Improvement of the synthesis of diphenylmethyl 7β-(o-hydroxy)benzylideneamino-3-hydroxymethyl-3-cephem-4-carboxylate

López, José Miguel Túñez; Rodríguez, Zalua; Valdes, Barbara; Vélez, Hermán; Agüero, Juan; Fini, Adamo; González, Maritza

doi:10.1016/s0014-827x(01)01115-6

Cited by 2 publications

(1 citation statement)

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“…A key step in the transformation was selective removal of the 3‘-acetate. Various protocols have been described in the literature using hydroxide solutions at low temperature; however, we did not find these to be robust or reliable processes. The enzyme acetylesterase from orange peel (commercially available) is known to be selective and efficient (if somewhat expensive) for this transformation and this gave reproducible results in our work.…”

Section: Resultscontrasting

confidence: 56%

Toward the Development of a Cephalosporin-Based Dual-Release Prodrug for Use in ADEPT

Grant

Smyth

2004

J. Org. Chem.

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In previous work we have shown that a cephalosporin structure bearing an S-aminosulfenimine at the 7-position behaved as a beta-lactamase-dependent dual-release prodrug. Scission of the beta-lactam ring of such a structure led to the rapid loss of the sulfur-attached side chain moiety via an intramolecular displacement, while the 3'-group was lost via the well-established elimination process at that position. In the present work we report on an evaluation of the scope and limitations of exploiting the S-aminosulfenimine functionality to generate a cephalosporin-based prodrug incorporating two biologically active components. Starting from 7-ACA, a viable synthetic cycle was put in place that avoided formation of the Delta(2) isomer throughout and that allowed incorporation of aminoglutethimide at the 3'-position and of a tosyl S-aminosulfenimine at the 7-position. The direct incorporation of a biologically active sulfonamide (ethoxzolamide) or a sulfamate (coumate) at this latter position was not achieved as a result of the difficulty of generating the corresponding sulfur diimides. An indirect route for the formation of an S-aminosulfenimine was put in place, as was a general method of alkylation (Mitsunobu reaction) of the tosyl S-aminosulfenimine following its incorporation.

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Section: Resultscontrasting

confidence: 56%