Total Synthesis of 4-Ketoclonostachydiol

Abstract

A facile total synthesis of nonsymmetrical 14-membered macrocyclic bis-lactone, 4-ketoclonostachydiol has been demonstrated in a convergent approach. The synthetic strategy has been unambiguously successful towards incorporating all the three stereogenic centers present in the molecule with an overall yield of 0.9%. The key synthetic step includes MacMillan hydroxylation and Grubbs ring-closing metathesis reactions to furnish the core skeleton.

Key words

marine natural product - 14-membered macrocycle - clonostachydiol - Grubbs II catalyst - total synthesis

• References

• 1a MacMillan J, Simpson TJ. J. Chem. Soc., Perkin Trans. 1 1973; 1487
• 1b Amstrutz R, Hngerbuhler E, Seebach D. Helv. Chim. Acta 1981; 64: 1796
• 1c Grabley S, Hammann P, Thiericke R, Wink J, Philipps S, Zeeck A. J. Antibiot. 1993; 46: 343
• 1d Rao AV. R, Murthy VS, Sharma GV. M. Tetrahedron Lett. 1995; 36: 139
• 1e Sharma GV. M, Mallesham S, Chandra Mouli Ch. Tetrahedron: Asymmetry 2009; 20: 2513
• 2 Blunt JW, Copp BR, Munro MH. G, Northcote PT, Prinsep MR. Nat. Prod. Rep. 2005; 22: 15
• 3 Lang G, Mitova MI, Ellis G, Sar S, Phipps RK, Blunt JW, Cummings NJ, Cole AL. J, Munro MH. J. Nat. Prod. 2006; 69: 621
• 4 Kano C, Adachi K, Shizusato Y. Japanese patent JP 5247737, 2005
• 5 Han J, Su Y, Jiang T, Xu Y, Huo X, She X, Pan X. J. Org. Chem. 2009; 74: 3930
• 6 Yadav JS, Swamy T, Subba Reddy BV. Synlett 2008; 2773
• 7a Yadav JS, Reddy UV. S, Reddy BV. S. Tetrahedron Lett. 2009; 50: 5984
• 7b Sabitha G, Padmaja P, Reddy PN, Yadav JS. Tetrahedron Lett. 2010; 51: 6166
• 8a Brown SP, Brochu MP, Sinz CJ, MacMillian DW. C. J. Am. Chem. Soc. 2003; 125: 10808
• 8b Mangion IK, MacMillan DW. C. J. Am. Chem. Soc. 2005; 127: 3696
• 8c Chandrasekhar S, Mahipal B, Kavitha M. J. Org. Chem. 2009; 74: 9531
• 9 Narasaka K, Ukaji Y, Watanabe K. Bull. Chem. Soc. Jpn. 1987; 60: 1457
• 10 Show K, Gupta P, Kumar P. Tetrahedron: Asymmetry 2011; 22: 1212
• 11 Palik M, Karlubikova O, Lasikova A, Kozisek J, Gracza T. Eur. J. Org. Chem. 2009; 709
• 12 Sabitha G, Bhaskar VS, Reddy SS, Yadav JS. Tetrahedron 2008; 64: 10207
• 13 Prasad KR, Gandi VR. Tetrahedron: Asymmetry 2011; 22: 499
• 14 Ishihara K, Kawaguchi T, Matsuya Y, Sakurai H, Saiki I, Nemoto H. Eur. J. Org. Chem. 2004; 3973
• 15 Sasai H, Shibasaki M. Tetrahedron Lett. 1987; 28: 333
• 16 Hunter TJ, O’Doherty GA. Org. Lett. 2002; 4: 4447
• 17 Krishna PK, Ramana DV, Reddy BK. Synlett 2009; 2924
• 18 Deiters A, Martin S. Chem. Rev. 2004; 104: 2199