Stereoselective Synthesis of the C27–C35 Eribulin Fragment and Its Utilization in Building Structurally Diverse Macrocycles

Abstract

A practical and scalable stereoselective synthesis of the western substituted tetrahydrofuran ring C27–C35 fragment of eribulin was developed by using (2S,3S)-tartaric acid as a cheap starting material that was converted into an intermediate through a stereoselective vinylation­ and cross-metathesis as the key steps. A regio- and stereo­selective intramolecular oxy-Michael cyclization or an iodocyclization reaction finally provided the required western tetrahydrofuran ring fragment and its related isomeric analogues. These key fragments were further utilized in obtaining several types of macrocyclic derivatives for exploration of their biological properties. The simplicity of our present approach has the potential to be considered for large-scale syntheses of key fragments of eribulin and related analogues.

Key words

halichondrins - eribulin - medicinal chemistry - macrocycles - natural products - stereoselective synthesis

• References

• 1 Ueda A, Yamamoto A, Kato D, Kishi Y. J. Am. Chem. Soc. 2014; 136: 5171
• 2 Yamamoto A, Ueda A, Brémond P, Tiseni PS, Kishi Y. J. Am. Chem. Soc. 2012; 134: 893
• 3 Shan M, Kishi Y. Org. Lett. 2012; 14: 660
• 4 Yang YR, Kim D.-S, Kishi Y. Org. Lett. 2009; 11: 4516
• 5 Kim D.-S, Dong C.-G, Kim J.-T, Guo H, Huang J, Tiseni PS, Kishi Y. J. Am. Chem. Soc. 2009; 131: 15636
• 6 Choi H.-w, Demeke D, Kang F.-A, Kishi Y, Nakajima K, Nowak P, Wan Z.-K, Xie C. Pure Appl. Chem. 2003; 75: 1
• 7 Morris JC, Phillips AJ. Nat. Prod. Rep. 2011; 28: 269
• 8 Jackson KL, Henderson JA, Phillips AJ. Chem. Rev. 2009; 109: 3044
• 9 Jackson KL, Henderson JA, Motoyoshi H, Phillips AJ. Angew. Chem. Int. Ed. 2009; 48: 2346
• 10 Nicholas GM, Phillips AJ. Nat. Prod. Rep. 2005; 22: 144
• 11 Burke SD, Jung KW, Lambert WT, Phillips JR, Klovning JJ. J. Org. Chem. 2000; 65: 4070
• 12 McBride A, Butler SK. Am. J. Health-Syst. Pharm. 2012; 69: 745
• 13 Belanger F, Chase CE, Endo A, Fang FG, Li J, Mathieu SR, Wilcoxen AZ, Zhang H. Angew. Chem. Int. Ed. 2015; 54: 5108
• 14 Yu MJ, Zheng W, Seletsky BM. Nat. Prod. Rep. 2013; 30: 1158
• 15 Swami U, Chaudhary I, Ghalib MH, Goel S. Crit. Rev. Oncol. Hematol. 2012; 81: 163
• 16 Preston JN, Trivedi MV. Ann. Pharmacother. 2012; 46: 802
• 17 Perry CM. Drugs 2011; 71: 1321 ; DOI: 10.2165/11207520-000000000-00000
• 18 Menis J, Twelves C. Breast Cancer (Dove Med. Press) 2011; 3: 101 ; DOI: 10.2147/BCTT.S21741
• 19 Jain S, Vahdat LT. Clin. Cancer Res. 2011; 17: 6615
• 20 Smith JA, Wilson L, Azarenko O, Zhu X, Lewis BM, Littlefield BA, Jordan MA. Biochemistry 2010; 49: 1331
• 21 Bai R, Nguyen TL, Burnett JC, Atasoylu O, Munro MH, Pettit GR, Smith 3rd AB, Gussio R, Hamel E. J. Chem. Inf. Model. 2011; 51: 1393
• 22 Alday PH, Correia JJ. Biochemistry 2009; 48: 7927
• 23 Okouneva T, Azarenko O, Wilson L, Littlefield BA, Jordan MA. Mol. Cancer Ther. 2008; 7: 2003
• 24 Narayan S, Carlson EM, Cheng H, Condon K, Du H, Eckley S, Hu Y, Jiang Y, Kumar V, Lewis BM, Saxton P, Schuck E, Seletsky BM, Tendyke K, Zhang H, Zheng W, Littlefield BA, Towle MJ, Yu MJ. Bioorg. Med. Chem. Lett. 2011; 21: 1634
• 25 Narayan S, Carlson EM, Cheng H, Condon K, Du H, Eckley S, Hu Y, Jiang Y, Kumar V, Lewis BM, Saxton P, Schuck E, Seletsky BM, Tendyke K, Zhang H, Zheng W, Littlefield BA, Towle MJ, Yu MJ. Bioorg. Med. Chem. Lett. 2011; 21: 1639
• 26 Jimmidi R, Guduru SK. R, Arya P. Org. Lett. 2015; 17: 468
• 27 Terrett N. New Sci. 2002; 174: 1
• 28 Driggers EM, Hale SP, Lee J, Terrett NK. Nat. Rev. Drug Discov. 2008; 7: 608
• 29 Yu X, Sun D. Molecules 2013; 18: 6230
• 30 Comer E, Liu H, Joliton A, Clabaut A, Johnson C, Akella LB, Marcaurelle LA. Proc. Natl. Acad. Sci. U.S.A. 2011; 108: 6751
• 31 Lewandowski B, Jarosz S. Org. Lett. 2010; 12: 2532
• 32 Hill TA, Shepherd NE, Diness F, Fairlie DP. Angew. Chem. Int. Ed. 2014; 53: 13020
• 33 Marsault E, Peterson ML. J. Med. Chem. 2011; 54: 1961
• 34 Guduru SK. R, Jimmidi R, Deora GS, Arya P. Org. Lett. 2015; 17: 480
• 35 Aeluri M, Dasari B, Arya P. Org. Lett. 2015; 17: 472
• 36 Jogula S, Dasari B, Khatravath M, Chandrasekar G, Kitambi SS, Arya P. Eur. J. Org. Chem. 2013; 5036
• 37 Guduru SK. R, Chamakuri S, Chandrasekar G, Kitambi SS, Arya P. ACS Med. Chem. Lett. 2013; 4: 666
• 38 Dasari B, Jogula S, Borhade R, Balasubramanian S, Chandrasekar G, Kitambi SS, Arya P. Org. Lett. 2013; 15: 432
• 39 Aeluri M, Pramanik C, Chetia L, Mallurwar NK, Balasubramanian S, Chandrasekar G, Kitambi SS, Arya P. Org. Lett. 2013; 15: 436