The total synthesis of optically pure (9R,13S)- and (9R,13R)-7-deoxy-13-dihydrodaunomycinone
| dc.contributor.author | Russell, R.A. | |
| dc.contributor.author | Irvine, R.W. | |
| dc.contributor.author | Warrener, R.N. | |
| dc.date.issued | 1986 | |
| dc.description.abstract | 13-Dihydrodaunomycin 1 has long been recognized as the major human metabolite of the antineoplastic anthracycline daunomycin 2.<sup>1</sup> Whilst 1 has been prepared by microbial<sup>2</sup> and chemical reduction<sup>3</sup>of 2, no attempt to assign the stereochemistry at C13<sup>4</sup> has been reported. Recently Cassinelli et al. have reported<sup>5</sup>that 4-demeth-oxydaunomycin 3 (idarubicin) can be reduced microbially to afford an idarubicinol 4 identical with that excreted by patients treated with 3. These authors initially assigned the 13R stereochemistry to this product, although this was subsequently corrected by Broadhurst et al.,<sup>6</sup> who showed that the totally synthetic 13S isomer corresponded to the biologically obtained product. As both dihydroderivatives 1 and 4 are active antineoplastic agents,<sup>2</sup><sup>,7</sup>routes leading to their total synthesis are of considerable interest. In addition another dihydro compound, namely 7-deoxy-13-dihydrodaunomycinone 5, has reportedly been isolated from a strain of Streptomyces (PD.J566) originating from Michaelmas Cay in Australia.<sup>8</sup> Since this product occurred together with known daunomycin derivatives, it was assumed to have the 9R configuration. However, subsequent attempts to synthesize 5 stereospecifically by borohydride reduction of (−)-7-deoxydaunomycinone yielded unseparated mixtures of the9R,13R and 9R,13S isomers.<sup>9</sup> Consequently, the configuration of C13 of the natural product remained undefined. © 1986, American Chemical Society. All rights reserved. | |
| dc.description.statementofresponsibility | Richard A. Russell, Robert W. Irvine, Ronald N. Warrener | |
| dc.identifier.citation | Journal of Organic Chemistry, 1986; 51(9):1595-1599 | |
| dc.identifier.doi | 10.1021/jo00359a041 | |
| dc.identifier.issn | 0022-3263 | |
| dc.identifier.issn | 1520-6904 | |
| dc.identifier.uri | http://hdl.handle.net/2440/86661 | |
| dc.language.iso | en | |
| dc.publisher | American Chemical Society | |
| dc.rights | © 1986 American Chemical Society | |
| dc.source.uri | https://doi.org/10.1021/jo00359a041 | |
| dc.title | The total synthesis of optically pure (9R,13S)- and (9R,13R)-7-deoxy-13-dihydrodaunomycinone | |
| dc.type | Journal article | |
| pubs.publication-status | Published |