Multigram Synthesis of the C29-C51 Subunit and Completion of the Total Synthesis of Altohyrtin C (Spongistatin 2)

Journal of the American Chemical Society

Volumn 125, Issue 42, 2003, Pages 12844-12849

  Heathcock, Clayton H ^a   McLaughlin, Mark ^a   Medina, Jesus ^a   Hubbs, Jed L ^a   Wallace, Grier A ^a   Scott, Robert ^a   Claffey, Michele M ^a   Hayes, Christopher J ^a   Ott, Gregory R ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NATURAL PRODUCTS;

BORON COMPOUNDS; OXIDATION; REDUCTION; STEREOCHEMISTRY; SYNTHESIS (CHEMICAL);

ALDEHYDES;

ACETONE; ALDEHYDE; BORON; PHOSPHONIUM DERIVATIVE; SPONGISTATIN 2;

ALDOL REACTION; ARTICLE; CATALYSIS; CYCLIZATION; DEPROTECTION REACTION; DESS MARTIN OXIDATION; DIASTEREOISOMER; PROTON NUCLEAR MAGNETIC RESONANCE; REDUCTION; SYNTHESIS;

ALDEHYDES; ANTINEOPLASTIC AGENTS; DEOXYGLUCOSE; EPOXY COMPOUNDS; MACROLIDES; MALATES; PROPANOLS;

EID: 0142104229     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja030317+     Document Type: Article

References (25)

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2. A comprehensive reference list for previous synthetic work, presented in ref 1, is omitted here in the interest of conserving journal space.
3. For our first-generation synthesis of a C29-C44 fragment, see: Wallace, G. A.; Scott, R. W.; Heathcock, C. H. J. Org. Chem. 2000, 65, 4145.
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8. Although this sequence begins and ends with a triethylsilyl protecting group on the primary hydroxyl, an intermediate pivaloyl group was necessary because the acidic conditions of the bromoboration reaction were not compatible with the silyl ether.
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16. Ott, G. R.; Heathcock, C, H. unpublished results. These model studies were carried out on the substrate reported in: Ott, G. R.; Heathcock, C. H. Org. Lett. 1999, 1, 1475.
17. Ott, G. R.; Heathcock, C, H. unpublished results. These model studies were carried out on the substrate reported in: Ott, G. R.; Heathcock, C. H. Org. Lett. 1999, 1, 1475.
18. Paterson, I.; Cowden, C. J.; Rahn, V. S.; Woodrow, M. D. Synlett 1998, 915. In contrast, a similar deprotection of a bis-PMB ether was achieved without difficulty in the syntheses of altohyrtin A by Kishi (ref 13) and by Paterson (Paterson, I.; Chen, D. Y.-K.; Coster, M. J.; Aceña, J. L.; Bach, J.; Gibson, K. R.; Keown, L. E.; Oballa, R. M.; Trieselmann, T.; Wallace, D. J.; Hodgson, A. P.; Norcross, R. D. Angew. Chem., Int. Ed. 2001, 40, 4055-4060). It appears that the presence of the side-chain halogen retards the oxidation process that we had observed, permitting conventional removal of the PMB groups.
19. Paterson, I.; Cowden, C. J.; Rahn, V. S.; Woodrow, M. D. Synlett 1998, 915. In contrast, a similar deprotection of a bis-PMB ether was achieved without difficulty in the syntheses of altohyrtin A by Kishi (ref 13) and by Paterson (Paterson, I.; Chen, D. Y.-K.; Coster, M. J.; Aceña, J. L.; Bach, J.; Gibson, K. R.; Keown, L. E.; Oballa, R. M.; Trieselmann, T.; Wallace, D. J.; Hodgson, A. P.; Norcross, R. D. Angew. Chem., Int. Ed. 2001, 40, 4055-4060). It appears that the presence of the side-chain halogen retards the oxidation process that we had observed, permitting conventional removal of the PMB groups.
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25. -11 in MDA-MB-435 breast cancer). In addition, this analogue has nanomolar GI50 against a number of other cancer lines, including eight nonsmall cell lung cancers, five other colon cancers, four CNS cancers, six other melanomas, six ovarian cancers, seven renal cancers, and two other breast cancers. Edward Sausville, National Cancer Institute, private communication, August 14, 2003.