title: Further evidence on the favorable role of the anomeric effect on the cleavage of HepDirect and cyclophosphamide prodrugs.
abstract: On the basis of previous conformational and configurational studies of 4-aryl-substituted cyclophosph(on)ates derived from d-xylofuranose derivatives, wherein it was proposed that the anomeric effect is involved in the spontaneous isomerization of the P atom and the C4 carbon, and consequently, this unusual behavior was associated with the cleavage of the HepDirect prodrugs. We synthesized an analogous series of 2-amino-2-oxo-1,3,2-dioxaphosphorinanes and performed a conformational and configurational analysis in solution and the solid state followed by an examination of their mutagenic activity. The results showed that the 2-amino-2-oxo-1,3,2-dioxaphosphorinanes with the largest mutagenic activity contain either a 4-methoxyphenyl or 4-fluorophenyl group at C4 carbon and presented a major chair conformation, which is prone to weaken the C4-O3 bond via the anomeric effect and facilitates the cleavage for the release of the biologically active metabolite.
authors.affiliation: Centro de Investigación de la Facultad de Ciencias Químicas, BUAP (Benemérita Universidad Autónoma de Puebla) , 14 Sur Esq. San Claudio, San Manuel, 72570 Puebla, Mexico.
authors.forename: Fernando
authors.initials: F
authors.lastname: Sartillo-Piscil
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintero
authors.forename: Silvano
authors.initials: S
authors.lastname: Cruz-Gregorio
authors.forename: Javier
authors.initials: J
authors.lastname: Espinosa-Aguirre
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Elinos-Baez
authors.forename: Herbert
authors.initials: H
authors.lastname: Höpfl
authors.forename: Abel
authors.initials: A
authors.lastname: Serrano
mesh_terms: D003520:Cyclophosphamide / Q000737:chemistry*; D007536:Isomerism; D008958:Models, Molecular; D008968:Molecular Conformation; D009943:Organophosphorus Compounds / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry*
chemical_list: D009943:Organophosphorus Compounds; D011355:Prodrugs; D003520:Cyclophosphamide