Enantioselective total synthesis of altohyrtin C (spongistatin 2)

Tetrahedron

Volumn 55, Issue 29, 1999, Pages 8671-8726

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

^a HARVARD UNIVERSITY   (United States)

Author keywords

Aldol reactions; Antitumour compounds; Asymmetric synthesis; Marine metabolites

Indexed keywords

SPONGISTATIN 2; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; CONFERENCE PAPER; ENANTIOMER; MARINE ENVIRONMENT; PRIORITY JOURNAL; SYNTHESIS;

EID: 0033575415     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4020(99)00438-X     Document Type: Conference Paper

References (144)

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126. Kishi and coworkers have successfully applied an analogous allyl cuprate addition to an F-ring anomeric epoxide in their synthesis of altohyrtin A: Guo, J. S.; Duffy, K. J.; Stevens, K. L.; Dalko, P. I.; Roth, R. M.; Hayward, M. M.; Kishi, Y. Angew. Chem. Int. Ed. Engl. 1998, 37, 187-192.
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132. We speculate that steric congestion around the reacting center lowers the nucleophilicity of the allylstannane. The consequent failure of the allylslannane addition to compete with nonproductive epoxide decomposition is presumed to be responsible for the lower yields observed for larger allylstannane protecting groups. Results in a similar system (epoxide 69) indicated that TBS (21% yield) and TBDPS (0% yield) protecting groups followed this trend.
133. See reference 65 for experimental details of the reaction in equation 14.
134. Unreacted aldehyde 42 ( 11 %) was also recovered in diastereomerically pure form.
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138. 29 epoxides should not react with methanol, the epoxidation site selectivity can be discerned by mass spectral analysis.
139. Information concerning the stereoselectivity of this epoxidation was not obtained from these small scale experiments. Epoxidation of a simple F ring acetate proceeded with :1 selectivity for the desired isomer. See also: Park, T. K.; Kim, I.J.; Hu, S.; Bilodeau, M. T.; Randolph, J. T.; Kwon, O.; Danishefsky, S. J. J. Am. Chem. Soc. 1996, 118, 11488-11500.
140. 29) was observed if dioxirane stoichiometry was not appropriately controlled.
141. 1 TES ester, which is cleaved during purification on silica gel.
142. Professor G. R. Pettit is gratefully acknowledged for providing a natural sample of spongistatin 2.
143. We thank Professor Motomasa Kobayashi for providing NMR spectra of natural altohyrtin C.
144. This conclusion was subsequently corroborated by Kishi's total synthesis of altohyrtin A/spongistatin 1. See reference 1b.