141524-74-5Relevant articles and documents
4,5-Disubstituted N-Methylimidazoles as Versatile Building Blocks for Defined Side-Chain Introduction
Przybyla, Daniel,Nubbemeyer, Udo
, p. 695 - 703 (2017)
Fungerin is a 1,4,5-trisubstituted imidazole natural product characterised by a broad spectrum of antifungal activities. We planned to develop flexible strategies to access to such compounds. Imidazoles bearing suitable anchor groups at C-4 and C-5 allow the introduction of various substituted side-chains, generating libraries of fungerin derivatives for biological tests. Starting from commercially available reactants, two N-methyl 4,5-substituted imidazole core units were synthesised. Derivatives of type 1 contained two orthogonally protected C-1 anchors. Selective side-chain introduction was achieved through a sequence of Grignard coupling at C-5 to replace a tosylate and a Horner olefination through an aldehyde attached to C-4. Two target fungerin derivatives were synthesised. Since the organometallic substitution of the C-5-CH2-positioned leaving group proved to suffer from limitations concerning potential competing side-reactions, a type 2 imidazole core was built up. These structures had a halogen centre at C-4 and a hydroxyethyl anchor at C-5. Now, selective side-chain introduction allowed us to use Julia olefination to form the allyl side-chain at C-5 and Heck reactions to introduce the C-4 acryl substituents. Eight derivatives, including fungerin, were synthesised by this latter strategy, without producing any regioisomers. The second approach had the advantage that various side-chains could be coupled at C-4 and C-5 in two final steps. Thus, this strategy represents a versatile way to build up libraries of fungerin derivatives for biological testing.
HEMOGLOBIN MODIFIER COMPOUNDS AND USES THEREOF
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Paragraph 00639-00641, (2018/02/28)
Described herein are compounds, including pharmaceutically acceptable salts thereof, methods of making such compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat, prevent or diagnose blood-based diseases, disorders or conditions.
Carboxylate protection for the synthesis of 4,5-disubstituted 1-methylimidazoles
Shapiro,Gomez-Lor
, p. 5524 - 5526 (2007/10/02)
Using the carboxylate function as a readily removed blocking group for the 2-position, a regioselective synthesis of diverse 4,5-disubstituted 1-methylimidazoles has been developed starting from 1-methyltribromoimidazole, 5.
