title: Mannich reaction: an approach for the synthesis of water soluble mulundocandin analogues.
abstract: Semisynthetic modifications at Hydroxy tyrosine (Htyr) unit of mulundocandin (1) were carried out to improve its aqueous solubility. A single step introduction of substituted aminomethyl groups at the ortho position(s) of phenolic hydroxyl of HTyr unit of mulundocandin has been achieved in 7-85% yield. The in vitro screening of Mannich products against Candida albicans and Aspergillus fumigatus, retained the in vivo activity of parent by oral and intraperitoneal route. Compound 20, showed significant improvement in activity over mulundocandin (1) and activity compares well with that of fluconazole.
authors.affiliation: Quest Institute of LifeSciences, Nicholas Piramal India Limited, Mulund (w), Mumbai 4000 80, India.
authors.forename: Bansi
authors.initials: B
authors.lastname: Lal
authors.forename: Vitthal Genbhau
authors.initials: VG
authors.lastname: Gund
authors.forename: Nandu Baban
authors.initials: NB
authors.lastname: Bhise
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Gangopadhyay
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D054714:Echinocandins; D008352:Mannich Bases / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D008826:Microbial Sensitivity Tests; D023421:Models, Animal; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility; D014867:Water / Q000737:chemistry*
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D008352:Mannich Bases; D010456:Peptides, Cyclic; D014867:Water; C052098:mulundocandin