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Organic chemistry. Strain-release amination

, : Organic chemistry. Strain-release amination. Science 351(6270): 241-246

To optimize drug candidates, modern medicinal chemists are increasingly turning to an unconventional structural motif: small, strained ring systems. However, the difficulty of introducing substituents such as bicyclo[1.1.1]pentanes, azetidines, or cyclobutanes often outweighs the challenge of synthesizing the parent scaffold itself. Thus, there is an urgent need for general methods to rapidly and directly append such groups onto core scaffolds. Here we report a general strategy to harness the embedded potential energy of effectively spring-loaded C-C and C-N bonds with the most oft-encountered nucleophiles in pharmaceutical chemistry, amines. Strain-release amination can diversify a range of substrates with a multitude of desirable bioisosteres at both the early and late stages of a synthesis. The technique has also been applied to peptide labeling and bioconjugation.


PMID: 26816372

DOI: 10.1126/science.aad6252

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Timsit, Y.; Shatzky-Schwartz, M.; Shakked, Z., 1999: Left-handed DNA crossovers. Implications for DNA-DNA recognition and structural alterations. The close approach of DNA segments participates in many biological functions including DNA condensation and DNA processing. Previous crystallographic studies have shown that B-DNA self-fitting by mutual groove-backbone interaction produces right-h...

Mcintire P.W.; Carey A.B., 1989: A microhistological technique for analysis of food habits of mycophagous rodents. U S Forest Service Research Paper PNW (404): I-IV, 1-16

Pope, B.; Way, M.; Matsudaira, P., T.; Weeds, A., 1994: Characterization of the F-actin binding domains of villin: Classification of F-actin binding proteins into two groups according to their binding sites on actin. The F-actin binding properties of chicken villin, its headpiece and domains 2-3 (V2-3) have been analysed to identify sites involved in bundle formation. Headpiece and V2-3 bind actin with K-d values of apprx 7 mu-M and apprx 0.3 mu-M, respectivel...

Baranov, O.G.; Gubka, A.V., 1984: Cystiform dilatation of the common bile duct. Klinicheskaia Khirurgiia: 62-62

Wood, M., 1992: Seed for tommorrow. Agricultural research US Department of Agriculture Agricultural Research Service 40(4): 30

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