Synthesis of the C1–C13 Fragment of Mandelalide A

Abstract

This communication describes the synthesis of the fully functionalized C1 to C13 segment (southern part) of highly potent cytotoxic marine natural product mandelalide A. Pd-catalyzed oxa-­Michael cyclization followed by stereoselective reduction of the C7-ketone were carried out to construct the tetrahydropyran unit with required stereochemistry. The α,β-unsaturated ester moiety was constructed via cross-metathesis and the vinyl iodide was installed through modified Takai olefination.

Key words

mandelalide - oxa-Michael cyclization - modified Takai olefination - cross-metathesis

• References

• 1 Pallela R, Yoon N.-Y, Kim SK. Mar. Drugs 2010; 8: 1189
• 2 Kuttruff CA, Eastgate MD, Baron PS. Nat. Prod. Rep. 2014; 31: 419
• 3 Sikorska J, Hau AM, Anklin C, Parker-Nance S, Davies-Coleman MT, Ishmael JE, McPhail KL. J. Org. Chem. 2012; 77: 6066
• 4 Willwacher J, Fürstner A. Angew. Chem. Int. Ed. 2014; 53: 4217
• 5 Lei H, Yan J, Yu J, Liu Y, Wang Z, Xu Z, Ye T. Angew. Chem. Int. Ed. 2014; 53: 6533
• 6a Winder PL. Ph.D. Thesis . Florida Atlantic University; USA: 2009
• 6b Paterson I, Gregory HH. Org. Lett. 2013; 15: 1338
• 7 Willwacher J, Heggen B, Wirtz C, Thiel W, Fürstner A. Chem. Eur. J. 2015; 21: 10416
• 8a Reddy KM, Yamini V, Singarapu KK, Ghosh S. Org. Lett. 2014; 16: 2658
• 8b Athe S, Chandrasekhar B, Roy S, Pradhan TK, Ghosh S. J. Org. Chem. 2012; 77: 9840
• 8c Reddy KM, Shashidhar J, Pottireddygari GR, Ghosh S. Tetrahedron Lett. 2011; 52: 5987
• 8d Ghosh S, Pradhan TK. J. Org. Chem. 2010; 75: 2107
• 9 Sonogashira K, Tohda Y, Hagihara N. Tetrahedron Lett. 1975; 4467
• 10a Takai K, Nitta K, Utimoto K. J. Am. Chem. Soc. 1986; 108: 7408
• 10b Augé J, Boucard V, Gil R, Lubin-Germain N, Picard J, Uziel J. Synth. Commun. 2003; 33: 3733
• 11a Trnka TM, Grubbs RH. Acc. Chem. Res. 2001; 34: 18
• 11b Fürstner A. Angew. Chem. Int. Ed. 2000; 39: 3012
• 11c Cannon SJ, Blechert S. Angew. Chem. Int. Ed. 2003; 42: 1900
• 11d Chatterjee AK, Morgan JP, Scholl M, Grubbs RH. J. Am. Chem. Soc. 2000; 122: 3783
• 11e Lipshutz BH, Ghorai S, Boskovic ZV. Tetrahedron 2008; 64: 6949
• 11f Voigtritter K, Ghorai S, Lipshutz BH. J. Org. Chem. 2011; 76: 4697
• 12 Reiter M, Turner H, Gouverneur V. Chem. Eur. J. 2006; 12: 7190
• 13 Blanchette MA, Choy W, Davis JT, Essenfeld AP, Masamune S, Roush WR, Sakai T. Tetrahedron Lett. 1984; 25: 2183
• 14 Smith III AB, Minbiole KP, Verhoest PR, Schelhaas M. J. Am. Chem. Soc. 2001; 123: 10942
• 15 Ahmed A, Hoegenauer EK, Enev VS, Hanbauer M, Kahelig H, Ohler E, Mulzer J. J. Org. Chem. 2003; 68: 3026
• 16 Oikawa Y, Yoshioka T, Yonemitsu O. Tetrahedron Lett. 1982; 23: 885