Divergent Synthesis of Three Classes of Antifungal Amphiphilic Kanamycin Derivatives

Authors

Qian Zhang, Utah State University
Madher N. AlFindee, Utah State University
Jaya P. Shrestha, Utah State University
Vincent P. N. Nziko, Utah State University
Yukie Kawasaki, Utah State UniversityFollow
Xinrui Peng, Utah State University
Jon Y. Takemoto, Utah State UniversityFollow
Cheng-Wei Tom Chang, Utah State UniversityFollow

Document Type

Article

Journal/Book Title

Journal of Organic Chemistry

Publication Date

10-7-2016

Publisher

American Chemical Society

Volume

81

Issue

22

First Page

10651

Last Page

10663

Abstract

A concise and novel method for site-selective alkylation of 1,3,6′,3″-tetraazidokanamycin has been developed that leads to the divergent synthesis of three classes of kanamycin A derivatives. These new amphiphilic kanamycin derivatives bearing alkyl chains length of 4, 6, 7, 8, 9, 10, 12, 14, and 16 have been tested for their antibacterial and antifungal activities. The antibacterial effect of the synthesized kanamycin derivatives declines or disappears as compared to the original kanamycin A. Several compounds, especially those with octyl chain at O-4″ and/or O-6″ positions on the ring III of kanamycin A, show very strong activity as antifungal agents. In addition, these compounds display no toxicity toward mammalian cells. Finally, computational calculation has revealed possible factors that are responsible for the observed regioselectivity. The simplicity in chemical synthesis and the fungal specific property make the lead compounds ideal candidates for the development of novel antifungal agents.

Comments

PubMed PMID: 27715046

Recommended Citation

Zhang, Q.; Alfindee, M.; Shrestha, J. P.; Nziko, V. P.; Kawasaki, Y.; Peng, X.; Takemoto, J. Y.; Chang, C.-W. T. “Divergent Synthesis of Three Classes of Antifungal Amphiphilic Kanamycin Derivatives.” J. Org. Chem. 2016, 81, 10651–10663. PubMed PMID: 27715046.