Alkylation and some physicoc hemical characteristics of 6,7- and 7,8- dihydroxycoumarins

Zagorevskii, V. A.; Kirsanova, Z. D.; Persianova, I. V.; Zykov, D. A.

doi:10.1007/bf00472114

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“…The phenolate ion 28 is then alkylated by cephalosporin 4 in the presence of NaI to form intermediate 29 . The experimental p Ka of the phenol in mono-alkylated catechols is consistently reported to be several log units higher [ 50 , 51 ] than the most acidic phenol in their non-alkylated precursors, hence a second phenolate alkylation reaction is not favoured under these conditions. Rather, phenol 29 undergoes an intramolecular Michael addition to form the spiro-cephalosporin 30 , with initial attack on the convex face of the cephalosporin core, followed by protonation on the face opposite the newly-introduced, bulky catechol unit to set the observed (2′ S ,2 R ) stereochemistry.…”

Section: Resultsmentioning

confidence: 99%

New Methods for the Synthesis of Spirocyclic Cephalosporin Analogues

2021

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Spiro compounds provide attractive targets in drug discovery due to their inherent three-dimensional structures, which enhance protein interactions, aid solubility and facilitate molecular modelling. However, synthetic methodology for the spiro-functionalisation of important classes of penicillin and cephalosporin β-lactam antibiotics is comparatively limited. We report a novel method for the generation of spiro-cephalosporin compounds through a Michael-type addition to the dihydrothiazine ring. Coupling of a range of catechols is achieved under mildly basic conditions (K2CO3, DMF), giving the stereoselective formation of spiro-cephalosporins (d.r. 14:1 to 8:1) in moderate to good yields (28−65%).

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Section: Resultsmentioning

confidence: 99%