A solid-supported, enantioselective synthesis suitable for the rapid preparation of large numbers of diverse structural analogues of (-)-saframycin A

Journal of the American Chemical Society

Volumn 124, Issue 44, 2002, Pages 12969-12971

  Myers, Andrew G ^a   Lanman, Brian A ^a  

^a HARVARD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

SAFRAMYCIN A;

ADAPTATION; ANALYTIC METHOD; ARTICLE; DERIVATIZATION; ENANTIOMER; PROTEIN ASSEMBLY; SOLID TUMOR; STRUCTURE ANALYSIS; SYNTHESIS; TRANSCRIPTION REGULATION;

ALKALOIDS; ANTIBIOTICS, ANTINEOPLASTIC; CHEMISTRY, ORGANIC; ISOQUINOLINES; STEREOISOMERISM;

EID: 0037032215     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja027729n     Document Type: Article

References (23)

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6. (a) Plowright, A. T.; Schaus, S. E.; Myers, A. G. Chem. Biol. 2002, 9, 607-618. Transcriptional profiles of Et-743 and the more potent synthetic analogue phthalascidin in two human cancer cell lines were likewise found to be nearly identical: (b) Martinez, E. J.; Corey, E. J.; Owa, T. Chem. Biol. 2001, 8, 1151-1160.
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17. This is presumably a consequence of the introduction of the "remote" stereocenter at C-2 of the morpholine nucleus, rather than an idiosyncrasy of solid-versus solution-phase chemistry, but this has not yet been established experimentally.
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19. Unreacted silyl chloride sites on the resin were capped with methanol. Yields in solid-phase transformations were determined spectrophotometrically from the UV absorption of dibenzofulvene released upon treatment with 20% piperidine-DMF and were confirmed in several cases by product isolation following acid-catalyzed cleavage of the silyl ether-linked intermediates.
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22. We have previously shown that the pentacyclic intermediate 11 can be converted into saframycin A in 52% yield (3 steps, see ref 5).
23. 1H NMR analysis, with two exceptions: products 20 and 21 were ∼80% pure, containing impurities from self-condensation of phenylacetaldehyde.