Enantioselective Synthesis of Altohyrtin C (Spongistatin 2): Synthesis of the AB- and CD-Spiroketal Subunits

Angewandte Chemie (International Edition in English)

Volumn 36, Issue 24, 1997, Pages 2738-2741

  Evans, David A ^a   Coleman, Paul J ^a   Dias, Luiz Carlos ^a  

^a HARVARD UNIVERSITY   (United States)

Author keywords

Altohyrtin; Antitumor agents; Natural products; Spongistatin; Total synthesis

Indexed keywords

EID: 0032491776     PISSN: 05700833     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.199727381     Document Type: Article

References (50)

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9. Abbreviations: dr=diastereomer ratio; TBS=tert-butyldimethylsilyl; TES=triethylsilyl; TMS=trimethylsilyl; DIBALH=diisobutylaluminum hydride; Np=2-naphthyl; TBAF=tetrabutylammonium fluoride: Tr=trityl=triphenylmethyl; Tf=trifluoromethanesulfonyl; Bn=benzyl; PPTS=pyridinium p-toluenesulfonate; CSA=camphorsulfonic acid; LDBB=di-tert-butylbiphenyllithium.
10. Synthetic approaches to the AB spiroketal: a) M. M. Claffey, C. H. Heathcock, J. Org. Chem. 1996, 61, 7646-7647; b) I. Paterson, R. M. Oballa, R. D. Norcross, Tetrahedron Lett. 1996, 37, 8581-8584; (c) L. A. Paquette, D. Zuev, ibid. 1997, 38, 5115-5118.
11. Synthetic approaches to the AB spiroketal: a) M. M. Claffey, C. H. Heathcock, J. Org. Chem. 1996, 61, 7646-7647; b) I. Paterson, R. M. Oballa, R. D. Norcross, Tetrahedron Lett. 1996, 37, 8581-8584; (c) L. A. Paquette, D. Zuev, ibid. 1997, 38, 5115-5118.
12. Synthetic approaches to the AB spiroketal: a) M. M. Claffey, C. H. Heathcock, J. Org. Chem. 1996, 61, 7646-7647; b) I. Paterson, R. M. Oballa, R. D. Norcross, Tetrahedron Lett. 1996, 37, 8581-8584; (c) L. A. Paquette, D. Zuev, ibid. 1997, 38, 5115-5118.
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27. 5 acetate.
28. Similar alkylmetal additions to AB spiroketones have been documented; see reference 5.
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32. D. A. Evans, B. W. Trotter, B. Côté, P. J. Coleman, L. C. Dias, and A. Tyler, Angew. Chem. 1997, 109, 2957-2961; Angew. Chem. Int. Ed. Engl. 1997, 36, 2744-2747.
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34. Synthetic approaches to the CD spiroketal: a) C. J. Hayes, C. H. Heathcock, J. Org. Chem. 1997, 62, 2678-2679; b) L. A. Paquette, A. Braun, Tetrahedron Lett. 1997, 38, 5119-5122.
35. Synthetic approaches to the CD spiroketal: a) C. J. Hayes, C. H. Heathcock, J. Org. Chem. 1997, 62, 2678-2679; b) L. A. Paquette, A. Braun, Tetrahedron Lett. 1997, 38, 5119-5122.
36. (R)-Trityl glycidol was prepared in 95% ee by Sharpless asymmetric epoxidation of allyl alcohol and in situ tritylation. Recrystallization provided the enantiomerically enriched compound: H. S. Hendrickson, E. K. Hendrickson, Chemistry and Physics of Lipids, 1990, 53, 115-120.
37. Under these reaction conditions, aldehyde 26 has no preferred diastereoface. Coupling of methyl ketone 25 with the antipode of 26 under the same reaction conditions also gives a 1,5-anti product.
38. The diastereoselectivity for this methyl ketone aldol coupling is 9.6:1 at -78°C. At -110°C, the diastereoselectivity increases to 22:1. a) D. A. Evans, P.J. Coleman, B. Cote, J. Org. Chem. 1997, 62, 788-789; b) I. Paterson, K. R. Gibson, R. M. Oballa, Tetrahedron Lett. 1996, 37, 8585-8588.
39. The diastereoselectivity for this methyl ketone aldol coupling is 9.6:1 at -78°C. At -110°C, the diastereoselectivity increases to 22:1. a) D. A. Evans, P.J. Coleman, B. Cote, J. Org. Chem. 1997, 62, 788-789; b) I. Paterson, K. R. Gibson, R. M. Oballa, Tetrahedron Lett. 1996, 37, 8585-8588.
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42. 21 methyl ether to give an α,β unsaturated ketone.
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44. 26ax)=11 Hz); 30: δ=3.9 ppm (t, J=3.2 Hz).
45. Due to the sensitivity of spiroketal substrate 29 to acidic media, equilibration experiments were kept short (1-3h). In dichloromethane/CSA, 29 equilibrated to a 1:1 (29:30) mixture of spiroisomers after 3 h.
46. 25 hydroxyl is assisting in the equilibration to afford 30 by participating in an internal chelate with the metal cation and proximally positioned anomeric oxygen. For related cases see a) D. R. Williams, P. A. Jass, R. D. Gaston, Tetrahedron Lett. 1993, 34, 3231-3234; b) M. J. Kurth, E. G. Brown, E. Hendra, H. Hope, J. Org. Chem. 1985, 50, 1115-1117; c) S. L. Schreiber, T. L. Sommer, K. Satake, Tetrahedron Lett. 1985, 26, 17-20.
47. 25 hydroxyl is assisting in the equilibration to afford 30 by participating in an internal chelate with the metal cation and proximally positioned anomeric oxygen. For related cases see a) D. R. Williams, P. A. Jass, R. D. Gaston, Tetrahedron Lett. 1993, 34, 3231-3234; b) M. J. Kurth, E. G. Brown, E. Hendra, H. Hope, J. Org. Chem. 1985, 50, 1115-1117; c) S. L. Schreiber, T. L. Sommer, K. Satake, Tetrahedron Lett. 1985, 26, 17-20.
48. 25 hydroxyl is assisting in the equilibration to afford 30 by participating in an internal chelate with the metal cation and proximally positioned anomeric oxygen. For related cases see a) D. R. Williams, P. A. Jass, R. D. Gaston, Tetrahedron Lett. 1993, 34, 3231-3234; b) M. J. Kurth, E. G. Brown, E. Hendra, H. Hope, J. Org. Chem. 1985, 50, 1115-1117; c) S. L. Schreiber, T. L. Sommer, K. Satake, Tetrahedron Lett. 1985, 26, 17-20.
49. J. M. Williams, R. B. Jobson, N. Yasuda, G. Marchesini, U. H. Dolling, E. J. Grabowski, Tetrahedron Lett. 1995, 36, 5461-5464.
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