Anti-protozoal and anti-fungal evaluation of 3,5-disubstituted 1,2-dioxolanes

Abstract

Endoperoxides are a class of compounds, which is well-known for their antimalarial properties, notably, but few reports exist about 3,5-disubstituted 1,2-dioxolanes. After having designed a new synthetic route for the preparation of these substances, they were evaluated against 4 different agents of infectious diseases, protozoa (Plasmodium, Leishmania) and Fungi (Candida and Aspergillus). Whereas moderate antifungal activity was found for our products, potent antimalarial and antileishmanial activities were observed for a few compounds. The nature of the substituents linked to the endoperoxide ring seems to play an important role in the bioactivities.

Organocatalytic Asymmetric Peroxidation of γ,δ-Unsaturated β-Keto Esters—A Novel Route to Chiral Cycloperoxides

“…An ion of mass 211.0934 was detected by HRMS, which corresponds to the sodium adduct of 86. Additionally, the chemical shifts of the C-3 peaks at 81.9 ppm and 82.5 ppm and the C-4 peaks at 44.9 ppm and 45.4 ppm are similar to those reported for comparable dioxolanes in the literature [59][60][61][62]. The cis-and trans-isomers may be differentiated by the distinct chemical shifts of the H-4 protons which appear at 1.89 ppm and 2.88 ppm in cis-86 due to their differing chemical environments (Figure 2).…”

Lewis Acids and Heteropoly Acids in the Synthesis of Organic Peroxides

“…The use of catalytic amounts of Sc(OTf) 3 or InCl 3 in the reaction of endoperoxyacetals 101 with allyltrimethylsilane (AllylTMS) and its derivatives (Nu-TMS) makes it possible to obtain 3,5-disubstituted-1,2-dioxolanes 102 and 103 by the Sakurai reaction. Sc(OTf) 3 or InCl 3 allow the reaction to be carried out under milder conditions than when using SnCl 4 and TiCl 4 (Scheme 36) [128,129]. The use of catalytic amounts of Sc(OTf)3 or InCl3 in the reaction of endoperoxyacetals 101 with allyltrimethylsilane (AllylTMS) and its derivatives (Nu-TMS) makes it possible to obtain 3,5-disubstituted-1,2-dioxolanes 102 and 103 by the Sakurai reaction.…”

“…The use of catalytic amounts of Sc(OTf)3 or InCl3 in the reaction of endoperoxyacetals 101 with allyltrimethylsilane (AllylTMS) and its derivatives (Nu-TMS) makes it possible to obtain 3,5-disubstituted-1,2-dioxolanes 102 and 103 by the Sakurai reaction. Sc(OTf)3 or InCl3 allow the reaction to be carried out under milder conditions than when using SnCl4 and TiCl4 (Scheme 36) [128,129]. Cyclic peroxides such as spiro 1,2,4-trioxepanes 106 were obtained from hydroperoxides 104 and ketones 105 by using Indium (III) triflate as a catalyst (Scheme 37) [130].…”

“…In 2002, Dussault et al [127] demonstrated the ring opening of oxetanes 95 with an ethereal solution of H 2 O 2 , catalyzed by Yb(OTf) 3 and Sc(OTf) 3 with the formation of peroxides 96, which act as intermediates in the synthesis 1,2,4-trioxepanes 97 (Scheme 34).Hydroperoxyoxetane 98 rearranged into endoperoxide 99 in 12% yield and exoperoxide 100 in 33% yield under the action of Yb(OTf) 3 in methylene chloride (Scheme 35)[74].The use of catalytic amounts of Sc(OTf) 3 or InCl 3 in the reaction of endoperoxyacetals 101 with allyltrimethylsilane (AllylTMS) and its derivatives (Nu-TMS) makes it possible to obtain 3,5-disubstituted-1,2-dioxolanes 102 and 103 by the Sakurai reaction. Sc(OTf) 3 or InCl 3 allow the reaction to be carried out under milder conditions than when using SnCl 4 and TiCl 4 (Scheme 36)[128,129].…”