah D, Reddy BS, Badsara SS. Chem. Rev. 2010; 110: 5447
• 47 Zuercher WJ, Hashimoto M, Grubbs RH. J. Am. Chem. Soc. 1996; 118: 6634

For selective works on tandem ROM/RCM, see:
• 48a Hart AC, Phillips AJ. J. Am. Chem. Soc. 2006; 128: 1094
• 48b Wrobleski A, Sahasrabudhe K, Aubé J. J. Am. Chem. Soc. 2002; 124: 9974
• 48c Chandler CL, Phillips AJ. Org. Lett. 2005; 7: 3493
• 48d Mori M, Wakamatsu H, Tonogaki K, Fujita R, Kitamura T, Sato Y. J. Org. Chem. 2005; 70: 1066
• 48e Malik CK, Yadav RN, Drew MG. B, Ghosh S. J. Org. Chem. 2009; 74: 1957

For the use of catalytic RCMs to prepare eleven-membered rings in syntheses of natural products, see:
• 49a Winkler JD, Holland JM, Kasparec J, Axelsen PH. Tetrahedron 1999; 55: 8199
• 49b Ronsheim MD, Zercher CK. J. Org. Chem. 2003; 68: 1878
• 49c Nicolaou KC, Montagnon T, Vassilikogiannakis G, Mathison CJ. N. J. Am. Chem. Soc. 2005; 127: 8872
• 49d Fürstner A, Müller C. Chem. Commun. 2005; 5583
• 49e Brown MK, Hoveyda AH. J. Am. Chem. Soc. 2008; 130: 12904
• 49f Cai Z, Yongpruksa N, Harmata M. Org. Lett. 2012; 14: 1661

For a brief overview of macrocyclization reactions through catalytic RCM, see:
• 49g Gradillas A, Pèrez-Castells J. Angew. Chem. Int. Ed. 2006; 45: 6086
• 50 Keitz BK, Endo K, Patel PR, Herbert MB, Grubbs RH. J. Am. Chem. Soc. 2012; 134: 693
• 51a Tang B, Bray CD, Pattenden G, Rogers J. Tetrahedron 2010; 66: 2492
• 51b Takao K, Nanamiya R, Fukushima Y, Namba A, Yoshida K, Tadano K. Org. Lett. 2013; 15: 5582
• 52 Compound 101 was prepared in good yield from the commercially available d-(–)-pantolactone by selective reduction with borane–tetrahydrofuran; see: Roy R, Rey AW. Can. J. Chem. 1991; 69: 62

For reviews on the synthesis of eight-membered carbocycles, see:
• 53a Lautens M, Klute W, Tam W. Chem. Rev. 1996; 96: 49
• 53b Mehta G, Singh V. Chem. Rev. 1999; 99: 881
• 53c Yet L. Chem. Rev. 2000; 100: 2963
• 53d Maier ME. Angew. Chem. Int. Ed. 2000; 39: 2073
• 53e Michaut A, Rodriguez J. Angew. Chem. Int. Ed. 2006; 45: 5740
• 53f Yu Z.-X, Wang Y, Wang Y. Chem. Asian J. 2010; 5: 1072

For recent reviews on protecting-group-free syntheses, see:
• 54a Young IS, Baran PS. Nat. Chem. 2009; 1: 193
• 54b Hoffmann RW. Synthesis 2006; 3531