抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

C–H activation has surfaced as an increasingly powerful tool for molecular sciences, with notable applications to material sciences, crop protection, drug discovery, and pharmaceutical industries, among others. Despite major advances, the vast majority of these C–H functionalizations required precious 4d or 5d transition metal catalysts. Given the cost-effective and sustainable nature of earth-abundant first row transition metals, the development of less toxic, inexpensive 3d metal catalysts for C–H activation has gained considerable recent momentum as a significantly more environmentally-benign and economically-attractive alternative. Herein, we provide a comprehensive overview on first row transition metal catalysts for C–H activation until summer 2018.

3d Transition Metals for C-H Activation.

1.1. General Reactivity of Alkyne-Gold(I) Complexes
For centuries, gold had been considered a precious, purely decorative inert metal. It was not until 1986 that Ito and Hayashi described the first application of gold(I) in homogeneous catalysis.1 More than one decade later, the first examples of gold(I) activation of alkynes were reported by Teles2 and Tanaka,3 revealing the potential of gold(I) in organic synthesis. Now, gold(I) complexes are the most effective catalysts for the electrophilic activation of alkynes under homogeneous conditions, and a broad range of versatile synthetic tools have been developed for the construction of carbon–carbon or carbon–heteroatom bonds.

Gold(I) complexes selectively activate π-bonds of alkynes in complex molecular settings,4−10 which has been attributed to relativistic effects.11−13 In general, no other electrophilic late transition metal shows the breadth of synthetic applications of homogeneous gold(I) catalysts, although in occasions less Lewis acidic Pt(II) or Ag(I) complexes can be used as an alternative,9,10,14,15 particularly in the context of the activation of alkenes.16,17 Highly electrophilic Ga(III)18−22 and In(III)23,24 salts can also be used as catalysts, although often higher catalyst loadings are required.

In general, the nucleophilic Markovnikov attack to η2-[AuL]+-activated alkynes 1 forms trans-alkenyl-gold complexes 2 as intermediates (Scheme 1).4,5a,9,10,12,25−29 This activation mode also occurs in gold-catalyzed cycloisomerizations of 1,n-enynes and in hydroarylation reactions, in which the alkene or the arene act as the nucleophile.



Scheme 1

Anti-Nucleophilic Attack to η2-[AuL]+-Activated Alkynes

/pdf/gold-i-catalyzed-activation-of-alkynes-for-the-construction-50i37g5kgj.pdf

Gold(I)-Catalyzed Activation of Alkynes for the Construction of Molecular Complexity

This Perspective illustrates the defining characteristics of free radical chemistry, beginning with its rich and storied history. Studies from our laboratory are discussed along with recent developments emanating from others in this burgeoning area. The practicality and chemoselectivity of radical reactions enable rapid access to molecules of relevance to drug discovery, agrochemistry, material science, and other disciplines. Thus, these reactive intermediates possess inherent translational potential, as they can be widely used to expedite scientific endeavors for the betterment of humankind.

Radicals: Reactive Intermediates with Translational Potential

In this critical review the applications of gold catalysed reactions in total synthesis during the years since our last article are reviewed. At the end of this article a literature analysis is conducted to evaluate the progress in this field.

Gold catalysis in total synthesis – recent achievements

Cofactor-mimetic aerobic oxidation has conceptually merged with catalysis of syngas reactions to form a wide range of Markovnikov-selective olefin radical hydrofunctionalizations. We cover the development of the field and review contributions to reaction invention, mechanism, and application to complex molecule synthesis. We also provide a mechanistic framework for understanding this compendium of radical reactions.

/pdf/mn-fe-and-co-catalyzed-radical-hydrofunctionalizations-of-3ukqn8iif4.pdf

Mn-, Fe-, and Co-Catalyzed Radical Hydrofunctionalizations of Olefins

Cycloisomerizations of enynes are probably the most representative carbon–carbon bond forming reactions catalyzed by electrophilic metal complexes. These transformations are synthetically useful because chemists can use them to build complex architectures under mild conditions from readily assembled starting materials. However, these transformations can have complex mechanisms. In general, gold(I) activates alkynes in the presence of any other unsaturated functional group by forming an (η2-alkyne)–gold complex. This species reacts readily with nucleophiles, including electron-rich alkenes. In this case, the reaction forms cyclopropyl gold(I) carbene-like intermediates. These can come from different pathways depending on the substitution pattern of the alkyne and the alkene. In the absence of external nucleophiles, 1,n-enynes can form products of skeletal rearrangement in fully intramolecular reactions, which are mechanistically very different from metathesis reactions initiated by the [2 + 2] cycloadditio...

https://pubs.acs.org/doi/pdf/10.1021/ar400174p

Gold-Catalyzed Rearrangements and Beyond

https://pubs.rsc.org/en/Content/ArticlePDF/2014/CC/C3CC45518A

Intriguing mechanistic labyrinths in gold(I) catalysis

We report the discovery of an outstanding reductant for metal-catalyzed radical hydrofunctionalization reactions. Observations of unexpected silane solvolysis distributions in the HAT-initiated hydrogenation of alkenes reveal that phenylsilane is not the kinetically preferred reductant in many of these transformations. Instead, isopropoxy(phenyl)silane forms under the reaction conditions, suggesting that alcohols function as important silane ligands to promote the formation of metal hydrides. Study of its reactivity showed that isopropoxy(phenyl)silane is an exceptionally efficient stoichiometric reductant, and it is now possible to significantly decrease catalyst loadings, lower reaction temperatures, broaden functional group tolerance, and use diverse, aprotic solvents in iron- and manganese-catalyzed hydrofunctionalizations. As representative examples, we have improved the yields and rates of alkene reduction, hydration, hydroamination, and conjugate addition. Discovery of this broadly applicable, chem...

/pdf/ph-i-pro-sih2-an-exceptional-reductant-for-metal-catalyzed-3w4rxjs646.pdf

Ph(i-PrO)SiH2: An Exceptional Reductant for Metal-Catalyzed Hydrogen Atom Transfers

Cobalt/nickel-dual catalyzed hydroarylation of terminal olefins with iodoarenes builds complexity from readily available starting materials, with a high preference for the Markovnikov (branched) product Here, we advance a mechanistic model of this reaction through the use of reaction progress kinetic analysis (RPKA), radical clock experiments, and stoichiometric studies Through exclusion of competing hypotheses, we conclude that the reaction proceeds through an unprecedented alkylcobalt to nickel direct transmetalation Demonstration of catalytic alkene prefunctionalization, via spectroscopic observation of an organocobalt species, distinguishes this Csp2–Csp3 cross-coupling method from a conventional transmetalation process, which employs a stoichiometric organometallic nucleophile, and from a bimetallic oxidative addition of an organohalide across nickel, described by radical scission and subsequent alkyl radical capture at a second nickel center A refined understanding of the reaction leads to an op

Carla Obradors

Papers

Mn-, Fe-, and Co-Catalyzed Radical Hydrofunctionalizations of Olefins

Gold-Catalyzed Rearrangements and Beyond

Intriguing mechanistic labyrinths in gold(I) catalysis

Ph(i-PrO)SiH2: An Exceptional Reductant for Metal-Catalyzed Hydrogen Atom Transfers

Mechanistic Interrogation of Co/Ni-Dual Catalyzed Hydroarylation