Studies Directed Towards the Synthesis of Bryostatin: A Stereoselective Synthesis of the C7–C16 Fragment

Abstract

A stereocontrolled asymmetric synthesis of the C7–C16 fragment of bryostatins is described. The key steps involved were a Jacobsen’s hydrolytic kinetic resolution and a Reformatsky reaction to build the C11–C16 fragment. A vinyl Grignard reagent was used to construct the C7–C10 fragment. The C11–C16 and C7–C10 fragments were coupled by means of a cross-metathesis reaction to give a key intermediate. The pyran ring system was constructed by means of an oxa-Michael reaction.

Key words

heterocycles - stereoselective synthesis - medicinal chemistry - pyrans

• References

• 1a Pettit GR, Herald CL, Clardy J, Arnold E, Doubek DL, Herald DL. J. Am. Chem. Soc. 1982; 104: 6848
• 1b Pettit GR, Kamano Y, Herald CL, Tozawa M. J. Am. Chem. Soc. 1984; 106: 6768
• 2a Kraft AS. J. Natl. Cancer Inst. 1993; 85: 1790

For reviews, see:
• 2b Mohammad RM, Wall NR, Dutcher JA, Al Katib AM. Clin. Cancer. Res. 2000; 6: 4950
• 2c Stone RM. Leuk. Res. 1997; 21: 399
• 2d Kamano Y, Zhang HP, Hino A, Yoshida M, Pettit GR, Herald CL. Itokawa H. J. Nat. Prod. 1995; 58: 1868
• 3a Kageyama M, Tamura T, Nantz MH, Roberts JC, Somfai P, Whritenour DC, Masamune S. J. Am. Chem. Soc. 1990; 112: 7407
• 3b Blanchette MA, Malamas MS, Nantz MH, Roberts JC, Somfai P, Whritenour DC, Masamune S. J. Org. Chem. 1989; 54: 2817
• 3c Ma P, Martin VC, Masamune S, Sharpless KB, Viti SM. J. Org. Chem. 1982; 47: 1378
• 3d Masamune S, Sato T, Kim BM, Wollmann TA. J. Am. Chem. Soc. 1986; 108: 8279
• 4a Ohmori K, Ogawa Y, Obitsu T, Ishikawa Y, Nishiyama S, Yamamura S. Angew. Chem. Int. Ed. 2000; 39: 2290
• 4b Evans DA, Carter PH, Carreira EM, Charette AB, Prunet JA, Lautens M. J. Am. Chem. Soc. 1999; 121: 7540
• 4c Evans DA, Carter PH, Carreira EM, Prunet JA, Charette AB, Lautens M. Angew. Chem. Int. Ed. 1998; 37: 2354
• 4d Tanaka K, Ohta Y, Fuji K, Taga J. Tetrahedron Lett. 1993; 34: 4071
• 4e Lu Y, Woo SK, Krische MJ. J. Am. Chem. Soc. 2011; 133: 13876
• 4f Keck GE, Poudel YB, Cummins TJ, Rudra A, Covel JA. J. Am. Chem. Soc. 2011; 133: 744
• 4g Wender PA, Schrier JA. J. Am. Chem. Soc. 2011; 133: 9228
• 5a De Brabander J, Vandewalle M. Synthesis 1994; 855
• 5b Vacalopoulos A, Lampe TF. J, Hoffmann HM. R. Org. Lett. 2001; 3: 929
• 5c Weiss JM, Hoffmann HM. R. Tetrahedron: Asymmetry 1997; 8: 3913
• 5d Ball M, Baron A, Bradshaw B, Omori H, MacCormick S, Thomas EJ. Tetrahedron Lett. 2004; 45: 8737
• 5e O’Brien M, Taylor HN, Thomas EJ. Tetrahedron Lett. 2002; 43: 5491
• 5f Yadav JS, Bandopadhyay A, Kunwar AC. Tetrahedron Lett. 2001; 42: 4907
• 5g Keck GE, Welch DS, Poudel YB. Tetrahedron Lett. 2006; 47: 8267
• 6a Evans DA, Chapman KT, Carreira EM. J. Am. Chem. Soc. 1988; 110: 3560
• 6b Keck GE, Poudel YB, Welch DS, Kraft MB, Truong AP, Stephens JC, Kedei N, Lewin NE, Blumberg PM. Org. Lett. 2009; 11: 593
• 6c Keck GE, Truong AP. Org. Lett. 2005; 7: 2153
• 6d Keck GE, Kraft MB, Truong AP, Li W, Sanchez CC, Kedei N, Lewin NE, Blumberg PM. J. Am. Chem. Soc. 2008; 130: 6660
• 6e Keck GE, Li W, Kraft MB, Kedei N, Lewin NE, Blumberg PM. Org. Lett. 2009; 11: 2277
• 6f Wender PA, DeChristopher BA, Schrier AJ. J. Am. Chem. Soc. 2008; 130: 6658
• 7a Hale KJ, Hummersone MG, Bhatia GS. Org. Lett. 2000; 2: 2189
• 7b Hale KJ, Frigerio M, Manaviazar S. Org. Lett. 2003; 5: 503
• 7c Trost BM, Yang H, Thiel OR, Frontier AJ, Brindle CS. J. Am. Chem. Soc. 2007; 129: 2206

For reviews, see:
• 8a Connon SJ, Blechert S. Top. Organomet. Chem. 2004; 11: 93
• 8b Connon SJ, Blechert S. Angew. Chem. Int. Ed. 2003; 42, 1900
• 8c Ellis GW. L, Johnson CD, Rogers DN. J. Am. Chem. Soc. 1983; 105: 5090
• 8d Ellis GW. L, Johnson CD, Rogers DN. J. Chem. Soc., Chem. Commun. (Cambridge) 1982; 36
• 8e Evans DA, Carreira EM. Tetrahedron Lett. 1990; 31: 4703
• 8f Edmunds AJ. F, Trueb W. Tetrahedron Lett. 1997; 38: 1009
• 9a Byeon SR, Park H, Kim H, Hong J. Org. Lett. 2011; 13: 5816
• 9b Hajare AK, Ravikumar V, Khaleel S, Bhuniya D, Srinivas Reddy D. J. Org. Chem. 2011; 76: 963
• 9c Srihari P, Satyanarayana K, Ganganna B, Yadav JS. J. Org. Chem. 2011; 76: 1922
• 10 Dess DB, Martin JC. J. Am. Chem. Soc. 1991; 113: 7277
• 11a For a review on the Reformatsky reaction, see: Fürstner A. Synthesis 1989; 571
• 11b Zn was activated by sonication in 2–3% aq CuSO₄ or by treatment with 5% aq HCl: for general methods for Zn activation see: Ross NA, Bartsch RA. J. Org. Chem. 2003; 68: 360
• 12 Schaus SE, Brandes BD, Larrow JF, Tokunaga M, Hansen KB, Gould AE. Kurrow M. E, Jacobsen EN. J. Am. Chem. Soc. 2002; 124: 1307
• 13 Schwartz NN, Blumbergs JH. J. Org. Chem. 1964; 29: 1976
• 14 De Nooy AE. J, Besemer AC, van Bekkum H. Synthesis 1996; 1153 ; and references cited therein
• 15a Garner P, Park JM. J. Org. Chem. 1988; 53: 2979
• 15b Coleman RS, Carpenter AJ. Tetrahedron Lett. 1992; 33: 1697
• 15c Trost BM, Yang H, Wuitschik G. Org. Lett. 2005; 7: 4761