Syntheses of Bioactive Natural Products and Natural-Product-Like Compounds Based on Their Key Structural Units

Dedicated to Professor Lewis N. Mander on the occasion of his 75^th birthday

Abstract

This account describes our recent efforts toward the syntheses of natural products and natural-product-like compounds. Developing new strategies based on the key structural unit present in a target molecule is our main focus in the journey leading to the total synthesis of natural products.

1 Introduction

2 Synthesis of Podophyllotoxin

3 Synthesis of Mesembrine

4 Synthesis of Hexahydropyrroloindole Alkaloids

5 Total Synthesis of Stenine

6 Synthesis of Brazilide A, Brazilin, and Aza-Brazilins

7 Synthesis of Important Structural Units Present in Natural Products and Pharmaceuticals

8 Summary

Key words

key structural unit - sequential reactions - total synthesis - natural products - natural-product-like compounds

• References

• 1 Biomimetic Organic Synthesis . Vol. 1. Poupon E, Nay B. Wiley-VCH; Weinheim: 2011: 1-956
• 2a Corey EJ. Angew. Chem. Int. Ed. 1991; 30: 455
• 2b Corey EJ, Cheng XM. The Logic of Chemical Synthesis . John Wiley & Sons; New York: 1989: 1-96
• 2c Corey EJ. Chem. Soc. Rev. 1988; 17: 111
• 3 Wilson RM, Danishefsky SJ. J. Org. Chem. 2007; 72: 4293
• 4 Sheldon RA, Arends I, Hanefeld U. Green Chemistry and Catalysis . Wiley-VCH; Weinheim: 2007: 1-433
• 5a Pan C, Zeng X, Guan Y, Jiang X, Li L, Zhang H. Synlett 2011; 425
• 5b Zhao Y, Zhou Y, Liang L, Yang X, Du F, Li L, Zhang H. Org. Lett. 2009; 11: 555
• 6a Saleem M, Kim HJ, Ali MS, Lee YS. Nat. Prod. Rep. 2005; 22: 696
• 6b Silverberg LJ, Dillon JL, Vemishetti P, Sleezer PD, Discordia RP, Hartung KB, Gao Q. Org. Process Res. Dev. 2000; 4: 34
• 6c Damayanthi Y, Lown JW. Curr. Med. Chem. 1998; 5: 205
• 6d Hande KR. Eur. J. Cancer 1998; 34: 1514 ; and references therein

For reviews, see:
• 7a Sellars JD, Steel PG. Eur. J. Org. Chem. 2007; 3815
• 7b Ward RS. Phytochem. Rev. 2004; 2: 391
• 7c Ward RS. Synthesis 1992; 719
• 7d Ward RS. Tetrahedron 1990; 46: 5029

For more recent syntheses of podophyllotoxin, see:
• 7e Ting CP, Maimone TJ. Angew. Chem. Int. Ed. 2014; 53: 3115
• 7f Takahashi M, Suzuki N, Ishikawa T. J. Org. Chem. 2013; 78: 3250
• 8 Wu Y, Zhang H, Zhao Y, Zhao J, Chen J, Li L. Org. Lett. 2007; 9: 1199
• 9a Alexakis A, Sedrani R, Mangeney P, Normant JF. Tetrahedron Lett. 1988; 29: 4411
• 9b Frey LF, Tillyer RD, Caille A.-S, Tschaen DM, Dolling U.-H, Grabowski EJ. J, Reider PJ. J. Org. Chem. 1998; 63: 3120
• 10a Agami C, Comesse S, Kadouri-Puchot C. J. Org. Chem. 2002; 67: 1496
• 10b Collum DB. Acc. Chem. Res. 1992; 25: 448
• 11 Wu Y, Zhao J, Chen J, Pan C, Li L, Zhang H. Org. Lett. 2009; 11: 597
• 12a Popelak A, Lettenbauer G In The Alkaloids : Chemistry and Physiology . Vol. 9. Manske RH. F. Academic Press; New York: 1967: 467-482

For reviews on the synthesis of mesembrine see:
• 12b Zhao Y, Zhou Y, Du F, Liang L, Zhang H. Chin. J. Org. Chem. 2010; 30: 47
• 12c Stevens RV, Wentland MP. J. Am. Chem. Soc. 1968; 90: 5580
• 12d For a very recent synthesis of mesembrine, see: Geoghegan K, Evans P. J. Org. Chem. 2013; 78: 3410

For recent reviews, see:
• 13a Kornienko A, Evidente A. Chem. Rev. 2008; 108: 1982
• 13b Somei M, Yamada F. Nat. Prod. Rep. 2005; 22: 73
• 13c Jin Z. Nat. Prod. Rep. 2005; 22: 111
• 13d Zezula J, Hudlicky T. Synlett 2005; 388
• 13e Somei M, Yamada F. Nat. Prod. Rep. 2004; 21: 278
• 14a Anthoni U, Christophersen C, Nielsen PH In Alkaloids: Chemical and Biological Perspectives . Vol. 13. Pelletier SW. Pergamon; London: 1999: 163-236
• 14b Hino T, Nakagawa M In The Alkaloids: Chemistry and Pharmacology . Vol. 34. Brossi A. Academic Press; New York: 1989: 1-75
• 14c For a recent review, see: Ruiz-Sanchis P, Savina SA, Albericio F, Álvarez M. Chem. Eur. J. 2011; 17: 1388

For selected recent syntheses of hexahydropyrrolo[2,3-b]indole alkaloids, see:
• 14d Lin A, Yang J, Hashim M. Org. Lett. 2013; 15: 1950
• 14e Zhang X, Yang Z.-P, Liu C, You S.-L. Chem. Sci. 2013; 4: 3239
• 14f Miyamoto H, Hirano T, Okawa Y, Nakazaki A, Kobayashi S. Tetrahedron 2013; 69: 9481
• 15a Matsuura T, Overman LE, Poon DJ. J. Am. Chem. Soc. 1998; 120: 6500
• 15b Ashimori A, Matsuura T, Overman LE, Poon DJ. J. Org. Chem. 1993; 58: 6949
• 16 Zhou Y, Zhao Y, Dai X, Liu J, Li L, Zhang H. Org. Biomol. Chem. 2011; 9: 4091
• 17 Zhou Y, Xi Y, Zhao J, Sheng X, Zhang S, Zhang H. Org. Lett. 2012; 14: 3116
• 18a A similar intermediate has been used for the synthesis of horsfiline, see: Trost BM, Brennan MK. Org. Lett. 2006; 8: 2027

For selected recent syntheses of esermethole, see:
• 18b Araki K, Ozawa T, Yokoe H, Kanematsu M, Yoshida M, Shishido K. Org. Lett. 2013; 15: 200
• 18c Zhan F, Liang G. Angew. Chem. Int. Ed. 2013; 52: 1266
• 19a Pilli RA, Ferreira de Oliveira Md. C. Nat. Prod. Rep. 2000; 17: 117
• 19b Pilli RA, Rosso GB, Ferreira de Oliveira Md. C In The Alkaloids: Chemistry and Biology . Vol. 62. Cordell GA. Academic Press; New York: 2005: 77-173
• 20 For a very recent review, see: Chen J, Chen J, Xie Y, Liu N, Liu D, Zhang H. Chin. J. Org. Chem. 2013; 33: 1186
• 21a Evans DA, Seidel D. J. Am. Chem. Soc. 2005; 127: 9958
• 21b Evans DA, Mito S, Seidel D. J. Am. Chem. Soc. 2007; 129: 11583
• 22 Chen J, Chen J, Xie Y, Zhang H. Angew. Chem. Int. Ed. 2012; 51: 1024
• 23a Robinson R. Bull. Soc. Chim. Fr. 1958; 125
• 23b Craig JC, Naik AR, Pratt R, Johnson E. J. Org. Chem. 1965; 30: 1573
• 23c Yamahara CF. J, Shimokawa T, Kinjo J, Tomimatsu T, Nohara T. Phytochemistry 1985; 24: 2403
• 23d Namikoshi M, Nakata H, Yamada H, Nagai M, Saitoh T. Chem. Pharm. Bull. 1987; 35: 2761
• 23e Kim DS, Baek N, Oh SP, Jung KY, Lee IS, Lee H.-K. Phytochemistry 1997; 46: 177
• 23f Yang BO, Ke C.-Q, He Z.-S, Yang Y.-P, Ye Y. Tetrahedron Lett. 2002; 43: 1731
• 24a Huang Y, Zhang J, Pettus TR. R. Org. Lett. 2005; 7: 5841
• 24b Yen C.-T, Nakagawa-Goto K, Hwang T.-L, Wu P.-C, Morris-Natschke S.-L, Lai W.-C, Bastow KF, Chang F.-R, Wu Y.-C, Lee K.-H. Bioorg. Med. Chem. Lett. 2010; 20: 1037
• 24c Davis FA, Chen B.-C. J. Org. Chem. 1993; 58: 1751
• 25 Wang X, Zhang H, Yang X, Zhao J, Pan C. Chem. Commun. 2013; 49: 5405
• 26 Liang J, Chen J, Du F, Zeng X, Li L, Zhang H. Org. Lett. 2009; 11: 2820
• 27 Xu Z, Huang K, Liu T, Xie M, Zhang H. Chem. Commun. 2011; 47: 4923
• 28a Liang J, Chen J, Liu J, Li L, Zhang H. Chem. Commun. 2010; 46: 3666
• 28b Pan Z, Liang J, Chen J, Yang X, Zhang H. Nat. Prod. Bioprospect. 2011; 1: 129
• 29a Tsuda Y, Nakai A, Ito K, Suzuki F, Haruna M. Heterocycles 1984; 22: 1817

For very recent syntheses of demethoxyerythratidinone, see:
• 29b Heller ST, Kiho T, Narayan AR. H, Sarpong R. Angew. Chem. Int. Ed. 2013; 52: 11129
• 29c Kalaitzakis D, Montagnon T, Antonatou E, Vassilikogiannakis G. Org. Lett. 2013; 15: 3714