Dilip Venkatrao Jarikote

A build–couple–pair strategy, including double-reductive amination macrocyclization, has been used to generate decorated macrocycles (eannaphanes) with an embedded triazole and monosaccharide. Biological screening led to the identification of an inducer of apoptosis in leukemic cells, which acts at least partially as a 5-HT2 antagonist.

Macrocycles containing embedded carbohydrates are found in nature. Tricholorin A and G, woodrosin, sophorolipid lactone, cycloviracin B1, glucolipsin A and ipomoeassins A–F are natural products with interesting biological properties. They have inspired synthesis of non‐natural macrocyclic structures which contain embedded carbohydrates. Glycophanes (hybrids of carbohydrates and cyclophanes) were prepared which show potential in host‐guest chemistry and which have been applied as rigid scaffolds for the synthesis of bivalent inhibitors of lectin binding to tumour cells. Macrocyclic neoglycoconjugates have also been prepared. These include macrocyclic neooligoaminodeoxysaccharides which bind to RNA regions containing either asymmetric internal loop or hairpin loop‐stem junctions, and vaccine candidates. Non‐natural macrolides having antibacterial and antifungal activity have been synthesised. Metathesis using Grubbs and Hoyveda‐Grubbs catalysts has been key to the successful generation of these compounds. Herein we review the recent application of metathesis to the synthesis of ipomoeassins A, B and F, glycophanes, neooligoaminodeoxysaccharides,macrolides and other macrocycles with embedded carbohydrates.

Double‐stranded DNA offers multiple binding sites to DNA stains. Measurements of noncovalently bound dye–nucleic acid complexes are, necessarily, measurements of an ensemble of chromophores. Thus, it is difficult to assign fluorescence properties to base‐pair‐specific binding modes of cyanine dyes or, vice versa, to obtain information about the local environment of cyanines in nucleic acids by using optical spectroscopy. The feasibility to stain DNA and simultaneously probe local perturbations by optical spectroscopy would be a valuable asset to nucleic acid research. So‐called FIT probes (forced intercalation probes) were used to pinpoint the location of the DNA stain thiazole orange (TO) in PNA⋅DNA duplexes. A detailed analysis of the base‐pair dependence of optical properties is provided and enforced binding of TO is compared with “classical” binding of free TO‐PRO1. UV‐visible absorbance, circular dichroism (CD) and fluorescence spectroscopy, and melting‐curve analyses confirmed site‐specific TO intercalation. Thiazole orange exhibited base‐specific responses that are not observed in noncovalent dye–nucleic acid complexes, such as an extraordinary dependence of the TO extinction coefficient (±60 % variation of the averaged ε_max of 57 000 M⁻¹ cm⁻¹) on nearest‐neighbor base pairs. TO signals hybridization, as shown by increases in the steady‐state fluorescence emission. Studies of TO fluorescence lifetimes in FIT–PNA and in DNA⋅DNA and PNA⋅DNA complexes highlighted four different fluorescence‐decay processes that may be closed or opened in response to matched or single‐mismatched hybridization. A very fast decay process (0.04–0.07 ns) and a slow decay process (2.33–3.95 ns) provide reliable monitors of hybridization, and the opening of a fast decay channel (0.22–0.48 ns) that resulted in an attenuation of the fluorescence emission is observed upon the formation of mismatched base pairs.