Building the Housane: Diastereoselective Synthesis and Characterization of Bicyclo[2.1.0]pentane Carboxylic AcidsClick to copy article linkArticle link copied!
- Volodymyr V. SemenoVolodymyr V. SemenoEnamine Ltd. (www.enamine.net), Chervonotkatska Street 78, Kyiv 02094, UkraineMore by Volodymyr V. Semeno
- Vadym O. VasylchenkoVadym O. VasylchenkoEnamine Ltd. (www.enamine.net), Chervonotkatska Street 78, Kyiv 02094, UkraineNational Technical University of Ukraine ″Igor Sikorsky Kyiv Polytechnic Institute″, Prospect Peremogy 37, Kyiv 03056, UkraineMore by Vadym O. Vasylchenko
- Bohdan V. VashchenkoBohdan V. VashchenkoEnamine Ltd. (www.enamine.net), Chervonotkatska Street 78, Kyiv 02094, UkraineTaras Shevchenko National University of Kyiv, Volodymyrska Street 60, Kyiv 01601, UkraineMore by Bohdan V. Vashchenko
- Dmytro O. LutsenkoDmytro O. LutsenkoEnamine Ltd. (www.enamine.net), Chervonotkatska Street 78, Kyiv 02094, UkraineMore by Dmytro O. Lutsenko
- Rustam T. IminovRustam T. IminovEnamine Ltd. (www.enamine.net), Chervonotkatska Street 78, Kyiv 02094, UkraineMore by Rustam T. Iminov
- Olesia B. VolovenkoOlesia B. VolovenkoEnamine Ltd. (www.enamine.net), Chervonotkatska Street 78, Kyiv 02094, UkraineMore by Olesia B. Volovenko
- Oleksandr O. Grygorenko*Oleksandr O. Grygorenko*E-mail: [email protected]Enamine Ltd. (www.enamine.net), Chervonotkatska Street 78, Kyiv 02094, UkraineTaras Shevchenko National University of Kyiv, Volodymyrska Street 60, Kyiv 01601, UkraineMore by Oleksandr O. Grygorenko
Abstract
An approach to 1,3-disubstitued bicyclo[2.1.0]pentane (housane) derivatives was developed. The method relied on lithium bis(trimethylsilyl)amide-mediated intramolecular cyclization of trisubstitued cyclopentane carboxylates bearing a leaving group (at the C-4 position) and an additional substituent (at the C-3 atom), in turn synthesized from cyclopent-3-ene carboxylate. The synthetic sequence allowed for the preparation of both cis- and trans-1,3-disubstituted housane-1-carboxylic acids in diastereoselective manner on up to 80 g scale. In particular, bicyclic γ-amino acids—γ-aminobutyric acid analogues—were synthesized. It was shown that the bicyclo[2.1.0]pentane did not significantly affect pKa of the corresponding derivatives and slightly increased their hydrophilicity (by 0.07–0.25 Log P units) as compared to cyclopentane. X-ray diffraction studies showed that cis- and trans-1,3-disubstituted housanes can be considered as flattened analogues of the corresponding cyclopentane derivatives with fixed envelope conformation of the five-membered ring.
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