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

Marine natural products.

Highly dynamic mitotic-spindle microtubules are among the most successful targets for anticancer therapy. Microtubule-targeted drugs, including paclitaxel and Vinca alkaloids, were previously considered to work primarily by increasing or decreasing the cellular microtubule mass. Although these effects might have a role in their chemotherapeutic actions, we now know that at lower concentrations, microtubule-targeted drugs can suppress microtubule dynamics without changing microtubule mass; this action leads to mitotic block and apoptosis. In addition to the expanding array of chemically diverse antimitotic agents, some microtubule-targeted drugs can act as vascular-targeting agents, rapidly depolymerizing microtubules of newly formed vasculature to shut down the blood supply to tumours.

Microtubules as a target for anticancer drugs.

Eating five servings of fruits and vegetables per day! This is what is highly recommended and heavily advertised nowadays to the general public to stay fit and healthy! Drinking green tea on a regular basis, eating chocolate from time to time, as well as savoring a couple of glasses of red wine per day have been claimed to increase life expectancy even further! Why? The answer is in fact still under scientific scrutiny, but a particular class of compounds naturally occurring in fruits and vegetables is considered to be crucial for the expression of such human health benefits: the polyphenols! What are these plant products really? What are their physicochemical properties? How do they express their biological activity? Are they really valuable for disease prevention? Can they be used to develop new pharmaceutical drugs? What recent progress has been made toward their preparation by organic synthesis? This Review gives answers from a chemical perspective, summarizes the state of the art, and highlights the most significant advances in the field of polyphenol research.

Plant Polyphenols: Chemical Properties, Biological Activities, and Synthesis

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.

Starting from the early 1990’s, the chemistry of polyvalent iodine organic compounds has experienced an explosive development. This surging interest in iodine compounds is mainly due to the very useful oxidizing properties of polyvalent organic iodine reagents, combined with their benign environmental character and commercial availability. Iodine(III) and iodine(V) derivatives are now routinely used in organic synthesis as reagents for various selective oxidative transformations of complex organic molecules. Several areas of hypervalent organoiodine chemistry have recently attracted especially active interest and research activity. These areas, in particular, include the synthetic applications of 2-iodoxybenzoic acid (IBX) and similar oxidizing reagents based on the iodine(V) derivatives, the development and synthetic use of polymer-supported and recyclable polyvalent iodine reagents, the catalytic applications of organoiodine compounds, and structural studies of complexes and supramolecular assemblies of polyvalent iodine compounds.

The chemistry of polyvalent iodine has previously been covered in four books1–4 and several comprehensive review papers.5–17 Numerous reviews on specific classes of polyvalent iodine compounds and their synthetic applications have recently been published.18–61 Most notable are the specialized reviews on [hydroxy(tosyloxy)iodo]benzene,41 the chemistry and synthetic applications of iodonium salts,29,36,38,42,43,46,47,54,55 the chemistry of iodonium ylides,56–58 the chemistry of iminoiodanes,28 hypervalent iodine fluorides,27 electrophilic perfluoroalkylations,44 perfluoroorgano hypervalent iodine compounds,61 the chemistry of benziodoxoles,24,45 polymer-supported hypervalent iodine reagents,30 hypervalent iodine-mediated ring contraction reactions,21 application of hypervalent iodine in the synthesis of heterocycles,25,40 application of hypervalent iodine in the oxidation of phenolic compounds,32,34,50–53,60 oxidation of carbonyl compounds with organohypervalent iodine reagents,37 application of hypervalent iodine in (hetero)biaryl coupling reactions,31 phosphorolytic reactivity of o-iodosylcarboxylates,33 coordination of hypervalent iodine,19 transition metal catalyzed reactions of hypervalent iodine compounds,18 radical reactions of hypervalent iodine,35,39 stereoselective reactions of hypervalent iodine electrophiles,48 catalytic applications of organoiodine compounds,20,49 and synthetic applications of pentavalent iodine reagents.22,23,26,59

The main purpose of the present review is to summarize the data that appeared in the literature following publication of our previous reviews in 1996 and 2002. In addition, a brief introductory discussion of the most important earlier works is provided in each section. The review is organized according to the classes of organic polyvalent iodine compounds with emphasis on their synthetic application. Literature coverage is through July 2008.

Chemistry of Polyvalent Iodine

o-Quinone methides: intermediates underdeveloped and underutilized in organic synthesis

Cyclohexadienone ketals and quinols: four building blocks potentially useful for enantioselective synthesis.

ConspectusAn ortho-quinone methide (o-QM) is a highly reactive chemical motif harnessed by nature for a variety of purposes. Given its extraordinary reactivity and biological importance, it is surprising how few applications within organic synthesis exist. We speculate that their widespread use has been slowed by the complications that surround the preparation of their precursors, the harsh generation methods, and the omission of this stratagem from computer databases due to its ephemeral nature.About a decade ago, we discovered a mild anionic triggering procedure to generate transitory o-QMs at low temperature from readily available salicylaldehydes, particularly OBoc derivatives. This novel reaction cascade included both the o-QM formation and the subsequent consumption reaction. The overall transformation was initiated by the addition of the organometallic reagent, usually a Grignard reagent, which resulted in the formation of a benzyloxy alkoxide. Boc migration from the neighboring phenol produced a m...

/pdf/the-domestication-of-ortho-quinone-methides-4tj54z0v4m.pdf

The domestication of ortho-quinone methides.

https://chemistry.mdma.ch/hiveboard/palladium/pdf/Regioselective%20Oxidation%20of%20Phenols%20to%20o-Quinones%20with%20o-Iodoxybenzoic%20Acid%20(IBX).pdf

Regioselective Oxidation of Phenols to o-Quinones with o-Iodoxybenzoic Acid (IBX)

Recently,
three natural products have been identified, the epothilones,
eleutherobin, and discodermolide, whose mechanism of action is similar
to that of Taxol in that they stabilize microtubules and block cells in
the mitotic phase of the cell cycle. In this report, we have compared
and contrasted the effects of these new agents in Taxol-sensitive and
-resistant cell lines. We also have taken advantage of a human lung
carcinoma cell line, A549-T12, that was isolated as a Taxol-resistant
cell line and found to require low concentrations of Taxol (2–6
nm) for normal cell division. This study then examined the
ability of these new compounds to substitute for Taxol in sustaining
the growth of A549-T12 cells. Immunofluorescence and flow cytometry
have both indicated that the epothilones and eleutherobin, but not
discodermolide, can substitute for Taxol in this Taxol-dependent
cell line. In A549-T12 cells, the presence of Taxol significantly
amplified the cytotoxicity of discodermolide, and this phenomenon was
not observed in combinations of Taxol with either the epothilones or
eleutherobin. Median effect analysis using the combination index method
revealed a schedule-independent synergistic interaction between Taxol
and discodermolide in four human carcinoma cell lines, an effect that
was not observed between Taxol and epothilone B. Flow cytometry
revealed that concurrent exposure of A549 cells to Taxol and
discodermolide at doses that do not induce mitotic arrest caused an
increase in the hypodiploid population, thereby indicating that a
possible mechanism for the observed synergy is the potentiation of
apoptosis. Our results suggest that Taxol and discodermolide may
constitute a promising chemotherapeutic combination.

https://clincancerres.aacrjournals.org/content/clincanres/6/5/1978.full.pdf

Thomas R. R. Pettus

Papers

o-Quinone methides: intermediates underdeveloped and underutilized in organic synthesis

Cyclohexadienone ketals and quinols: four building blocks potentially useful for enantioselective synthesis.

The domestication of ortho-quinone methides.

Regioselective Oxidation of Phenols to o-Quinones with o-Iodoxybenzoic Acid (IBX)

Taxol and Discodermolide Represent a Synergistic Drug Combination in Human Carcinoma Cell Lines