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

Marine natural products.

/pdf/aryl-aryl-bond-formation-one-century-after-the-discovery-of-1jdyxlkwix.pdf

Aryl-aryl bond formation one century after the discovery of the Ullmann reaction.

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.

Applications in Theranostics Guanying Chen,*,†,‡ Hailong Qiu,†,‡ Paras N. Prasad,*,‡,§ and Xiaoyuan Chen* †School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China ‡Department of Chemistry and the Institute for Lasers, Photonics, and Biophotonics, University at Buffalo, State University of New York, Buffalo, New York 14260, United States Department of Chemistry, Korea University, Seoul 136-701, Korea Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892-2281, United States

Upconversion Nanoparticles: Design, Nanochemistry, and Applications in Theranostics

The design and implementation of cascade reactions is a challenging facet of organic chemistry, yet one that can impart striking novelty, elegance, and efficiency to synthetic strategies. The application of cascade reactions to natural products synthesis represents a particularly demanding task, but the results can be both stunning and instructive. This Review highlights selected examples of cascade reactions in total synthesis, with particular emphasis on recent applications therein. The examples discussed herein illustrate the power of these processes in the construction of complex molecules and underscore their future potential in chemical synthesis.

Cascade reactions in total synthesis.

This protocol details the most commonly used nuclear magnetic resonance (NMR)-based method for deducing the configuration of otherwise unknown stereogenic, secondary carbinol (alcohol) centers (R1R2CHOH (or the analogous amines where OH is replaced by NH2)). This 'Mosher ester analysis' relies on the fact that the protons in diastereomeric alpha-methoxy-alpha-trifluoromethylphenylacetic acid (MTPA) esters (i.e., those derived from conjugation of the carbinol under interrogation with MTPA) display different arrays of chemical shifts (deltas) in their 1H NMR spectra. The protocol consists of the following: (i) preparation of each of the diastereomeric S- and R-MTPA esters and (ii) comparative (Delta delta(SR)) analysis of the 1H NMR spectral data of these two esters. By analyzing the sign of the difference in chemical shifts for a number of analogous pairs of protons (the set of Delta delta(SR) values) in the diastereomeric esters (or amides), the absolute configuration of the original carbinol (or amino) stereocenter can be reliably deduced. A typical Mosher ester analysis requires approximately 4-6 h of active effort over a 1- to 2-d period.

https://www.nature.com/articles/nprot.2007.354.pdf?proof=t

Mosher ester analysis for the determination of absolute configuration of stereogenic (chiral) carbinol carbons

Arynes (aromatic systems containing, formally, a carbon–carbon triple bond) are among the most versatile of all reactive intermediates in organic chemistry. They can be ‘trapped’ to give products that are used as pharmaceuticals, agrochemicals, dyes, polymers and other fine chemicals. Here we explore a strategy that unites the de novo generation of benzynes—through a hexadehydro-Diels–Alder reaction—with their in situ elaboration into structurally complex benzenoid products. In the hexadehydro-Diels–Alder reaction, a 1,3-diyne is engaged in a [4+2] cycloisomerization with a ‘diynophile’ to produce the highly reactive benzyne intermediate. The reaction conditions for this simple, thermal transformation are notable for being free of metals and reagents. The subsequent and highly efficient trapping reactions increase the power of the overall process. Finally, we provide examples of how this de novo benzyne generation approach allows new modes of intrinsic reactivity to be revealed. The de novo generation of benzynes—through a hexadehydro-Diels–Alder reaction—followed by their in situ elaboration is reported; the reaction is metal-free and reagent-free, and reveals new modes of intrinsic benzyne reactivity. Arynes are reactive intermediates derived from aromatic systems, which can be 'trapped' to give products that find use as chemical reagents and in pharmaceuticals, agrochemicals, dyes and polymers. This study explores a new synthetic strategy that combines de novo generation of benzynes — through a hexadehydro-Diels–Alder reaction — with their in situ elaboration into structurally complex benzenoid products. The reaction is metal-free and reagent-free, and the authors provide examples of how this approach allows new modes of intrinsic reactivity to be revealed.

/pdf/the-hexadehydro-diels-alder-reaction-5b7frbdmnq.pdf

The hexadehydro-Diels–Alder reaction

This protocol is intended to provide chemists who discover or make new organic compounds with a valuable tool for validating the structural assignments of those new chemical entities. Experimental ¹H and/or ¹³C NMR spectral data and its proper interpretation for the compound of interest is required as a starting point. The approach involves the following steps: (i) using molecular mechanics calculations (with, e.g., MacroModel) to generate a library of conformers; (ii) using density functional theory (DFT) calculations (with, e.g., Gaussian 09) to determine optimal geometry, free energies and chemical shifts for each conformer; (iii) determining Boltzmann-weighted proton and carbon chemical shifts; and (iv) comparing the computed chemical shifts for two or more candidate structures with experimental data to determine the best fit. For a typical structure assignment of a small organic molecule (e.g., fewer than ∼10 non-H atoms or up to ∼180 a.m.u. and ∼20 conformers), this protocol can be completed in ∼2 h of active effort over a 2-d period; for more complex molecules (e.g., fewer than ∼30 non-H atoms or up to ∼500 a.m.u. and ∼50 conformers), the protocol requires ∼3-6 h of active effort over a 2-week period. To demonstrate the method, we have chosen the analysis of the cis- versus the trans-diastereoisomers of 3-methylcyclohexanol (1-cis versus 1-trans). The protocol is written in a manner that makes the computation of chemical shifts tractable for chemists who may otherwise have only rudimentary computational experience.

/pdf/addendum-a-guide-to-small-molecule-structure-assignment-20o50h20ra.pdf

Addendum: A guide to small-molecule structure assignment through computation of (¹H and ¹³C) NMR chemical shifts.

The sea lamprey is an ancient, parasitic fish that invaded the Great Lakes a century ago, where it triggered the collapse of many fisheries1. Like many fishes, this species relies on chemical cues to mediate key aspects of its life, including migration and reproduction2,3. Here we report the discovery of a multicomponent steroidal pheromone that is released by stream-dwelling larval lamprey and guides adults to spawning streams. We isolated three compounds with pheromonal activity (in submilligram quantities from 8,000 l of larval holding water) and deduced their structures. The most important compound contains an unprecedented 1-(3-aminopropyl)pyrrolidin-2-one subunit and is related to squalamine, an antibiotic produced by sharks4. We verified its structure by chemical synthesis; it attracts adult lamprey at very low (subpicomolar) concentrations. The second component is another new sulfated steroid and the third is petromyzonol sulfate, a known lamprey-specific bile acid derivative. This mixture is the first migratory pheromone identified in a vertebrate and is being investigated for use in lamprey control.

Mixture of new sulfated steroids functions as a migratory pheromone in the sea lamprey

A novel continuous fixed bed reactor process has been developed for the production of biodiesel using a metal oxide-based catalyst. Porous zirconia, titania and alumina micro-particulate heterogeneous catalysts are shown to be capable of continuous rapid esterification and transesterfication reactions under high pressure (ca. 2500 psi) and elevated temperature (300–450 °C). The continuous transesterification of triglycerides and simultaneous esterification of free fatty acids with residence times as low as 5.4 s is described. Biodiesel produced from soybean oil, acidulated soapstock, tall oil, algae oil, and corn oil with different alcohols to make different alkyl esters using this new process pass all current ASTM testing specifications. Furthermore, the economics of this novel process is much more cost competitive due to the use of inexpensive lipid feedstocks that often contain high levels of free fatty acids. The process has been shown to easily scale up a factor of 49 for more than 115 h of continuous operation without loss of conversion efficiency. The increased use of biodiesel world-wide could help reduce the emission of greenhouse gases that are linked to the progression of global warming.

Thomas R. Hoye

Papers

Mosher ester analysis for the determination of absolute configuration of stereogenic (chiral) carbinol carbons

The hexadehydro-Diels–Alder reaction

Addendum: A guide to small-molecule structure assignment through computation of (¹H and ¹³C) NMR chemical shifts.

Mixture of new sulfated steroids functions as a migratory pheromone in the sea lamprey

A continuous catalytic system for biodiesel production