Synthesis and Antifungal Activity of Palmitic Acid-Based Neoglycolipids Related to Papulacandin D

Novel mannopyranoside esters as sterol 14α-demethylase inhibitors: Synthesis, PASS predication, molecular docking, and pharmacokinetic studies

“…Antimicrobial activities especially antifungal susceptibility of CFA esters is also related to CYP51 inhibition [ 19 , 22 ] similar to azoles, papulacandins etc. In addition, sugar moieties with ester groups as in papulacandins led to higher solubility and reduced hemolytic toxicity [ 36 ]. Hence, one of our major objectives was to get non-azole type MDM based potential CYP51 inhibitor to overcome MDR microbial strains.…”

Synthesis of novel papulacandin D analogs and evaluation of their antifungal potential

“…Both compounds were inactive at the highest concentration evaluated (500 µg.mL-1) against all fungal species. The absence of the rigid spiroketal moiety (the analogs are classical aryl glycosides and therefore more flexible) is expected to impair the biological activity of the compounds, albeit not essential as we have demonstrated in previous work (Souza et al, 2015) On the other hand, the side chain of the analogs is more rigid and less lipophilic than that of the prototype due to the presence of the aromatic rings and amide bond. It appears that the correct combination of molecular rigidity and lipophilic/ hydrophilic balance is essential for activity.…”

“…Glycosylation of 4-formyl-2-methoxyphenol with bromide 4 afforded the glucosyde 5 in 54% yield after purified by recrystallization, which upon deacetylation condition was converted into derivative 6 in 98% yield. Following the proposed synthetic route, the protection of O-4 and O-6 using benzaldehyde and ZnCl 2 afforded the acetal 7 in 72% yield (Souza et al, 2015). Compound 7 was coupled with previously synthesized carboxyl acid 14 using EDAC/DMAP to give a mixture of the desired compound 8 (obtained in 23% yield; Scheme 2) and the undesired 2,3-diester, which were separated by column chromatography.…”

“…In parallel, when the intermediary 7 reacted with carboxylic acid 15 under the same conditions described above for the preparation of 8, an inseparable mixture of desired derivative 9 (Scheme 2) and the undesired diester was obtained. The mixture was then treated with HCl to remove the 4,6-O-benzylidene protecting group and the crude mixture of the deprotected products was submitted to column chromatograpy (Souza et al, 2015). This procedure allowed us to isolate compound 2 in 22% yield.…”

“…Recently, our research group reported the synthesis and antifungal evaluation of papulacandin D analogs acylated at C-3 with palmitic acid. The low antifungal activity showed by these synthesized compounds can be explained by the absence of the spirocyclic nucleus or by the total saturation of the C-3 acyl chain (Souza et al, 2015). Therefore, based on antifungal potential of papulacandins combined with the lower structural complexity of Papulacandin D, we planned and synthesized new analogs of this compound employing the molecular simplification method and using a more complex acyl chain, containing unsaturations and different functional groups.…”