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

The Huisgen 1,3-dipolar cycloaddition reaction of organic azides and alkynes has gained considerable attention in recent years due to the introduction in 2001 of Cu(1) catalysis by Tornoe and Meldal, leading to a major improvement in both rate and regioselectivity of the reaction, as realized independently by the Meldal and the Sharpless laboratories. The great success of the Cu(1) catalyzed reaction is rooted in the fact that it is a virtually quantitative, very robust, insensitive, general, and orthogonal ligation reaction, suitable for even biomolecular ligation and in vivo tagging or as a polymerization reaction for synthesis of long linear polymers. The triazole formed is essentially chemically inert to reactive conditions, e.g. oxidation, reduction, and hydrolysis, and has an intermediate polarity with a dipolar moment of ∼5 D. The basis for the unique properties and rate enhancement for triazole formation under Cu(1) catalysis should be found in the high ∆G of the reaction in combination with the low character of polarity of the dipole of the noncatalyzed thermal reaction, which leads to a considerable activation barrier. In order to understand the reaction in detail, it therefore seems important to spend a moment to consider the structural and mechanistic aspects of the catalysis. The reaction is quite insensitive to reaction conditions as long as Cu(1) is present and may be performed in an aqueous or organic environment both in solution and on solid support.

Cu-catalyzed azide-alkyne cycloaddition.

The direct functionalization of C-H bonds in organic compounds has recently emerged as a powerful and ideal method for the formation of carbon-carbon and carbon-heteroatom bonds. This Review provides an overview of C-H bond functionalization strategies for the rapid synthesis of biologically active compounds such as natural products and pharmaceutical targets.

C-H bond functionalization: emerging synthetic tools for natural products and pharmaceuticals

Functionalizing traditionally inert carbon–hydrogen bonds represents a powerful transformation in organic synthesis, providing new entries to valuable structural motifs and improving the overall synthetic efficiency. C–H bond activation, however, often necessitates harsh reaction conditions that result in functional group incompatibilities and limited substrate scope. An understanding of the reaction mechanism and rational design of experimental conditions have led to significant improvement in both selectivity and applicability. This critical review summarizes and discusses endeavours towards the development of mild C–H activation methods and wishes to trigger more research towards this goal. In addition, we examine select examples in complex natural product synthesis to demonstrate the synthetic utility of mild C–H functionalization (84 references).

Towards mild metal-catalyzed C–H bond activation

C-H bonds are ubiquitous in organic compounds. It would, therefore, appear that direct functionalization of substrates by activation of C-H bonds would eliminate the multiple steps and limitations associated with the preparation of functionalized starting materials. Regioselectivity is an important issue because organic molecules can contain a wide variety of C-H bonds. The use of a directing group can largely overcome the issue of regiocontrol by allowing the catalyst to come into proximity with the targeted C-H bonds. A wide variety of functional groups have been evaluated for use as directing groups in the transformation of C-H bonds. In 2005, Daugulis reported the arylation of unactivated C(sp(3))-H bonds by using 8-aminoquinoline and picolinamide as bidentate directing groups, with Pd(OAc)2 as the catalyst. Encouraged by these promising results, a number of transformations of C-H bonds have since been developed by using systems based on bidentate directing groups. In this Review, recent advances in this area are discussed.

Catalytic Functionalization of C(sp2) ? H and C(sp3) ? H Bonds by Using Bidentate Directing Groups

Efficient preparation of β-hydroxy aspartic acid and its derivatives

Abstract Sulfur–heteroatom bonds such as S–S and S–N are found in a variety of natural products and often play important roles in biological processes. Despite their widespread applications, the synthesis of sulfenamides, which feature S–N bonds that may be cleaved under mild conditions, remains underdeveloped. Here, we report a method for synthesis of N -acyl sulfenamides via copper-catalyzed nitrene-mediated S -amidation reaction of thiols with dioxazolones. This method is efficient, convenient, and broadly applicable. Moreover, the resulting N -acetyl sulfenamides are highly effective S -sulfenylation reagents for the synthesis of unsymmetrical disulfides under mild conditions. The S -sulfenylation protocol enables facile access to sterically demanding disulfides that are difficult to synthesize by other means. 

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Synthesis of N-acyl sulfenamides via copper catalysis and their use as S-sulfenylating reagents of thiols

Nature Communications 5: Article number 4159 doi: (2014); Published 13 June 2014; Updated 12 September 2014 The original version of this Article contained a typographical error in the spelling of ‘Alzheimer’s’ in the title of the paper. This has now been corrected in both the PDF and HTML version ofthe Article.

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Corrigendum: Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzheimer’s disease model

Construction of Peptide Macrocycles via Palladium-Catalyzed Multiple S-Arylation: An Effective Strategy to Expand the Structural Diversity of Cross-Linkers.

An efficient method has been developed for the synthesis of indoline compounds from picolinamide (PA)-protected β-arylethylamine substrates via palladium-catalyzed intramolecular amination of ortho-C(sp(2))-H bonds. These reactions feature high efficiency, low catalyst loadings, mild operating conditions, and the use of inexpensive reagents.

Gong Chen

Papers

Efficient preparation of β-hydroxy aspartic acid and its derivatives

Synthesis of N-acyl sulfenamides via copper catalysis and their use as S-sulfenylating reagents of thiols

Corrigendum: Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzheimer’s disease model

Construction of Peptide Macrocycles via Palladium-Catalyzed Multiple S-Arylation: An Effective Strategy to Expand the Structural Diversity of Cross-Linkers.

Improved Protocol for Indoline Synthesis via Palladium-Catalyzed Intramolecular C(sp2)—H Amination.