This review is an updated and expanded version of the three prior reviews that were published in this journal in 1997, 2003, and 2007. In the case of all approved therapeutic agents, the time frame has been extended to cover the 30 years from January 1, 1981, to December 31, 2010, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2010 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a “natural product mimic” or “NM” to join the original primary divisions and have added a new designation, “natural product botanical” or “NB”, to cover those botanical “defined mixtures” that have now been recognized as drug entities by the FDA and similar organizations. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 175 small molecules, 131, or 74...

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Natural Products As Sources of New Drugs over the 30 Years from 1981 to 2010

"Chemists familiar with conventional quantum mechanics will applaud and benefit greatly from this particularly instructive, thorough and clearly written exposition of density functional theory: its basis, concepts, terms, implementation, and performance in diverse applications. Users of DFT for structure, energy, and molecular property computations, as well as reaction mechanism studies, are guided to the optimum choices of the most effective methods. Well done!" Paul von RaguE Schleyer "A conspicuous hole in the computational chemist's library is nicely filled by this book, which provides a wide-ranging and pragmatic view of the subject.[...It] should justifiably become the favorite text on the subject for practioneers who aim to use DFT to solve chemical problems." J. F. Stanton, J. Am. Chem. Soc. "The authors' aim is to guide the chemist through basic theoretical and related technical aspects of DFT at an easy-to-understand theoretical level. They succeed admirably." P. C. H. Mitchell, Appl. Organomet. Chem. "The authors have done an excellent service to the chemical community. [...] A Chemist's Guide to Density Functional Theory is exactly what the title suggests. It should be an invaluable source of insight and knowledge for many chemists using DFT approaches to solve chemical problems." M. Kaupp, Angew. Chem.

A Chemist's Guide to Density Functional Theory

1. Advantages of Chemical Redox Agents 878 2. Disadvantages of Chemical Redox Agents 879 C. Potentials in Nonaqueous Solvents 879 D. Reversible vs Irreversible ET Reagents 879 E. Categorization of Reagent Strength 881 II. Oxidants 881 A. Inorganic 881 1. Metal and Metal Complex Oxidants 881 2. Main Group Oxidants 887 B. Organic 891 1. Radical Cations 891 2. Carbocations 893 3. Cyanocarbons and Related Electron-Rich Compounds 894

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Chemical Redox Agents for Organometallic Chemistry

Catalytic dehydrogenative cross-coupling: forming carbon-carbon bonds by oxidizing two carbon-hydrogen bonds

The widespread use of controlled molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular systems, which by and large rely upon electronic and chemical effects to carry out their functions, and the machines of the macroscopic world, which utilize the synchronized movements of smaller parts to perform specific tasks. This is a scientific area of great contemporary interest and extraordinary recent growth, yet the notion of molecular-level machines dates back to a time when the ideas surrounding the statistical nature of matter and the laws of thermodynamics were first being formulated. Here we outline the exciting successes in taming molecular-level movement thus far, the underlying principles that all experimental designs must follow, and the early progress made towards utilizing synthetic molecular structures to perform tasks using mechanical motion. We also highlight some of the issues and challenges that still need to be overcome.

Synthetic molecular motors and mechanical machines.

5. Stereoselective Intermolecular Addhion Reactions to Double Bonds Controlled by Allylic 1,bStrain 5.1. Hydrogenation 5.2. Hydroboration 5.3. Epoxldation and Cycbpropanation 8. Diastereoselecthre Enolate Alkylations Controlled by Allyllc 1.3-Strain 7. Chirality Transfer in Reactions of Allylsilanes and Allylboronates 8. Nucleophilic AddRion to Double Bonds Controlled by Allylic 1.3-Strain 9. Reactions of Benzylic Systems Controlled by Allylic 1,3-Strain 10. Allylic 1 ,bStrain Control of Dlastereoselecthre Reactions InvoMng Heteroallyl Systems 10.1. 2-Azaallyl Systems 10.2. 2-Oxonlaallyl Systems 10.3. Ntrones 10.4. Other Azaallyllc Systems 10.5. Vinyl Sulfoxides 11. Conformational Control around Bonds to Three-Membered Rings Related to Allylic 1.3-Strain 12. Epilogue

Allylic 1,3-strain as a controlling factor in stereoselective transformations

In this tutorial review the economies of synthesis are analysed from both detailed and macroscopic perspectives, using case-studies from complex molecule synthesis. Atom, step, and redox economy are more than philosophical constructs, but rather guidelines, which enable the synthetic chemist to design and execute an efficient synthesis. Students entering the field of synthesis might find this tutorial helpful for understanding the subtle differences between these economic principles and also see real-world situations where such principles are put into practice.

The economies of synthesis

In an ideal synthesis, the formation of the CC bonds as well as the creation of the chiral centers and of the final functionality would be carried out simultaneously in each step. Accordingly, stereoselective CC bond forming reactions are required. Instead of a pair of diastereomers, a synthesis should yield only one of the two possible diastereomers. Such selectivity is often achieved in the addition of crotylboron, -aluminum, -tin, -titanium, and -chromium compounds to aldehydes. Depending on whether one starts from E- or Z-crotyl compounds, one diastereomeric adduct is formed preferentially. In this case the newly formed CC bond carries a methyl substituent. However, the synthetic goal is often a compound carrying an oxygen function at the site of the new CC bond. Compounds of this type can be obtained through addition of heteroatom-substituted allylboronic acid esters or analogous reagents to aldehydes.

Diastereogenic Addition of Crotylmetal Compounds to Aldehydes

The introduction and removal of protecting groups are steps that unnecessarily increase the length of multistep syntheses. Hence, efficient syntheses are those that avoid the use of protecting groups. Protecting-group-free syntheses are highlighted in this review, in order to illustrate strategies by which the use of protecting groups can be minimized.

Protecting-group-free synthesis

Stereoselective Syntheses of Building Blocks with Three Consecutive Stereogenic Centers: Important Precursors of Polyketide Natural Products [New Synthetic Methods (68)]

Reinhard W. Hoffmann

Papers

Allylic 1,3-strain as a controlling factor in stereoselective transformations

The economies of synthesis

Diastereogenic Addition of Crotylmetal Compounds to Aldehydes

Protecting-group-free synthesis

Stereoselective Syntheses of Building Blocks with Three Consecutive Stereogenic Centers: Important Precursors of Polyketide Natural Products [New Synthetic Methods (68)]