Sulfonyloxy Groups Research Articles

Synthesis of novel 18β-glycyrrhetinic acid sulfonate derivatives displaying significant anti-oomycete activity against Phytophthora capsici

Using 18β-glycyrrhetinic acid (GA) as the lead compound, fourteen GA sulphonate derivatives (3a–n) were prepared by modifying its C-3 OH group, and their structures were well confirmed by 1H NMR, 13C NMR, HRMS and melting points. Moreover, we screened the anti-oomycete activity of these compounds against Phytophthora capsici by using the mycelial growth rate method. Among the fourteen GA sulphonate derivatives evaluated, four compounds 3f, 3j, 3k and 3l exhibited more potent anti-oomycete activity than that of the positive control zoxamide (EC50 = 25.17 mg/L), and had the median effective concentration (EC50) values of 23.04, 16.16, 22.55, and 13.93 mg/L, respectively. Especially compound 3l showed the best anti-oomycete activity against P. capsici with EC50 value of 13.93 mg/L. Overall, the introduction of sulfonyloxy groups at the C-3 position of GA has a significant impact on its anti-oomycete activity, and the corresponding derivative activity varies significantly with different substituents R.

Synthesis, anti-oomycete and fungal activities of resveratrol sulfonate derivatives containing three esters moieties

In order to explore novel natural product-based anti-oomycete and fungal agents, thirteen unreported resveratrol sulfonate derivatives containing three esters moieties were designed and prepared using the principle of activity superposition, and structurally confirmed by 1H NMR, 13C NMR, HRMS, and m.p. Furthermore, we evaluated the target compounds (3a–m) as anti-oomycete and fungal activities against two serious agricultural diseases of Phytophthora capsici and Fusarium graminearum, respectively. Among the thirteen resveratrol sulfonate derivatives tested, three compounds 3d, 3k, and 3l exhibited the most potent anti-oomycete activity against P. capsici with EC50 values of 27.31, 27.69, and 26.14 mg/L, respectively. Moreover, two compounds 3e and 3l exhibited the most potent anti-fungal activity against F. graminearum with EC50 values of 75.81, and 73.60 mg/L, respectively. Overall, the anti-oomycete activity against P. capsici of the target compound was significantly better than that of the anti-fungal activity against F. graminearum. In particular, anti-oomycete and fungal activities showed that the structural skeleton presentation activity was closely related to the different substituents of the sulfonyloxy groups, especially the anti-oomycete activity. This study will lay a solid foundation for further modifying resveratrol to develop potential new fungicides.

Combinatorial Synthesis of Novel 1-sulfonyloxy/acyloxyeugenol Derivatives as Fungicidal Agents.

Developing the high-efficiency and low-risk small-molecule greenfungicide is the key to effective control of the plant pathogenic oomycetes. Essential oils play a very important role in novel fungicide discovery for their unique sources and potential target sites. Eugenol, a kind of plant essential oil, was mainly isolated from the unopened and dried flower buds of Syzygium aromaticum of the Myrtaceae family. Due to its unique structural skeleton, eugenol and its derivatives have exhibited a wide range of biological activities. However, a study on the synthesis of novel 1-sulfonyloxy/acyloxyeugenol derivatives as fungicidal agents against Phytophthora capsici has not yet been reported. Twenty-six novel 1-sulfonyloxy/acyloxyeugenol derivatives (3a-p and 5a-j) were prepared and their structures were well characterized by 1H NMR, HRMS, and m.p. Their fungicidal activity was evaluated against P. capsici by using the mycelial growth rate method. To find novel natural-product-based fungicidal agents to control the plant pathogenic oomycetes, we herein designed and synthesized two series of novel 1-sulfonyloxy/acyloxyeugenol derivatives (3a-p and 5a-j) as fungicidal agents against P. capsici Leonian, in vitro. Results of fungicidal activity revealed that, among all compounds, especially compounds 3a, 3f, and 3n displayed the most potent anti-oomycete activity against P. capsici with EC50 values of 79.05, 75.05, and 70.80, respectively. The results revealed that the anti-oomycete activity of eugenol with the sulfonyloxy group was higher than that with the acyloxy group. It is suggested that the fungicidal activity of eugenol can be improved by introducing the sulfonyloxy group. This will pave the way for further design, structural modification, and development of eugenol derivatives as fungicidal agents.

Analysis of FR901379 Biosynthetic Genes in Coleophoma empetri by Clustered Regularly Interspaced Short Palindromic Repeats/Cas9-Based Genomic Manipulation.

The compound FR901379, a sulfated echinocandin produced by the filamentous fungus Coleophoma empetri F-11899, is an important intermediate for the synthesis of the antifungal drug micafungin. In this study, we established an efficient clustered regularly interspaced short palindromic repeats/Cas9-based gene editing tool for the industrial production strain C. empetri SIPI1284. With this method, the efficiency of gene mutagenesis in the target locus is up to 84%, which enables the rapid gene disruption for the analysis of FR901379 biosynthetic genes. Next, we verified the putative functional genes of the FR901379 biosynthetic gene cluster via gene disruption and gene complementation in vivo. These core functional genes included the nonribosomal peptide synthetase gene (CEnrps), the fatty-acyl-AMP ligase gene (CEligase) responsible for the formation of the activated form of palmitic acid and its transfer to CEnrps, four nonheme mononuclear iron oxygenase genes (CEoxy1, CEoxy2, CEoxy3, and CEoxy4) responsible for the synthesis of nonproteinogenic amino acids, l-homotyrosine biosynthesis genes (CEhtyA-D), two cytochrome P450 enzyme genes (CEp450-1 and CEp450-2), and a transcription regulator gene (CEhyp). In addition, by screening the whole genome, we identified two unknown genes (CEp450-3 and CEsul) responsible for the sulfonyloxy group of FR901379, which were separated from the core FR901379 biosynthetic cluster. Furthermore, during gene disruptions in the research, we obtained a series of FR901379 analogues and elucidated the relationship between the groups and antifungal activities.

Effect of noncovalent interactions in ion pairs on hypervalent iodines: inversion of regioselectivity in sulfonyloxylactonization

The noncovalent interactions between the sulfonyloxy group and the cationic nitrogen-containing heterocyclic moiety substituted in hypervalent iodines caused specific regioselectivity in the sulfonyloxylactonization of 2-vinyl benzoic acids.

Synthesis of sulfonyloxy furoxans via hydroxyfuroxan ammonium salts

Furoxans are distinctive heteroaromatic compounds in that they are potentially capable of releasing nitric oxide under physiological conditions. In order to utilize the furoxan scaffold for the development of functional molecules, synthetically relevant functional groups are required for access to diverse furoxans. In this report, a facile route to furoxans with sulfonyloxy groups, which are halide surrogates, has been developed. The key features of this strategy include the synthesis and utilization of bench-stable hydroxyfuroxan salts, the use of sulfonyl anhydrides in the sulfonylation step instead of sulfonyl chlorides, and the photochemical isomerization of one regioisomer to another in order to gain access to both.

ChemInform Abstract: Diverse sp3 C—H Functionalization Through Alcohol β‐Sulfonyloxylation.

AbstractA strategy for the selective introduction of sulfonyloxy groups into unactivated β‐C—H bonds of masked alcohols is described.

Diverse sp(3) C-H functionalization through alcohol β-sulfonyloxylation.

Site-selective C-H functionalization has emerged as an attractive tool for derivatizing complex synthetic intermediates, but its use for late-stage diversification is limited by the functional groups that can be introduced, especially at unactivated sp(3)-hybridized positions. To overcome this, we introduce a strategy that directly installs a sulfonyloxy group at a β-C-H bond of a masked alcohol and subsequently employs nucleophilic substitution reactions to prepare various derivatives. Hydroxyl groups are widely found in bioactive molecules and are thus readily available as synthetic handles. A directing group is easily added (and subsequently removed) from the alcohols such that a formal site-selective β-C-H sulfonyloxylation of these alcohols is achieved. Substitution reactions with carbon, nitrogen, oxygen and other nucleophiles then lead to diverse functionalizations that may help to streamline the synthesis of complex analogues for drug discovery.

Редокс превращения и нуклеофильные замещения как возможные метаболические реакции препарата «Триазавирина». Химическое моделирование процессов метаболизма

As a model of metabolic transformations of antiviral drug “Triazaverin” and its analogues‑2-alkylthio‑6-nitro‑1,2,4-triazolo[5,1-c][1,2,4]triazine‑7-ones 1a-d examined the oxidation of alkylthio groups to the corresponding sulfoxides 2a-d and sulfones 3a-d, as well as the process of nucleophilic substitution sulfonyloxy group of cysteine and cysteamine with the formation of compounds 5 and 6.

ChemInform Abstract: An Improved Synthesis of 2,3- and 3,4-Unsaturated Pyranosides: The Use of Microwave Energy.

Tipson-Cohen reactions of sugar derivatives containing contiguous sulfonyloxy groups have been studied in a microwave oven. Considerable rate increases and high yields of the unsaturated products have been observed.

1-(4-Chlorophenyl)cyclopropyl](piperazin-1-yl)methanone

The title compound, [1-(4-chlorophenyl)cyclopropyl](piperazin-1-yl)methanone, was synthesized and characterized by elemental analysis, IR, 1H NMR, 13C NMR and mass spectral data.

O-Arylsulfonyl hydroxylamines via a decarboxylative rearrangement

( E)- O-Arylsulfonyl- N-(2-nitroalk-2-enyl)hydroxylamines were easily obtained in good yields starting from ( E)-nitro allylic alcohols, the crucial step being an inorganic base-catalyzed decarboxylative rearrangement of proposed labile unsaturated carbamates. A possible mechanism for the outcome of the reaction, characterized by the unusual retention of the sulfonyloxy group, is proposed.

Structure Proof and Synthesis of Kotalanol and De-O-sulfonated Kotalanol, Glycosidase Inhibitors Isolated from an Herbal Remedy for the Treatment of Type-2 Diabetes

Kotalanol and de-O-sulfonated-kotalanol are the most active principles in the aqueous extracts of Salacia reticulata which are traditionally used in India, Sri Lanka, and Thailand for the treatment of diabetes. We report here the exact stereochemical structures of these two compounds by synthesis and comparison of their physical data to those of the corresponding natural compounds. The candidate structures were based on our recent report on the synthesis of analogues and also the structure-activity relationship studies of lower homologues. The initial synthetic strategy relied on the selective nucleophilic attack of p-methoxybenzyl (PMB)-protected 4-thio-D-arabinitol at the least hindered carbon atom of two different, selectively protected 1,3-cyclic sulfates to afford the sulfonium sulfates. The protecting groups consisted of a methylene acetal, in the form of a seven-membered ring, and benzyl ethers. Deprotection of the adducts yielded the sulfonium ions but also resulted in de-O-sulfonation. Comparison of the physical data of the two adducts to those reported for de-O-sulfonated natural kotalanol yielded the elusive structure of kotalanol by inference. The side chain of this compound was determined to be another naturally occurring heptitol, d-perseitol (d-glycero-d-galacto-heptitol) with a sulfonyloxy group at the C-5 position. The synthesis of kotalanol itself was then achieved by coupling PMB-protected 4-thio-d-arabinitol with a cyclic sulfate that was synthesized from the naturally occurring d-perseitol. The work establishes unambiguously the structures of two natural products, namely, kotalanol and de-O-sulfonated kotalanol.

Regio- and stereocontrolled synthesis of novel 3-sulfonamido-2,3,4,5-tetrahydro-1,5-benzothiazepines from 2-(bromomethyl)- or 2-(sulfonyloxymethyl)aziridines

2-(Bromomethyl)-1-sulfonylaziridines were converted into novel 3-sulfonamido-2,3,4,5-tetrahydro-1,5-benzothiazepines upon treatment with 2-aminothiophenol in THF in the presence of K2CO3. Starting from 3-substituted 2-(sulfonyloxymethyl)aziridines, a regio- and stereocontrolled synthesis of trans-2-phenyl- and trans-4-(phenyl or propyl)-3-sulfonamido-2,3,4,5-tetrahydro-1,5-benzothiazepines was developed in good yields via two different reaction pathways, depending on the nature of the sulfonyloxy group.

Sulfonate chalcone as new class voltage-dependent K+ channel blocker

Chalcone derivatives 1-17 were synthesized and their voltage-dependent K+ channel inhibitory activities were investigated. The effective K+ channel blockers were shown to be sulfonate chalcones 9-17, in which the sulfonyloxy group is placed on the A-ring. The 3'-(p-aminobenzene-sulfonylhydroxy)-4-hydroxychalcone 17 (IC50 = 0.51+/-0.05 microM) was the most potent K+ channel blocker.

Mechanistically diverse copper-, silver-, and gold-catalyzed acyloxy and phosphatyloxy migrations: efficient synthesis of heterocycles via cascade migration/cycloisomerization approach.

A set of cycloisomerization methodologies of alkynyl ketones and imines with concurrent acyloxy, phosphatyloxy, or sulfonyloxy group migration, which allow for the efficient synthesis of multisubstituted furans and N-fused heterocycles, has been developed. Investigation of the reaction course by way of employing 17O-labeled substrates allowed for elucidation of the mechanisms behind these diverse transformations. It was found that, while the phosphatyloxy migration in conjugated alkynyl imines in their cycloisomerization to N-fused pyrroles proceeded via a [3,3]-sigmatropic rearrangement, the analogous cycloisomerization of skipped alkynyl ketones proceeds through two consecutive 1,2-migrations, resulting in an apparent 1,3-shift, followed by a subsequent 1,2-migration through competitive oxirenium and dioxolenylium pathways. Investigations of the 1,2-acyloxy migration of conjugated alkynyl ketones en route to furans demonstrated the involvement of a dioxolenylium intermediate. The mechanism of cycloisomerization of skipped alkynyl ketones containing an acyloxy group was found to be catalyst dependent; Lewis and Brønsted acid catalysts caused an ionization/SN1' isomerization to the allene, followed by cycloisomerization to the furan, whereas transition metal catalysts evoked a Rautenstrauch-type mechanistic pathway. Furthermore, control experiments in the cycloisomerization of skipped alkynyl ketones under transition metal catalysis revealed that, indeed, these reactions were catalyzed by transition metal complexes as opposed to Brønsted acids resulting from hydrolysis of these catalysts with eventual water. Further synthetic utility of the obtained phosphatyloxy-substituted heterocycles was demonstrated through their efficient employment in the Kumada cross-coupling reaction with various Grignard reagents.

A Novel 1,2‐Migration of Acyloxy, Phosphatyloxy, and Sulfonyloxy Groups in Allenes: Efficient Synthesis of Tri‐ and Tetrasubstituted Furans.

ChemInformVolume 35, Issue 32 Heterocyclic Compounds A Novel 1,2-Migration of Acyloxy, Phosphatyloxy, and Sulfonyloxy Groups in Allenes: Efficient Synthesis of Tri- and Tetrasubstituted Furans. Anna W. Sromek, Anna W. Sromek Dep. Chem., Univ. Ill., Chicago, IL 60607, USASearch for more papers by this authorAlexander V. Kel'in, Alexander V. Kel'in Dep. Chem., Univ. Ill., Chicago, IL 60607, USASearch for more papers by this authorVladimir Gevorgyan, Vladimir Gevorgyan Dep. Chem., Univ. Ill., Chicago, IL 60607, USASearch for more papers by this author Anna W. Sromek, Anna W. Sromek Dep. Chem., Univ. Ill., Chicago, IL 60607, USASearch for more papers by this authorAlexander V. Kel'in, Alexander V. Kel'in Dep. Chem., Univ. Ill., Chicago, IL 60607, USASearch for more papers by this authorVladimir Gevorgyan, Vladimir Gevorgyan Dep. Chem., Univ. Ill., Chicago, IL 60607, USASearch for more papers by this author First published: 20 July 2004 https://doi.org/10.1002/chin.200432125Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume35, Issue32August 10, 2004 RelatedInformation

Synthesis and evaluation of glycosidase inhibitory activity of octahydro-2 H-pyrido[1,2- a]pyrimidine and octahydro-imidazo[1,2- a]pyridine bicyclic diazasugars

An efficient chiron approach for the synthesis of bicyclic diazasugars 4a and 4b having both –CH 2OH and –OH functionality at the same carbon atom (C-6) is reported. Thus, easily available α- d-xylo-pentodialdo-1,4-furanose 5, obtained from d-glucose, on aldol-crossed Cannizzaro reaction followed by hydrogenolysis afforded 7. The regio-selective β- and α-sulfonylation of hydroxymethyl groups in 7 afforded 8a (β-sulfonylation) and 11 (α-sulfonylation) in good yields. The cleavage of the 1,2-acetonide functionality, individually in 8a and 11, followed by reaction with ethylenediamine gave in situ formation of sugar aminals that undergo concomitant nucleophilic displacement of the sulfonyloxy group, by amino functionality, to give hitherto unknown bicyclic diazasugars 4a and 4b, respectively. The inhibitory potency of the earlier reported bicyclic diazasugars 3a, b and 4a, b was evaluated against α- and β-glycosidases and they were found to be potent and specific against the β-glycosidases with IC 50 and K i values in the micro molar range.

A novel 1,2-migration of acyloxy, phosphatyloxy, and sulfonyloxy groups in allenes: efficient synthesis of tri- and tetrasubstituted furans.

Heading south: The 1,2-migration of the acyloxy, phosphatyloxy, and sulfonyloxy groups in allenyl systems has been discovered. This migration, combined with the transition-metal-catalyzed cycloisomerization reaction, leads to the efficient synthesis of tri- and tetrasubstituted acyl-, phosphatyl-, and sulfonyloxy-substituted furans as single regioisomers. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z53535_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

A Novel 1,2‐Migration of Acyloxy, Phosphatyloxy, and Sulfonyloxy Groups in Allenes: Efficient Synthesis of Tri‐ and Tetrasubstituted Furans

A Novel 1,2‐Migration of Acyloxy, Phosphatyloxy, and Sulfonyloxy Groups in Allenes: Efficient Synthesis of Tri‐ and Tetrasubstituted Furans