Enantioselective Synthesis of Altohyrtin C (Spongistatin 2): Fragment Assembly and Revision of the Spongistatin 2 Stereochemical Assignment

Angewandte Chemie (International Edition in English)

Volumn 36, Issue 24, 1997, Pages 2744-2747

  Evans, David A ^a   Trotter, B Wesley ^a   Côté, Bernard ^a   Coleman, Paul J ^a   Dias, Luiz Carlos ^a   Tyler, Andrew N ^a  

^a HARVARD UNIVERSITY   (United States)

Author keywords

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

Indexed keywords

EID: 0032491845     PISSN: 05700833     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.199727441     Document Type: Article

References (27)

1. D. A. Evans, P. J. Coleman, L. C. Dias, Angew. Chem. 1997, 109, 2951-2954; Angew. Chem. Int. Ed. Engl. 1997, 36, 2738-2741.
2. D. A. Evans, P. J. Coleman, L. C. Dias, Angew. Chem. 1997, 109, 2951-2954; Angew. Chem. Int. Ed. Engl. 1997, 36, 2738-2741.
3. D. A. Evans, B. W. Trotter, B. Côté, P. J. Coleman, Angew. Chem. 1997, 109, 2954-2957; Angew. Chem. Int. Ed. Engl. 1997, 36, 2741-2744.
4. D. A. Evans, B. W. Trotter, B. Côté, P. J. Coleman, Angew. Chem. 1997, 109, 2954-2957; Angew. Chem. Int. Ed. Engl. 1997, 36, 2741-2744.
5. -1; b) R. Bai, G. F. Taylor, Z. A. Cichacz, C. L. Herald, J. A. Kepler, G. R. Pettit, E. Hamel, Biochemistry 1995, 34, 9714-9721: spongistatin 1 (X = Cl) 0.13nM, spongistatin 2 (X= H) 0.85nM.
6. -1; b) R. Bai, G. F. Taylor, Z. A. Cichacz, C. L. Herald, J. A. Kepler, G. R. Pettit, E. Hamel, Biochemistry 1995, 34, 9714-9721: spongistatin 1 (X = Cl) 0.13nM, spongistatin 2 (X= H) 0.85nM.
7. Abbreviations: dr=diastereomer ratio, 9-BBN=9-borabicyclo[3.3.1]nonane, cHex=cyclohexyl, TIPS=triisopropylsilyl, TBS=tert-butyldimethylsilyl, TES=triethylsilyl, TMS=trimethylsilyl, Tr=trityl=triphenylmethyl, Tf=trifluoromethanesulfonyl, Bn=benzyl, LDBB=lithium ditert-butylbiphenyl, DMAP=4-dimethylaminopyridine, MsCl=methanesulfonyl chloride, LiHMDS=lithium hexamethyldisilazide.
8. D. A. Evans, E. Vogel, J. V. Nelson, J. Am Chem. Soc. 1979, 101, 6120-6123.
9. Reaction of the E boron enolate derived from 1 with isobutyraldehyde gave low stereoinduction (2:1).
10. High levels of 1,2-diastereoselection in the addition of various nucleophiles to α-methyl-β-methylene substrates are precedented: a) F. Sato, Y. Takeda, H. Uchiyama, Y. Kobayashi, J. Chem Soc. Chem. Commun. 1984, 1132-1134; b) F. Sato, M. Kusakabe, Y. Kobayashi, ibid. 1984, 1130-1131; c) F. Sato, M. Kusakabe, T. Kato, Y. Kobayashi, ibid. 1984, 1331-1332.
11. High levels of 1,2-diastereoselection in the addition of various nucleophiles to α-methyl-β-methylene substrates are precedented: a) F. Sato, Y. Takeda, H. Uchiyama, Y. Kobayashi, J. Chem Soc. Chem. Commun. 1984, 1132-1134; b) F. Sato, M. Kusakabe, Y. Kobayashi, ibid. 1984, 1130-1131; c) F. Sato, M. Kusakabe, T. Kato, Y. Kobayashi, ibid. 1984, 1331-1332.
12. High levels of 1,2-diastereoselection in the addition of various nucleophiles to α-methyl-β-methylene substrates are precedented: a) F. Sato, Y. Takeda, H. Uchiyama, Y. Kobayashi, J. Chem Soc. Chem. Commun. 1984, 1132-1134; b) F. Sato, M. Kusakabe, Y. Kobayashi, ibid. 1984, 1130-1131; c) F. Sato, M. Kusakabe, T. Kato, Y. Kobayashi, ibid. 1984, 1331-1332.
13. a) D. A. Evans, J. L. Duffy, M. J. Dart, unpublished results; b) D. A. Evans, J. V. Nelson, T. Taber, in Topics in Stereochem. 1982, 13, pp. 1-115; c) W. R. Roush, J. Org. Chem. 1991, 56, 4151-4157.
14. a) D. A. Evans, J. L. Duffy, M. J. Dart, unpublished results; b) D. A. Evans, J. V. Nelson, T. Taber, in Topics in Stereochem. 1982, 13, pp. 1-115; c) W. R. Roush, J. Org. Chem. 1991, 56, 4151-4157.
15. a) D. A. Evans, J. L. Duffy, M. J. Dart, unpublished results; b) D. A. Evans, J. V. Nelson, T. Taber, in Topics in Stereochem. 1982, 13, pp. 1-115; c) W. R. Roush, J. Org. Chem. 1991, 56, 4151-4157.
16. K. Ganesan, H. C. Brown, J. Org. Chem. 1993, 58, 7162-7169.
17. Aldehyde 2 was used directly in these experiments without purification. Exposure of 2 to silica gel led to isomerization to the α,β-unsaturated aldehyde.
18. 5) was recovered (15%).
19. 2AlCl see H. Köster, N. D. Sinha, Tetrahedron Lett. 1982, 23, 2641-2644.
20. The use of aqueous Rochelle's salt in the isolation was essential for removing the organoaluminum salts prior to concentration; otherwise, residual aluminum-promoted spiroketal isomerization to the undesired diaxial anomer took place.
21. Unchanged aldehyde 5 (11%) was also recovered in diastereomerically pure form.
22. The moderate yield for this transformation may be partly due to difficulties in isolating the polar acid triol on small scale. TLC analysis of the reaction suggests a clean and selective transformation.
23. J. Inanaga, K. Hirata, H. Saeki, T. Katsuki, M. Yamaguchi, Bull. Chem. Soc. Jpn. 1979, 52, 1989-1993.
24. 1 TES ester, which is cleaved during purification on silica gel.
25. We thank Professor G. R. Pettit for providing a natural sample of spongistatin 2.
26. We thank Professor M. Kobayashi for providing copies of spectra of natural altohyrtin C.
27. While addition of the side chain at an even later stage may be possible, preliminary investigations of an alternative route involving lactonization of the dihydropyran seco acid corresponding to 9 and subsequent side-chain addition suggest that the epoxidation/allylstannane addition sequence may be more difficult.