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Bryostatin Synthesis

January 26, 2009 | A version of this story appeared in Volume 87, Issue 4

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THE ARTICLE "Bryostatin, Faster" (C&EN, Dec. 1, 2008, page 11) comments in deservedly complimentary terms on the recent article in Nature (2008, 456, 485) dealing with the total synthesis of bryostatin by Barry M. Trost and Guangbin Dong of Stanford University. But who isolated the bryostatins? Who established their structures? Who initially pursued their anticancer activity? Without these achievements, the synthesis would simply constitute chemical acrobatics that never would have been accepted by Nature.

These decade-long efforts by G. R. Pettit's group at Arizona State University are concealed by reference to a generic review article authored by others. There are a couple of "et al." references that also mask Pettit's name. This demeaning treatment of the key work of earlier investigators in the field of natural products by chemists who then undertake the total synthesis of the molecule in question is unfortunately all too common—either because of sloppiness or as a discreet attempt to eliminate any reference to the initial discoverers.

Trost's treatment of Pettit is particularly egregious given the well-known fact in the chemical community that the spectacularly laborious decade-long efforts of one of the heroes of marine natural products chemistry—the person who personally collected the bryozoan, isolated the bryostatins, established their constitution, and pursued their anticancer activity against all odds—were terminated through a draconian closure of his laboratory by the new administrators of Arizona State University. This was also covered in C&EN (Feb. 6, 2006, page 10) as well as in Nature (2007, 447, 968 and 1052; 2007, 448, 533).

Trost had no problem in starting his bibliography through references to his own work in 1991 and 1983 rather than to some anonymous review article. I believe it is time for editors to require that proper citation of the original literature by the original authors take precedence over dropping them into the black hole of third-person reviews. I raise this question as a matter of professional ethics rather than referring to the impact of such actions on citation analysis. How would Trost and Dong feel—once next year's reviews on total syntheses in organic chemistry have appeared—to find their bryostatin synthesis buried in such a third-person review?

Carl Djerassi
Stanford, Calif.



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