Editorial pubs.acs.org/CR
Introduction: Natural Product Synthesis
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manuscript and presents the use of multistep synthesis to access clinical candidates based on natural product-based structures.7 Like the Boger contribution, the complexity of the structures that are accessible (and here the discussion is limited to those that are in clinical development) supports the position that natural products synthesis, perhaps now more than ever, is equipped to address major issues in human health. Finally the contribution by Johnson and Siegel highlights new applications of natural products to modulate stem cell fate, which have broad biomedical applications.8 We note that the timing of this issue coincides with the 100th anniversary of the birth of Robert Burns Woodward, who was, of course, an enormous inspiration to the field of natural products chemistry. It is interesting to consider what Woodward’s reaction to this thematic issue might have been. Undoubtedly, he would be surprised by the standardized chemical structures, and someone would have had to explain ChemDraw to him (but he would certainly have caught on quickly). We believe that he would be immensely impressed by the distance that the field has traveled and the impacts that it now has on allied areas of research, and that he would, like all of us, look forward with great excitement to what lies ahead. We believe the review articles in this issue beautifully capture these aspirational aspects of the field. We would like to extend our sincere gratitude to the authors for their time in preparing the contributions in this issue, to the ACS staff and editors for handling the submissions, and to the reviewers whose insightful evaluations helped to hone and refine the final manuscripts.
e are very pleased to introduce this thematic issue of Chemical Reviews and are thrilled by the quality and scope of the manuscripts prepared by the contributing authors. The contents of the issue focus on advances in natural products chemistry at the methodological, strategic, and applied levels, and they make it clear that the reach of the field continues to expand with a richness, insight, and level of rigor rarely emulated in other fields. These qualities ensure the continued vibrancy of natural product synthesis for generations to come. Natural products continue to drive researchers deeper into basic chemistry. As elegantly outlined by Ebner and Carreira,1 the construction of seemingly simple cyclopropanes en route to complex structures still presents immense challenges and continues to motivate the development of powerful new synthetic methods of broad utility, and the strained rings themselves provide significant strategic opportunities. The breathtaking advances in second- and third-row transition metal-mediated reactions that have moved the field forward have allowed a shift in the focus of reaction development to benign, inexpensive first-row transition metals. As discussed by Zweig, Kim, and Newhouse in their particularly comprehensive review,2 we now have at our disposal a large suite of powerful first row metal-mediated transformations and these methods are having a substantial impact on ways in which complex molecules are disconnected and prepared. The chiral pool is perhaps one of the oldest and most reliable methods to synthesize natural products in enantioenriched form. Brill, Condakes, Ting, and Maimone discuss innovative (and, in most cases, entirely nonobvious) applications of chiral terpene building blocks toward the synthesis of more complex terpene natural products.3 Most if not all of the syntheses described in this issue were carried out in traditional “batch” format. The “User’s Guide” to flow chemistry presented by Plutschack, Pieber, Gilmore, and Seeberger is certain to motivate and enable practitioners of the field to apply these modern advances in complex multistep sequences.4 Flow presents several advantages including safety, scalability, and reproducibility, as well as economic benefits, and we expect the community will ultimately benefit immensely from these technologies. The contribution of Shugrue and Miller addresses one of the most challenging (and enduring) issues facing the field: the manipulation of one functional group in the presence of multiple competitive reacting loci with surgical precision.5 Here, advances in this area in the settings presented by polyfunctional natural products are comprehensively reviewed. Natural products chemistry will continue to play a critical role in efforts to solve the problem posed by antibiotic resistance. In that vein, Okano, Isley, and Boger outline recent breathtaking advances in the synthesis and modification of glycopeptide antibiotics,6 which are essential medicines used to treat lifethreatening bacterial infections. The scope and magnitude of the modifications that are possible, and the structures that can be prepared in a fully synthetic fashion, underscore the heights to which the field has climbed. The contribution of Allred, Manoni, and Harran goes hand-in-hand with the Boger © 2017 American Chemical Society
Seth B. Herzon* Yale University
Christopher D. Vanderwal* University of California, Irvine
AUTHOR INFORMATION Corresponding Authors
*E-mail:
[email protected]. *E-mail:
[email protected]. ORCID
Seth B. Herzon: 0000-0001-5940-9853 Christopher D. Vanderwal: 0000-0001-7218-4521 Notes
Views expressed in this editorial are those of the authors and not necessarily the views of the ACS. Special Issue: Natural Product Synthesis Published: September 27, 2017 11649
DOI: 10.1021/acs.chemrev.7b00520 Chem. Rev. 2017, 117, 11649−11650
Chemical Reviews
Editorial
Biographies
(2) Zweig, J. E.; Kim, D. E.; Newhouse, T. R. Methods Utilizing First-Row Transition Metals in Natural Product Total Synthesis. Chem. Rev. 2017, DOI: 10.1021/acs.chemrev.6b00833. (3) Brill, Z. G.; Condakes, M. L.; Ting, C. P.; Maimone, T. J. Navigating the Chiral Pool in the Total Synthesis of Complex Terpene Natural Products. Chem. Rev. 2017, DOI: 10.1021/acs.chemrev.6b00834. (4) Plutschack, M. B.; Pieber, B.; Gilmore, K.; Seeberger, P. H. The Hitchhiker’s Guide to Flow Chemistry. Chem. Rev. 2017, DOI: 10.1021/acs.chemrev.7b00183. (5) Shugrue, C. R.; Miller, S. J. Applications of Nonenzymatic Catalysts to the Alteration of Natural Products. Chem. Rev. 2017, DOI: 10.1021/acs.chemrev.7b00022. (6) Okano, A.; Isley, N. A.; Boger, D. L. Total Synthesis of Vancomycin-Related Glycopeptide Antibiotics and Key Analogues. Chem. Rev. 2017, DOI: 10.1021/acs.chemrev.6b00820. (7) Allred, T. K.; Manoni, F.; Harran, P. G. Exploring the Boundaries of “Practical”: De Novo Syntheses of Complex Natural Product-Based Drug Candidates. Chem. Rev. 2017, DOI: 10.1021/acs.chemrev.7b00126. (8) Johnson, T. C.; Siegel, D. Directing Stem Cell Fate: The Synthetic Natural Product Connection. Chem. Rev. 2017, DOI: 10.1021/acs.chemrev.7b00015.
Seth Herzon completed his undergraduate studies at Temple University in 2002 and obtained a Ph.D. from Harvard University in 2006, where he worked under the guidance of Professor Andrew G. Myers. His graduate studies focused on the synthesis of the antiproliferative alkaloids avrainvillamide and stephacidin B. He was an NIH postdoctoral fellow in the laboratory of Professor John F. Hartwig at the University of Illinois, Urbana−Champaign, from 2006− 2008. In the Hartwig laboratory he developed new metal-catalyzed C− H functionalization reactions and new methods for high-throughput reaction discovery. In 2008 he began his independent career at Yale. He was promoted to Associate Professor in 2012 and Full Professor in 2013. As of 2015 he also holds a joint appointment as Professor of Pharmacology at the Yale School of Medicine. He is also a member of the Yale Comprehensive Cancer Center and the Developmental Therapeutics Program.
Christopher Vanderwal received a B.Sc. degree in Biochemistry (1995) and an M.Sc. degree in Chemistry (1998) from the University of Ottawa. He then moved to the Scripps Research Institute for doctoral studies in the group of Professor Erik Sorensen. After obtaining his Ph.D. in 2003, Chris joined the group of Professor Eric Jacobsen at Harvard University as a Jane Coffin Childs postdoctoral associate. In 2005, Chris began his independent academic career at the University of California, Irvine, where he is currently Professor of Chemistry. His research group develops strategies for the streamlined syntheses of complex bioactive natural products.
REFERENCES (1) Ebner, C.; Carreira, E. M. Cyclopropanation Strategies in Recent Total Syntheses. Chem. Rev. 2017, DOI: 10.1021/acs.chemrev.6b00798. 11650
DOI: 10.1021/acs.chemrev.7b00520 Chem. Rev. 2017, 117, 11649−11650
