Design of Two Alternative Routes for the Synthesis of Naftifine and Analogues as Potential Antifungal Agents

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Rodrigo AboniaSusana Zacchino

Abstract

Two practical and efficient approaches have been implemented as alternative procedures for the synthesis of naftifine and novel diversely substituted analogues 16 and 20 in good to excellent yields, mediated by Mannich-type reactions as the key step of the processes. In these approaches, the γ-aminoalcohols 15 and 19 were obtained as the key intermediates and their subsequent dehydration catalyzed either by Brønsted acids like H₂SO₄ and HCl or Lewis acid like AlCl₃, respectively, led to naftifine, along with the target allylamines 16 and 20. The antifungal assay results showed that intermediates 18 (bearing both a β-aminoketo- and N-methyl functionalities in their structures) and products 20 were the most active. Particularly, structures 18b, 18c, and the allylamine 20c showed the lowest MIC values, in the 0.5-7.8 µg/mL range, against the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. Interesting enough, compound 18b bearing a 4-Br as the substituent of the phenyl ring, also displayed high activity against Candida albicans and Cryptococcus neoformans with MIC80 = 7.8 µg/mL, being fungicide rather than fungistatic with a relevant MFC value = 15.6 µg/mL against C. neoformans.

References

Jan 1, 1986·Journal of Medicinal Chemistry·A StützD Berney
Mar 23, 2002·Bioorganic & Medicinal Chemistry Letters·Felikss MutulisJarl E S Wikberg
May 6, 2005·Journal of Clinical Microbiology·M A PfallerD J Diekema
Feb 21, 2006·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·G Chamilos, D P Kontoyiannis
May 10, 2006·Bioorganic & Medicinal Chemistry·Nobutaka KitahataTadao Asami
Jan 16, 2007·Clinical Microbiology Reviews·M A Pfaller, D J Diekema
Jan 24, 2007·Bioorganic & Medicinal Chemistry·Nilo ZanattaMarcos A P Martins
Jun 6, 2009·Acta Crystallographica. Section C, Crystal Structure Communications·Juan C CastilloChristopher Glidewell
Feb 19, 2010·European Journal of Medicinal Chemistry·Alejandra GerpeHugo Cerecetto
Nov 15, 2014·Medical Mycology·Luana Pereira Borba-SantosSonia Rozental
Dec 15, 2015·Wiener klinische Wochenschrift·Arne-Wulf ScholtzGerhard Weisshaar

❮ Previous
Next ❯

Methods Mentioned

BETA
column chromatography

Software Mentioned

SigmaPlot

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Candida albicans

Candida albicans is an opportunistic, fungal pathogen of humans that frequently causes superficial infections of oral and vaginal mucosal surfaces of debilitated and susceptible individuals. Discover the latest research on Candida albicans here.

Candidiasis

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

Candidiasis (ASM)

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.