Stereochemical Differentiation in the Simmons-Smith Reaction for Cyclopropanated Glucopyranose Derivatives as Molecular Probes for Glycosidases

Akiyama, Nanako; Noguchi, Shogo; Hashimoto, Minoru

doi:10.1271/bbb.110120

Cited by 3 publications

(2 citation statements)

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“…Hashimoto and coworkers were the first to report the synthesis of carba‐cyclophellitols, specifically carba‐cyclophellitols 3 and 10 . The key step in their synthesis was a Simmons–Smith cyclopropanation reaction (Et 2 Zn, CH 2 I 2 in CH 2 Cl 2 ) of a partially benzylated cyclohexene 6 (prepared by standard protecting‐group manipulations from diol 5 ).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Carba‐Cyclophellitols: a New Class of Carbohydrate Mimetics

et al. 2018

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Cyclophellitol and cyclophellitol aziridine are potent and irreversible inhibitors of retaining β‐glucosidases. They preferentially adopt a 4H3 half‐chair conformation, thereby mimicking the substrate‐transition‐state conformation characteristic of retaining β‐glucosidases. As a consequence, both compounds bind tightly to the enzyme active site, and attack of the catalytic nucleophile onto the epoxide/aziridine results in enzyme deactivation. Replacement of the epoxide oxygen in cyclophellitol by a (substituted) carbon yielded carba‐cyclophellitols, a conceptually new class of inhibitors of retaining β‐glucosidases, as we demonstrated in a recent communication. In this paper, in‐depth synthetic studies of this class of compounds are described, and the preparation of a comprehensive set of structurally and configurationally new carba‐cyclophellitols is presented.

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Section: Resultsmentioning

confidence: 99%

Synthesis of Carba‐Cyclophellitols: a New Class of Carbohydrate Mimetics

et al. 2018

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“…Carba‐cyclophellitols 48 were originally reported by Akiyama et al, as analogues of cyclophellitol ( 49 , Figure ), a 7‐oxa‐bicyclo[4.1.0]heptane isolated from Phellinus sp. fungus as a potent inhibitor of retaining β‐glucosidases.…”

Section: Endocyclic Oxygen Replacementmentioning

confidence: 99%

Design and synthesis of glycomimetics: Recent advances

Tamburrini

Colombo

Bernardi

2019

Medicinal Research Reviews

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In the past few decades, our understanding of glycan information‐encoding power has notably increased, thus leading to a significant growth also in the design and synthesis of glycomimetic probes. Combining data from multiple analytical sources, such as crystallography, nuclear magnetic resonance spectroscopy, and other biophysical methods (eg, surface plasmon resonance and carbohydrate microarrays) has allowed to shed light on the key interaction events between carbohydrates and their protein‐targets. However, the low metabolic stability of carbohydrates and their high hydrophilicity, which translates in low bioavailability, undermine their development as drugs. In this framework, the design of chemically modified analogues (called carbohydrate mimics or glycomimetics) appears as a valid alternative for the development of therapeutic agents. Glycomimetics, as structural and functional mimics of carbohydrates, can replace the native ligands in the interaction with target proteins, but are designed to show enhanced enzymatic stability and bioavailability and, possibly, an improved affinity and selectivity toward the target. In the present account, we specifically focus on the most recent advances in the design and synthesis of glycomimetics. In particular, we highlight the efforts of the scientific community in the development of straightforward synthetic procedures for the preparation of sugar mimics and in their preliminary biological evaluation.

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