Mannich reaction: an approach for the synthesis of water soluble mulundocandin analogues.
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.
Lal
Bansi
B
Quest Institute of LifeSciences, Nicholas Piramal India Limited, Mulund (w), Mumbai 4000 80, India.
Gund
Vitthal Genbhau
VG
Bhise
Nandu Baban
NB
Gangopadhyay
Ashok Kumar
AK
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*
D000935:Antifungal Agents; D054714:Echinocandins; D008352:Mannich Bases; D010456:Peptides, Cyclic; D014867:Water; C052098:mulundocandin