Preparation and antimalarial activity of a novel class of carbohydrate-derived, fused thiochromans

Kinfe, Henok H.; Moshapo, Paseka T.; Makolo, Felix L.; Gammon, David W.; Ehlers, Martin; Schmuck, Carsten

doi:10.1016/j.ejmech.2014.09.060

Cited by 21 publications

(23 citation statements)

References 22 publications

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“…Although replacing the sulfone with the sulfoximine indeed improved the antiplasmodial activity as anticipated, the activity was highly dependent on the absolute configuration of the sulfoximine stereogenic centre. In agreement with our previous report, [25] the activity of the sulfoximine derivatives was also dependent on the stereochemistry of the anomeric centre of the sugar moiety. With this finding in hand, we decided to convert the major sulfoximine 6a to its alkylated derivatives, thereby transforming it from being a hydrogen-bond donor to an T A B L E 1 Antiplasmodial and cytotoxicity assay of sulfone 5 and the sulfoximine derivatives a acceptor.…”

Section: Antiplasmodial Activitysupporting

confidence: 93%

“…[25,26] could be as a result of the set up used for the bioassay study. The difference between the current and our previously reported Ref.…”

Section: Conflict Of Interestmentioning

confidence: 99%

“…[25,26] Although compound 5 [25] (Figure 2) from the series of the tested compounds exhibited promising activity against both chloroquine-sensitive (3D7) and chloroquineresistant (FCR3) strains with IC 50 values of 0.3-0.4 μM, however, the inability of the sulfone functional group to undergo further diversification and manipulation limited the potential to explore the possibility of improving the IC 50 values of these scaffolds to nanomolar concentrations. [25,26] Although compound 5 [25] (Figure 2) from the series of the tested compounds exhibited promising activity against both chloroquine-sensitive (3D7) and chloroquineresistant (FCR3) strains with IC 50 values of 0.3-0.4 μM, however, the inability of the sulfone functional group to undergo further diversification and manipulation limited the potential to explore the possibility of improving the IC 50 values of these scaffolds to nanomolar concentrations.…”

Section: Introductionmentioning

confidence: 99%

“…[25] These limitations, coupled with the special features endowed to sulfoximines, prompted us to synthesize sulfoximine analogue 6 ( Figure 2) of the most active carbohydrate derived thiochroman 5, in the hope of improving the antiplasmodial activity of these scaffolds. [25] These limitations, coupled with the special features endowed to sulfoximines, prompted us to synthesize sulfoximine analogue 6 ( Figure 2) of the most active carbohydrate derived thiochroman 5, in the hope of improving the antiplasmodial activity of these scaffolds.…”

Section: Introductionmentioning

confidence: 99%

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Design, synthesis, and antiplasmodial evaluation of a series of novel sulfoximine analogues of carbohydrate‐based thiochromans

et al. 2018

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Sulfone/sulfoxide-containing carbohydrate derived thiochromans were found to be highly active antiplasmodial agents. However, the inability of the sulfone/sulfoxide functional groups for further derivatization and manipulation limited the potential for further exploration. In this study, based on the interesting and important physicochemical properties, as well as amenability of sulfoximines (isosters of sulfones) for further derivatization, a series of novel sulfoximine-type carbohydrate-derived thiochroman derivatives have been successfully synthesized, characterized, and evaluated for their antiplasmodial activity. Although the replacement of the sulfone functional group with a sulfoximine unit improved the antiplasmodial activity of the scaffolds, the activity was highly dependent on the configuration of the stereogenic centre at the sulfur atom. Moreover, analysis of the crystal structures of the sulfoximine analogues revealed that the bond between the sulfur and nitrogen atoms of the sulfoximine functional group is not a true double bond but rather a polarized single bond. K E Y W O R D Santimalarial, antiplasmodial, sulfoximine, thiochroman

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Section: Antiplasmodial Activitysupporting

confidence: 93%

“…[25,26] could be as a result of the set up used for the bioassay study. The difference between the current and our previously reported Ref.…”

Section: Conflict Of Interestmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Design, synthesis, and antiplasmodial evaluation of a series of novel sulfoximine analogues of carbohydrate‐based thiochromans

et al. 2018

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“…With our long standing on the chemical transformation of the thiochromans into important intermediates and biologically active compounds [16–19], it was noted that hemithioacetal 3 can be readily prepared from thiochroman 1 and we envisioned that a careful desulfurization could provide aryl- C -glucoside 4 with inherent 1,2- cis relationship between the easily transformable 2- C -branch and the aryl group at the C-2 and C-1 positions, respectively. Although detailed studies on the desulfurization of hemithioketals are well documented, the desulfurization of the related hemithioacetals (RCH(OH)SR) are less explored [20–21].…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals

Kinfe¹,

Mebrahtu²,

Manana³

et al. 2015

Beilstein J. Org. Chem.

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Summary1-C and 2-C-branched carbohydrates are present as substructures in a number of biologically important compounds. Although the synthesis of such carbohydrate derivatives is extensively studied, the synthesis of 1,2-cis-2-C-branched C-, S-, and N-glycosides is less explored. In this article a synthetic strategy for the synthesis of 1,2-cis-2-C-branched-aryl-C-glucosides is reported via a hydrogenolytic desulfurization of suitably orientated carbohydrate based hemithioacetals. 1,2-cis-2-Hydroxymethyl and 2-carbaldehyde of aryl-C-glucosides have been synthesized using the current strategy in very good yields. The 2-carbaldehyde-aryl-C-glucosides have been identified as suitable substrates for the stereospecific preparation of 2,3-unsaturated-aryl-C-glycosides (Ferrier products).

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Chemo‐ and Stereoselective Cytochrome P450‐BM3‐Catalyzed Sulfoxidation of 1‐Thiochroman‐4‐ones Enabled by Directed Evolution

2017

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Directed evolution utilizing an unconventional approach to saturation mutagenesis has been applied to cytochrome P450-BM3 as ac atalyst in the asymmetric sulfoxidationo f1 -thiochroman-4-one andt wo derivatives thereof with complete chemoselectivity as wella s( S)-and (R)-selectivity on an optionalb asis.W hereas wild-type P450-BM3 shows in the case of the parent compound poor enantioselectivity in slight favor of the (S)-sulfoxide (er = 75:25), (S)-selectivity was enhancedt oer = 93:7,w hile reversal of enantioselectivity favoring the (R)-sulfoxide was also achieved (er = 7:93). Tw o derivatives of the parent substrate underwent similar stereoselective sulfoxidationr eactions.S ulfoxides of this type are of potential pharmaceutical interest. This biocatalytic approach nicely complements synthetic methods.Keywords: asymmetric sulfoxidation; directede volution;P 450 monooxygenase;s aturation mutagenesis;sulfoxidation; thiochroman-4-one sulfoxides An umber of biologicallya ctive compoundsc ontain as building blocks chiral sulfoxideso ft he type 2 prepared from thiochromanone-4-one derivatives 1 (Scheme1). [1] Reagents such as dimethyldioxirane lead to racemateso f2a, [1] as do achiral catalysts such as Ni complexes [2] under Mukaiyama conditions [3] employinga na ldehyde in the presence of O 2 with intermediatef ormationo ft he actual oxidant RCO 3 H. The applicationo fc hiral transitionm etal catalysts has been attempted several times, [4] the best results are achieved with an Al-complex as catalyst and hydrogen peroxidea so xidant, leading to 97% ee in the formation of (S)-2a. [4a] In other work, thiochromanderivatives of glucose were subjectedt oo xidation by cerium ammonium nitrate with formation of 2:1d iastereomeric mixtures of sulfoxides. [5] We were interested in as tereoselective biocatalytic procedure using atmospheric oxygen as am ild oxidant. To the best of our knowledge,t his approachh as not been reported to date.T he asymmetric sulfoxidation of the parent compound 1a was reported to be catalyzed by the chloroperoxidase from Caldariomyces fumago with formation of (R)-2a (95% ee), but this procedure utilizes at wo-fold excesso fh ydrogen peroxidea so xidant. [6] Moreover, the enantiomeric product (S)-2a could not be accessed. Previously,t his enzyme had been used in the oxidation of other prochiral thioethers andav ariety of other compounds,l ikewise based on hydrogen peroxide. [7] CytochromeP 450 monooxygenases (CYPs) catalyze ar emarkable range of oxidative reactiont ypes with oxygenf rom the air as oxidant, including CH-activatingh ydroxylation, olefin epoxidation, sulfoxidaScheme1.Cytochrome P450-BM3-catalyzed asymmetric sulfoxidation of 1-thiochroman-4-one and derivatives.

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Preparation and antimalarial activity of a novel class of carbohydrate-derived, fused thiochromans

Cited by 21 publications

References 22 publications

Design, synthesis, and antiplasmodial evaluation of a series of novel sulfoximine analogues of carbohydrate‐based thiochromans

Design, synthesis, and antiplasmodial evaluation of a series of novel sulfoximine analogues of carbohydrate‐based thiochromans

Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals

Chemo‐ and Stereoselective Cytochrome P450‐BM3‐Catalyzed Sulfoxidation of 1‐Thiochroman‐4‐ones Enabled by Directed Evolution

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