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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

Examination of nature's favorite molecules reveals a striking preference for making carbon-heteroatom bonds over carbon-carbon bonds-surely no surprise given that carbon dioxide is nature's starting material and that most reactions are performed in water. Nucleic acids, proteins, and polysaccharides are condensation polymers of small subunits stitched together by carbon-heteroatom bonds. Even the 35 or so building blocks from which these crucial molecules are made each contain, at most, six contiguous C-C bonds, except for the three aromatic amino acids. Taking our cue from nature's approach, we address here the development of a set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new compounds and combinatorial libraries through heteroatom links (C-X-C), an approach we call "click chemistry". Click chemistry is at once defined, enabled, and constrained by a handful of nearly perfect "spring-loaded" reactions. The stringent criteria for a process to earn click chemistry status are described along with examples of the molecular frameworks that are easily made using this spartan, but powerful, synthetic strategy.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/1521-3773%2820010601%2940%3A11%3C2004%3A%3AAID-ANIE2004%3E3.0.CO%3B2-5

Click Chemistry: Diverse Chemical Function from a Few Good Reactions.

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

Marine natural products.

CA : A Cancer Journal for Clinicians

Hydrozirconation of allenes followed by in situ transmetalation to dialkylzinc leads to the formation of an allylic zinc species that, upon addition of aldimines to the reaction mixture, provides homoallylic amines in 64−85% yield.

/pdf/synthesis-of-homoallylic-amines-by-hydrozirconation-imine-1omh3ddff5.pdf

Synthesis of Homoallylic Amines by Hydrozirconation—Imine Addition of Allenes.

Inhibition of tyrosine kinase Fgr prevents radiation-induced pulmonary fibrosis (RIPF)

The benzofuranone-indolyloxazole fragment of the polycyclic marine natural product diazonamide A was prepared from tryptamine. The oxazole ring was synthesized from an α keto-indole via cyclodehydration with Ph3PCl3CCCl3, and after selective Stille biaryl coupling with 2-iodo-6-stannylphenol, the benzofuranone ring was constructed by an intramolecular Heck annulation of an α,β-unsaturated aryl ester.

Synthetic Studies Toward Diazonamide A. Preparation of the Benzofuranone-Indolyloxazole Fragment.

After the isolation of the bioactive polyether bistramide C from the marine ascidian Lissoclinum bistratum in 1988, NMR spectroscopic investigations over the next 12 years reduced the total number of possible stereoisomers of this compound from 1024 to 32. Based on the preparation of segments of the natural product as well as the total synthesis of a randomly selected stereoisomer of bistramide C, the stereochemical puzzle could be further simplified to eight possible stereoisomers. A convergent three-segment coupling strategy, the use of a common, D-glucose-derived intermediate for the preparation of pyran rings in two segments, a stereoselective photo-spiroketalization, and the use of azides to minimize protective group manipulations before segment couplings are highlights of the synthetic approach. The total synthesis also provided the key segments for a chiroptical analysis according to van't Hoff's principle of optical superposition, which was crucial for the assignment of a sole relative and absolute configuration of the natural product. Bistramide C represents therefore the first member of this class of structurally unusual marine polyethers whose configuration is known as a result of the combined use of synthetic and chiroptical tools.

Peter Wipf

Papers

Synthesis of Homoallylic Amines by Hydrozirconation—Imine Addition of Allenes.

Inhibition of tyrosine kinase Fgr prevents radiation-induced pulmonary fibrosis (RIPF)

Synthetic Studies Toward Diazonamide A. Preparation of the Benzofuranone-Indolyloxazole Fragment.

Total Synthesis of a Stereoisomer of Bistramide C and Assignment of Configuration of the Natural Product.

Efficient Synthesis of 1,4‐Dihydro‐2H‐isoquinoline‐3,5,8‐triones via Cyclobutene Ring Expansion.