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 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

140 years ago Adolf von Baeyer proposed the structure of a heteroaromatic compound which revolutionized organic and medical chemistry: indole. After more than a century, indole itself and the complexity of naturally occurring indole derivatives continue to inspire and influence developments in synthetic chemistry. In particular, the ubiquitous presence of indole rings in pharmaceuticals, agrochemicals, and functional materials are testament to the ever increasing interest in the design of mild and efficient synthetic routes to functionalized indole derivatives. This Review emphasizes the achievements in the selective catalytic functionalization of indoles (C-C bond-forming processes) over the last four years.

Catalytic Functionalization of Indoles in a New Dimension

Catalysis with chiral secondary amines (asymmetric aminocatalysis) has become a well-established and powerful synthetic tool for the chemo- and enantioselective functionalization of carbonyl compounds. In the last eight years alone, this field has grown at such an extraordinary pace that it is now recognized as an independent area of synthetic chemistry, where the goal is the preparation of any chiral molecule in an efficient, rapid, and stereoselective manner. This has been made possible by the impressive level of scientific competition and high quality research generated in this area. This Review describes this "Asymmetric Aminocatalysis Gold Rush" and charts the milestones in its development. As in all areas of science, progress depends on human effort.

Asymmetric aminocatalysis--gold rush in organic chemistry.

Die direkte Funktionalisierung von C-H-Bindungen in organischen Molekulen hat sich in jungster Zeit zu einer wirksamen und idealen Methode entwickelt, mit der Kohlenstoff-Kohlenstoff- und Kohlenstoff-Heteroatom-Bindungen geknupft werden konnen. Der Aufsatz gibt einen Uberblick uber die Strategien, die durch Funktionalisierung von C-H-Bindungen eine rasche Synthese von biologisch aktiven Verbindungen wie Naturstoffen und pharmazeutischen Zielsubstanzen ermoglichen.

Funktionalisierung von C‐H‐Bindungen: neue Synthesemethoden für Naturstoffe und Pharmazeutika

Herein we report the first use of vinyl and heteroaryl trifluoroborate salts as viable substrates for amine-catalyzed conjugate additions. The application of LUMO-lowering iminium catalysis has enabled the highly regio- and enantioselective 1,4-addition of rationally designed trifluoroborate salt nucleophiles to α,β-unsaturated aldehydes. Imidazolidinone 2•HCl was found to catalyze the addition of various BF3K-derived heteroaryl and vinyl species to a range of enals with excellent levels of enantioselectivity. Importantly, the use of these salts can enable nontraditional regiocontrol as part of a Friedel−Crafts pathway. Boronic acids can also be employed as viable π-nucleophiles for these asymmetric conjugate additions provided that in situ activation to the corresponding boronate species is accomplished. While BF3K salts are routinely employed in transition metal catalysis, to our knowledge, this is the first use of this activation group for organic catalysis or Friedel−Crafts alkylations.

Organocatalytic vinyl and Friedel-Crafts alkylations with trifluoroborate salts.

The frondosins are a family of marine sesquiterpenes isolated from the sponge Dysidea frondosa that exhibit biological activities ranging from anti-inflammatory properties to potential application in anticancer and HIV therapy. Herein, a concise enantioselective total synthesis of (+)-frondosin B is described which requires a total of three chemical steps. The enantioselective conjugate addition of a benzofuran-derived boronic acid to crotonaldehyde in the presence of an imidazolidinone organocatalyst builds the critical stereogenic center of frondosin B in the first operation, while the remaining two ring systems of this natural product are installed in the two subsequent steps. A combination of X-ray crystallographic data, deuterium labeling, and chemical correlation studies provides further evidence as to the correct absolute stereochemical assignment of (+)-frondosin B.

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The organocatalytic three-step total synthesis of (+)-frondosin B

A computer software application, graphical user interface, and method for entering information concerning a complex business situation (16), refining such information in a stepwise manner through the interface, generating a list of effective actions for addressing such a business situation, and storing such information in a knowledge base adapted for future query and reporting use of such a complex business situations (16), is provided. A set of screen sequences (14, 16, 18) allows entry of specific aspects of such a situation to generate an action list. A situation appraisal sequence allows entry of concerns stemming from the situation to prioritize such concerns. A problem analysis sequence (14) allows entry of causes of a problem, and refining the causes to determine a true cause. A decision analysis sequence (14) allows entry of alternatives concerning a decision, and refines such alternatives to determine one which suits the objective.

Method and apparatus for problem solving, decision making, storing, analyzing, retrieving enterprisewide knowledge and conclusive data

A short approach is elaborated which affords the desired title compound (VI) together with lower amounts of its double bond isomer.

Sandra Lee

Papers

Organocatalytic vinyl and Friedel-Crafts alkylations with trifluoroborate salts.

The organocatalytic three-step total synthesis of (+)-frondosin B

Method and apparatus for problem solving, decision making, storing, analyzing, retrieving enterprisewide knowledge and conclusive data

The Organocatalytic Three-Step Total Synthesis of (+)-Frondosin B.

Organocatalytic Vinyl and Friedel—Crafts Alkylations with Trifluoroborate Salts.