Macho Total Synthesis

Robert F. Service (News Focus, 9 July, p. [184][1]) has written an insightful critique of what insiders call “macho total synthesis,” in which huge teams (20 to 30 postdocs and graduate students representing a critical mass) race to be the first to accomplish the synthesis of extremely complex natural products. In his list of superstars, Service does not mention one, who not only is a striking exception—hardly ever publishing a paper with more than a couple of collaborators—but also one who has trained at least three of the “superstars” listed by Service: Gilbert Stork of Columbia University, whose accomplishments over the course of five decades have won him every major award except the Nobel Prize. But there is an interesting cultural point that to my knowledge has also never been raised. Women now represent 30 to 40% of the graduate student pool in most chemistry departments of major American research universities, and just about every branch of chemistry but one can now boast of some distinguished female tenured professors. The striking exception is “organic total synthesis.” Even worse, I know of no serious total synthesis team that has more than a couple of female members. Any practitioner of this testosterone-drenched sub-branch of chemistry should consider what practices deter talented women from even entering such academic laboratories, let alone leading them. I could provide a list of such practices, but I believe that it would be more persuasive if women cited them. Service concludes that making natural products and their kin in large quantities so biologists can study their effects should be one of the justifications for pursuing such macho syntheses. Worthy as such an aim might be, it seems to me unrealistic; nor do I believe that it applies to any of the 10 examples listed in Service's table of “total synthesis highlights.” That should not be surprising, because practitioners in the field cannot afford the effort—in terms of financial resources, manpower, and time—to repeat such multi-step syntheses on the required scale. In fact, what possible incentives could be offered to new graduate students or postdocs to repeat over and over again synthetic sequences that their predecessors had already published? # "Macho Total Synthesis" {#article-title-2} ![Figure][2] The structure of polytoxin (top), a compound from Palythoa vestitis, a soft coral (bottom) CREDITS: PHOTO: L.S. ROBERTS/VISUALS UNLIMITED/SOURCE: NICOLAOU ET AL., JOURNAL OF CHEMICAL EDUCATION, 75 , NO. 10 (1998) ![Figure][2] Service's article is a poor catalyst for the debate it attempts to stimulate. For example, I cannot remember reading a paper on total synthesis from which I did not learn something useful. Papers dealing with contemporary “molecular summits” are among the most educational. Also, the most fundamental benefits of apprenticeship in and practice of total synthesis are not mentioned by Service. No other field of organic chemistry provides a richer context for personal scientific growth, both intellectually and technically. And it is largely because of total synthesis that other fields and interfaces of organic chemistry, and the study of basic chemical principles, have recently flourished. I would not trade my training in the competitive environment of total synthesis for any other. I owe my professional spirit and any future successes to this background. Synthesis, with all of its facets, must persevere as a mainstay of the chemical frontier. Chemistry as a whole will always enjoy a steady advance sprinkled with dramatic breakthroughs. For decades, the steady advance has been fueled in good measure by the example and excitement of total synthesis. Dramatic breakthroughs in chemistry will often be made by those schooled in total synthesis. Total “synthetikers” enjoy the advantage of being able to make any molecules we want by simply “taking known reactions and putting them in a new order” (humor intended). We can think deeply about chemistry from broad experience, and so extend our imaginations and productivity to any chemical problem we choose. What other concern can claim this continuing impact? [1]: /lookup/doi/10.1126/science.285.5425.184 [2]: pending:yes