Tackling the Challenge of the Total Synthesis of Periploside A

Abstract

Periploside A is the prototypical congener of the pregnane glycosides occurring in the Chinese medicinal plant Periploca sepium, featuring a unique seven-membered formyl acetal bridged spiro-­orthoester (FABO) sugar linkage and potent immunosuppressive activities. This account details our efforts on the stereoselective construction of the FABO motif that has led to a successful total synthesis of peri­ploside A.

1 Introduction

2 Attempts at Construction of the FABO Motif

2.1 Intermolecular Condensation and Transacetalation

2.2 Intramolecular Hydrogen Atom Transfer (HAT) Reaction

3 Synthesis of the FABO Motif Bearing the Unnatural Anomeric Configuration

4 Synthesis of the FABO Motif Bearing the Natural Anomeric ­Configuration

4.1 Unsuccessful Attempts

4.2 Final Solution

5 Conclusion

Key words

orthoester - formacetal - deoxysaccharides - dioxocarbenium - conformation - pregnane glycosides - glycosylation

• References

• 1 Oshima Y. Hirota T. Hikino H. Heterocycles 1987; 26: 2093
• 2a Itokawa H. Xu JP. Takeya K. Watanabe K. Shoji J. Chem. Pharm. Bull. 1988; 36: 982
• 2b Itokawa H. Xu JP. Takeya K. Chem. Pharm. Bull. 1988; 36: 2084
• 2c Itokawa H. Xu JP. Takeya K. Chem. Pharm. Bull. 1988; 36: 4441
• 3a Feng J. Zhang R. Zhou Y. Chen Z. Tang W. Liu Q. Zuo J. Zhao W. Phytochemistry 2008; 69: 2716
• 3b Wang L. Chen Z. Zhou Y. Tang W. Zuo J. Zhao W. Phytochemistry 2011; 72: 2230
• 3c Wang L. Chen Z. Zhou Y. Tang W. Zuo J. Zhao W. Phytochemistry 2013; 95: 445
• 4a Wang L. Qin J. Chen Z. Zhou Y. Tang W. Zuo J. Zhao W. J. Nat. Prod. 2017; 80: 1102
• 4b Qin J. Lin Z. Xu Y. Ren J. Zuo J. Zhao W. Bioorg. Med. Chem. Lett. 2018; 28: 330
• 5a Zhu Y. Zhao W. Yang Y. Liu Q. Zhou Y. Tian J. Ni J. Fu Y. Zhong X. Tang W. Zhou R. He P. Li X. Zuo J. J. Pharmacol. Exp. Ther. 2006; 316: 662
• 5b Zhu Y. Zhong X. Feng J. Yang Y. Fu Y. Ni J. Liu Q. Tang W. Zhao W. Zuo J. J. Pharma­col. Exp. Ther. 2006; 318: 1153
• 5c Zhao W. Zuo J. Liu Q. Zhu Y. Zou J. Yang Y. Tian J. Zhou Y. WO2007036113A1, 2007
• 6 Zhang X. Ph.D. Thesis. University of Chinese Academy of Sciences; Beijing: 2015
• 7 Zhang X. Zhou Y. Zuo J. Yu B. Nat. Commun. 2015; 6: 5879
• 8a Li Y. Yang Y. Yu B. Tetrahedron Lett. 2008; 49: 3608
• 8b Li Y. Yang X. Liu Y. Zhu C. Yang Y. Yu B. Chem. Eur. J. 2010; 16: 1871
• 8c Ma Y. Li Z. Shi H. Zhang J. Yu B. J. Org. Chem. 2011; 76: 9748
• 8d Zhang J. Shi H. Ma Y. Yu B. Chem. Commun. 2012; 48: 8679
• 8e Zhu Y. Yu B. Angew. Chem. Int. Ed. 2011; 50: 8329
• 8f Tang Y. Li J. Zhu Y. Li Y. Yu B. J. Am. Chem. Soc. 2013; 135: 18396
• 8g Zhang S. Ma Y. Li J. Ma J. Yu B. Xie X. Proc. Natl. Acad. Sci. U.S.A. 2014; 111: 14571
• 8h Yu B. Acc. Chem. Res. 2018; 51: 507
• 9 Yu B. Sun J. Chem. Commun. 2010; 46: 4668
• 10 Liao S.-G. Chen H.-D. Yue J.-M. Chem. Rev. 2009; 109: 1092
• 11a Yoshimura J. Tamaru M. Carbohydr. Res. 1979; 72: C9
• 11b Horito S. Asano K. Umemura K. Hashimoto H. Yoshimura J. Carbohydr. Res. 1983; 121: 175
• 12a Ohtake H. Iimori T. Ikegami S. Tetrahedron Lett. 1997; 38: 3413
• 12b Ohtake H. Ichiba N. Ikegami S. J. Org. Chem. 2000; 65: 8164
• 13a Powell NA. Roush WR. Org. Lett. 2001; 3: 453
• 13b Savall BM. Blanchard N. Roush WR. Org. Lett. 2003; 5: 377
• 13c Durham TB. Blanchard N. Savall BM. Powell NA. Roush WR. J. Am. Chem. Soc. 2004; 126: 9307
• 14a Bodenbenner K. Liebigs Ann. Chem. 1959; 623: 183
• 14b Collins DJ. Downes LM. Jhingran AG. Rutschmann SB. Sharp GJ. Aust. J. Chem. 1989; 42: 1235
• 14c Collins DJ. Jhingran AG. Rutschmann SB. Aust. J. Chem. 1989; 42: 1769
• 15 Praly J.-P. Descotes G. Tetrahedron Lett. 1982; 23: 849
• 16a Martín A. Martín IP. Quintanal LM. Suárez E. Org. Lett. 2007; 9: 1785
• 16b Francisco CG. Herrera AJ. Kennedy AR. Martín A. Melián D. Martín IP. Quintanal LM. Suárez E. Chem. Eur. J. 2008; 14: 10369
• 17 Crich D. Yang F. Angew. Chem. Int. Ed. 2009; 48: 8896
• 18a Matteucci M. Tetrahedron Lett. 1990; 31: 2385
• 18b Jones RJ. Lin K.-Y. Milligan JF. Wadwani S. Matteucci M. J. Org. Chem. 1993; 58: 2983
• 18c Sawada D. Ito Y. Tetrahedron Lett. 2001; 42: 2501
• 19a Jaurand G. Beau J.-M. Sinaÿ P. J. Chem. Soc., Chem. Commun. 1982; 701
• 19b Beau J.-M. Jaurand G. Esnault J. Sinaÿ P. Tetrahedron Lett. 1987; 28: 1105
• 19c Trumtel M. Tavecchia P. Veyrières A. Sinaÿ P. Carbohydr. Res. 1990; 202: 257
• 20a Nicolaou KC. Mitchell HJ. Fylaktakidou KC. Suzuki H. Rodríguez RM. Angew. Chem. Int. Ed. 2000; 39: 1089
• 20b Nicolaou KC. Rodríguez RM. Fylaktakidou KC. Suzuki H. Mitchell HJ. Angew. Chem. Int. Ed. 1999; 38: 3340
• 20c Nicolaou KC. Mitchell HJ. Fylaktakidou KC. Rodríguez RM. Suzuki H. Chem. Eur. J. 2000; 6: 3116
• 21a Ayala L. Lucero CG. Romero JA. C. Tabacco SA. Woerpel KA. J. Am. Chem. Soc. 2003; 125: 15521
• 21b Chamberland S. Ziller JW. Woerpel KA. J. Am. Chem. Soc. 2005; 127: 5322
• 21c Yang MT. Woerpel KA. J. Org. Chem. 2009; 74: 545
• 22 Deslongchamps P. Stereoelectronic Effects in Organic Chemistry . Pergamon; New York: 1983: 209
• 23 One reviewer of this manuscript suggests that the preference of conformations of the seven-membered FABO rings (in 63 and 64) may be a factor determining the stereoselectivity if the orthoester formation reaction proceeds through a late stage (product-like) transition state.
• 24 Jürs S. Thiem J. Synthesis 2006; 2117
• 25a Pilgrim W. Murphy PV. Org. Lett. 2009; 11: 939
• 25b Fujiwara K. Suzuki Y. Koseki N. Aki Y.-i. Kikuchi Y. Murata S.-i. Yamamoto F. Kawamura M. Norikura T. Matsue H. Murai A. Katoono R. Kawai H. Suzuki T. Angew. Chem. Int. Ed. 2014; 53: 780
• 26a Yamada H. Nakatani M. Ikeda T. Marumoto Y. Tetra­hedron Lett. 1999; 40: 5573
• 26b Ikeda T. Yamada H. Carbohydr. Res. 2000; 329: 889
• 26c Yamada H. Tanigakiuchi K. Nagao K. Okajima K. Mukae T. Tetrahedron Lett. 2004; 45: 5615
• 26d Okada Y. Nagata O. Taira M. Yamada H. Org. Lett. 2007; 9: 2755
• 27a Lemieux RU. Morgan AR. Can. J. Chem. 1965; 43: 2205
• 27b Kiss J. Arnold W. Helv. Chim. Acta 1975; 58: 297
• 27c Tius MA. Bush-Petersen J. Tetrahedron Lett. 1994; 35: 5181
• 27d Hosoya T. Ohashi Y. Matsumoto T. Suzuki K. Tetrahedron Lett. 1996; 37: 663
• 27e Tamura S. Abe H. Matsuda A. Shuto S. Angew. Chem. Int. Ed. 2003; 42: 1021
• 27f Jensen HH. Bols M. Acc. Chem. Res. 2006; 39: 259
• 28a Crich D. Smith M. J. Am. Chem. Soc. 2001; 123: 9015
• 28b Lian G. Zhang X. Yu B. Carbohydr. Res. 2015; 403: 13