https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

Although fire is now rarely used in synthetic chemistry, it was not until Robert Bunsen invented the burner in 1855 that the energy from this heat source could be applied to a reaction vessel in a focused manner. The Bunsen burner was later superseded by the isomantle, oil bath, or hot plate as a source for applying heat to a chemical reaction. In the past few years, heating and driving chemical reactions by microwave energy has been an increasingly popular theme in the scientific community. This nonclassical heating technique is slowly moving from a laboratory curiosity to an established technique that is heavily used in both academia and industry. The efficiency of "microwave flash heating" in dramatically reducing reaction times (from days and hours to minutes and seconds) is just one of the many advantages. This Review highlights recent applications of controlled microwave heating in modern organic synthesis, and discusses some of the underlying phenomena and issues involved.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.200400655

Controlled microwave heating in modern organic synthesis.

In studying the evolution of organic chemistry and grasping its essence, one comes quickly to the conclusion that no other type of reaction plays as large a role in shaping this domain of science than carbon-carbon bond-forming reactions. The Grignard, Diels-Alder, and Wittig reactions are but three prominent examples of such processes, and are among those which have undeniably exercised decisive roles in the last century in the emergence of chemical synthesis as we know it today. In the last quarter of the 20th century, a new family of carbon-carbon bond-forming reactions based on transition-metal catalysts evolved as powerful tools in synthesis. Among them, the palladium-catalyzed cross-coupling reactions are the most prominent. In this Review, highlights of a number of selected syntheses are discussed. The examples chosen demonstrate the enormous power of these processes in the art of total synthesis and underscore their future potential in chemical synthesis.

Palladium-catalyzed cross-coupling reactions in total synthesis.

6.4. Polyynes 3123 6.5. Using R-Hydroxy Stannanes 3124 6.6. Using the Hurtley Reaction 3124 6.7. Using a Methylenation Reaction 3125 7. Conclusions and Future Prospects 3125 8. Uncommon Abbreviations 3125 9. Acknowledgments 3125 10. Note Added in Proof 3125 11. References 3126 * Authorstowhomcorrespondenceshouldbeaddressed(evano@chimie.uvsq.fr, nicolas.blanchard@uha.fr). † Université de Versailles Saint Quentin en Yvelines. ‡ Université de Haute-Alsace. Chem. Rev. 2008, 108, 3054–3131 3054

Copper-mediated coupling reactions and their applications in natural products and designed biomolecules synthesis.

Practical methodologies for the synthesis of indoles.

Chemistry and Biology of the Enediyne Anticancer Antibiotics

One can view plants as a reference library of compounds waiting to be searched by a chemist who is looking for a particular property. Taxol, a complex polyoxygenated diterpene isolated from the Pacific Yew, Taxus brevifolia, was discovered during extensive screening of plant materials for antineoplastic agents during the late 1960s. Over the last two decades, interest in and research related to taxol has slowly grown to the point that the popular press now seems poised to scoop each new development. What was once an obscure compound, of interest only to the most masochistic of synthetic chemists and an equally small number of cellular biologists, has become one of the few organic compounds, which, like benzene and aspirin, is recognizable by name to the average citizen. In parallel, the scientific study of taxol has blossomed. Physicians are currently studying its effects on nearly every known neoplasm. Biologists are using taxol to study the mechanisms of cell function by observing the effects of its interactions with the cellular skeletal systems. Synthetic chemists, absorbed by the molecule's unique and sensitive structure and functionality, are exploring seemingly every available pathway for its synthesis. Indeed, the demand for taxol has risen so in the last five years that alternative sources to the extraction of T. brevifolia are being vigorously pursued. Because of the rapidly expanding scope of research in the multifaceted study of taxol, those who are interested in the field may find acquisition of a reasonable base of knowledge an arduous task. For this reason, this account attempts to bring together, for the first time, in a cogent overview the chemistry and biology of this unique molecule.

Chemistry and Biology of Taxol

The rational design and biological actions of a new class of DNA-cleaving molecules with potent and selective anticancer activity are reported. These relatively simple enediyne-type compounds were designed from basic chemical principles to mimic the actions of the rather complex naturally occurring enediyne anticancer antibiotics, particularly dynemicin A. Equipped with locking and triggering devices, these compounds damage DNA in vitro and in vivo on activation by chemical or biological means. Their damaging effects are manifested in potent anticancer activity with remarkable selectivities. Their mechanism of action involves intracellular unlocking and triggering of a Bergman reaction, leading to highly reactive benzenoid diradicals that cause severe DNA damage. The results of these studies demonstrate the potential of these de novo designed molecules as biotechnology tools and anticancer agents.

https://science.sciencemag.org/content/sci/256/5060/1172.full.pdf

Designed enediynes: a new class of DNA-cleaving molecules with potent and selective anticancer activity.

Chemie und Biologie von Endiin-Cytostatica/Antibiotica

Following the discovery of the enediyne anticancer antibiotics, investigations were initiated directed toward the design, synthesis, and study of simple monocyclic conjugated enediynes. In this article the synthesis of the parent 10-membered ring enediyne found in the enediyne natural products and its properties are described. In addition to the parent hydrocarbon 27, the synthetic methodology developed based on the Ramberg-Blcklund reaction delivers a series of higher ring homologs (17-22) and the water soluble version of the 10-membered ring compound 47. Molecular mechanics calculations on these systems led to a number of geometrical parameters which correlated well with their tendencies to undergo the Bergman cycloaromatization reaction. Kinetic studies on the Bergman cycloaromatization of the 10-membered ring enediynes 27 and 47 led to the following thermodynamic values: 27, energy of activation (E,) = 23.8 kcal/mol, AG* (37 "C) = 24.6 kcal/mol; 47, energy of activation (E,) = 31.5 kcal/mol, AG' (37 "C) = 24.8 kcal/mol. The designed enediyne 47 showed potent DNA-cleaving properties becoming the first synthetic molecule to mimic the action of the naturally occurring enediynes in this regard.

Wei-Min Dai

Papers

Chemistry and Biology of the Enediyne Anticancer Antibiotics

Chemistry and Biology of Taxol

Designed enediynes: a new class of DNA-cleaving molecules with potent and selective anticancer activity.

Chemie und Biologie von Endiin-Cytostatica/Antibiotica

Design, synthesis, and study of simple monocyclic conjugated enediynes. The 10-membered ring enediyne moiety of the enediyne anticancer antibiotics