Gram-scale approach for ß-costic acid via allylic oxidation of ß-selinene.

ß-Costic acid is a sesquiterpene phytoalexin with acaricidal activity against Varroa destructor and antitrypanosomal activity. A concise and efficient method was developed for the synthesis of ß-costic acid via the allylic oxidation of ß-selinene, a component of celery seed oil.

Deciphering the Antibiofilm, Antibacterial, and Antioxidant Potential of Essential Oil from Indian Garlic and its Phytocompounds Against Foodborne Pathogens.

Garlic (Allium sativum L.), particularly its volatile essential oil, is widely recognized for medicinal properties. We have evaluated the efficacy of Indian Garlic Essential Oil (GEO) for antimicrobial and antibiofilm activity and its bioactive constituents. Allyl sulfur-rich compounds were identified as predominant phytochemicals in GEO, constituting 96.51% of total volatile oils, with 38% Diallyl trisulphide (DTS) as most abundant. GEO exhibited significant antibacterial activity against eleven bacteria, including three drug-resistant strains with minimum inhibitory concentrations (MICs) ranging from 78 to 1250 µg/mL. In bacterial growth kinetic assay GEO effectively inhibited growth of all tested strains at its ½ MIC. Antibiofilm activity was evident against two important human pathogens, S. aureus and P. aeruginosa. Mechanistic studies demonstrated that GEO disrupts bacterial cell membranes, leading to the release of nucleic acids, proteins, and reactive oxygen species. Additionally, GEO demonstrated potent antioxidant activity at IC50 31.18 mg/mL, while its isolated constituents, Diallyl disulphide (DDS) and Diallyl trisulphide (DTS), showed effective antibacterial activity ranging from 125 to 500 µg/mL and 250-1000 µg/mL respectively. Overall, GEO displayed promising antimicrobial and antibiofilm activity against enteric bacteria, suggesting its potential application in the food industry.

Industrial Distillation Fractions of Garlic Essential Oil, Design, Synthesis, and Antifungal Activity Evaluation of Aliphatic Substituted Trisulfide Derivatives.

Garlic oil has a wide range of biological activities, and its broad-spectrum activity against phytopathogenic fungi still has the potential to be explored. In this study, enzymatic treatment of garlic resulted in an increase of approximately 50 % in the yield of essential oil, a feasible GC-MS analytical program for garlic oil was provided. Vacuum fractionation of the volatile oil and determination of its inhibitory activity against 10 fungi demonstrated that garlic oil has good antifungal activity. The antifungal activity levels were ranked as diallyl trisulfide (S-3)>diallyl disulfide (S-2)>diallyl monosulfide (S-1), with an EC50 value of S-3 against Botrytis cinerea reached 8.16 mg/L. Following the structural modification of compound S-3, a series of derivatives, including compounds S-4~7, were synthesized and screened for their antifungal activity. The findings unequivocally demonstrated that the compound dimethyl trisulfide (S-4) exhibited exceptional antifungal activity. The EC50 of S-4 against Sclerotinia sclerotiorum reached 6.83 mg/L. SEM, In vivo experiments, and changes in mycelial nucleic acids, soluble proteins and soluble sugar leakage further confirmed its antifungal activity. The study indicated that the trisulfide bond structure was the key to good antifungal activity, which can be developed into a new type of green plant-derived fungicide for plant protection.

Which Constituents Determine the Antioxidant Activity and Cytotoxicity of Garlic? Role of Organosulfur Compounds and Phenolics.

Garlic is a vegetable with numerous pro-health properties, showing high antioxidant capacity, and cytotoxicity for various malignant cells. The inhibition of cell proliferation by garlic is mainly attributed to the organosulfur compounds (OSCs), but it is far from obvious which constituents of garlic indeed participate in the antioxidant and cytotoxic action of garlic extracts. This study aimed to obtain insight into this question by examining the antioxidant activity and cytotoxicity of six OSCs and five phenolics present in garlic. Three common assays of antioxidant activity were employed (ABTS● decolorization, DPPH● decolorization, and FRAP). Cytotoxicity of both classes of compounds to PEO1 and SKOV-3 ovarian cancer cells, and MRC-5 fibroblasts was compared. Negligible antioxidant activities of the studied OSCs (alliin, allicin, S-allyl-D-cysteine, allyl sulfide, diallyl disulfide, and diallyl trisulfide) were observed, excluding the possibility of any significant contribution of these compounds to the total antioxidant capacity (TAC) of garlic extracts estimated by the commonly used reductive assays. Comparable cytotoxic activities of OSCs and phenolics (caffeic, p-coumaric, ferulic, gallic acids, and quercetin) indicate that both classes of compounds may contribute to the cytotoxic action of garlic.

Quaternization-based graft modification of straw fibers for conditioning the sludge dewatering performance.

Extracellular polymeric substances (EPS) are a critical influencing factor in sludge dewatering. Disrupting such EPS contributes to the release of bound water in sludge, enhancing the sludge dewatering performance. In This study, quaternized straw fibers that are destructive to the EPS structure and components in active sludge were prepared useing heterogeneous free radical graft polymerization. Straw fibers, dimethyl diallyl ammonium chloride (DMDAAC), ammonium persulfate (APS), and acrylamide (AM) were taken as the substrate, grafting monomer, catalyst, and cross-linking agent, respectively.The optimal processing conditions determined for the DMDAAC-based quaternization and graft modification of straw fibers were as follows: reaction temperature of 60 °C, reaction time of 5 h, 0.100 g of catalyst APS dosage per gram of straw, and 3.000 ml of DMDAAC dosage per gram of straw. The optimal processing conditions yielded 1.335 g of modified straw fibers per gram of straw, 33.67% grafting rate, and 31.70% substitution of the quaternary ammonium groups. The capillary suction time (CST) was conditioned from 243.3 ± 22.6 s in the original sludge to 134.5 ± 34.45 s. The specific resistance to filtration (SRF) was reduced from 8.82 ± 0.51 × 1012 m/kg in the original sludge to 4.59 ± 0.23 × 1012 m/kg.

Sulfide-Directed Ir-Catalyzed Vinylic sp2 and Benzylic sp3 †C-H Activation for the Construction of Sulfur-Containing Medium-Ring System.

Ir-catalyzed transformations initiated by sulfur-directed vinylic sp2 and benzylic sp3  C-H activation are disclosed that achieve the construction of sulfur-containing seven- and eight-membered systems. Allyl 2-alkynylphenyl sulfides were transformed into dihydrobenzothiepines in 30-95 % yield, and 2-alkynylaryl 2-tolyl sulfides were converted into dibenzo[b,f]thiepines in 57-95 % yield along with double bond isomerization. In both reactions, the combination of Ir catalyst and sulfide moiety was a key to the facile cyclization.

Palladium-Catalyzed Branch- and Z-Selective Allylic C-H Amination with Aromatic Amines.

Allylamines are important building blocks in the synthesis of bioactive compounds. The direct coupling of allylic C-H bonds and commonly available amines is a major synthetic challenge. An allylic C-H amination of 1,4-dienes has been accomplished by palladium catalysis. With aromatic amines, branch-selective allylic aminations are favored to generate thermodynamically unstable Z-allylamines. In addition, more basic aliphatic cyclic amines can also engage in the reaction, but linear dienyl allylic amines are the major products.

Enantioselective and Diastereodivergent Allylation of Propargylic C-H Bonds.

An iridium-catalyzed stereoselective coupling of allylic ethers and alkynes to generate 3,4-substituted 1,5-enynes is reported. Under optimized conditions, the coupling products are formed with excellent regio-, diastereo-, and enantioselectivities, and the protocol is functional group tolerant. Moreover, we report conditions that allow the reaction to proceed with complete reversal of diastereoselectivity. Mechanistic studies are consistent with an unprecedented dual role for the iridium catalyst, enabling the propargylic deprotonation of the alkyne through π-coordination, as well as the generation of a π-allyl species from the allylic ether starting material.

Metal-Free Regioselective Hydrophosphorodithioation of Spirovinylcyclopropyl Oxindoles: Rapid Access to Allyl Dialkylphosphorodithioates.

Phosphorodithioates are important substructures due to their great use in bioactive compounds and functional materials. A metal-free 1,5-addition of spirovinylcyclopropyl oxindoles have been developed by choosing P4S10 and alcohol as nucleophiles through the regioselective ring-opening of spirovinylcyclopropyl oxindoles. This method provides access to allylic organothiophosphates with high efficiency, wide functional group tolerance, good chemo- and regioselectivity, and E-selectivity. 1,3-Addition products were also prepared in high yield. Furthermore, the resulting organothiophosphates could be readily transformed into other allylic derivatives.

Highly diastereo- and enantioselective synthesis of multisubstituted allylic amino acid derivatives by allylic alkylation of a chiral glycine-based nickel complex and vinylethylene carbonates.

The asymmetric synthesis of multisubstituted allylic amino acid derivatives was accomplished by the allylic alkylation of a chiral glycine-based nickel complex with vinylethylene carbonates. High enantioselectivities and diastereoselectivities were obtained under mild reaction conditions. The gram-scale synthesis was carried out with a good yield and high enantioselectivity, indicating that the method is a highly efficient route to chiral multisubstituted allylic amino acid derivatives.

Reactions of Allylmagnesium Reagents with Carbonyl Compounds and Compounds with C═N Double Bonds: Their Diastereoselectivities Generally Cannot Be Analyzed Using the Felkin-Anh and Chelation-Control Models.

This review describes the additions of allylmagnesium reagents to carbonyl compounds and to imines, focusing on the differences in reactivity between allylmagnesium halides and other Grignard reagents. In many cases, allylmagnesium reagents either react with low stereoselectivity when other Grignard reagents react with high selectivity, or allylmagnesium reagents react with the opposite stereoselectivity. This review collects hundreds of examples, discusses the origins of stereoselectivities or the lack of stereoselectivity, and evaluates why selectivity may not occur and when it will likely occur.

Scalable and sustainable electrochemical allylic C-H oxidation.

New methods and strategies for the direct functionalization of C-H bonds are beginning to reshape the field of retrosynthetic analysis, affecting the synthesis of natural products, medicines and materials. The oxidation of allylic systems has played a prominent role in this context as possibly the most widely applied C-H functionalization, owing to the utility of enones and allylic alcohols as versatile intermediates, and their prevalence in natural and unnatural materials. Allylic oxidations have featured in hundreds of syntheses, including some natural product syntheses regarded as "classics". Despite many attempts to improve the efficiency and practicality of this transformation, the majority of conditions still use highly toxic reagents (based around toxic elements such as chromium or selenium) or expensive catalysts (such as palladium or rhodium). These requirements are problematic in industrial settings; currently, no scalable and sustainable solution to allylic oxidation exists. This oxidation strategy is therefore rarely used for large-scale synthetic applications, limiting the adoption of this retrosynthetic strategy by industrial scientists. Here we describe an electrochemical C-H oxidation strategy that exhibits broad substrate scope, operational simplicity and high chemoselectivity. It uses inexpensive and readily available materials, and represents a scalable allylic C-H oxidation (demonstrated on 100 grams), enabling the adoption of this C-H oxidation strategy in large-scale industrial settings without substantial environmental impact.

Cooperative Catalyst-Enabled Regio- and Stereodivergent Synthesis of α-Quaternary α-Amino Acids via Asymmetric Allylic Alkylation of Aldimine Esters with Racemic Allylic Alcohols.

We describe cooperative bimetallic catalysis that enables regio-/stereodivergent asymmetric α-allylations of aldimine esters. By employing Et3 B as the key activator, racemic allylic alcohols can be directly ionized to form Pd or Ir-π-allyl species in the presence of achiral Pd or chiral Ir complexes, respectively. The less or more substituted allylic termini of the metal-π-allyl species are amenable to nucleophilic attack by the chiral Cu-azomethine ylide, the formation of which is simultaneously facilitated by Et3 B, affording α-quaternary α-amino acids with high regioselectivity and excellent stereoselectivity. The use of readily available allylic alcohols as electrophilic precursors represents an improvement from an environmental and atom/step economy perspective. Computational mechanistic studies reveal the crucial role of the Et3 B additive and the origins of stereo- and regioselectivities by analyzing steric effects, dispersion interactions, and frontier orbital population.

Palladium-Catalyzed Regiodivergent Synthesis of 1,3-Dienyl and Allyl Esters from Propargyl Esters.

Catalyst-controlled regiodivergent catalysis is a vital chemical tool that allows efficient access to large collections of structurally diverse molecules from a common precursor but remains a challenge. We report a catalyst-controlled, tunable, and predictable regiodivergency in transforming the internal aliphatic propargyl esters into diverse libraries of highly substituted 1,3-dienyl and allyl products by Pd-catalysis. Depending on the ligand employed, the palladium catalyst can involve two typical approaches: electrophilic palladium catalysis and a sequential oxidative addition-reductive elimination pathway. This regiodivergent protocol endows facile access to four regioisomers with high regio- and stereoselectivity from the common propargyl esters. In terms of synthetic utility, a notable feature of this protocol is amenable to structural diversification of bioactive relevant molecules, enabling rapid assembly of many useful structural analogs of pharmaceutical candidates.

Enantioselective Allylation of Alkenyl Boronates Promotes a 1,2-Metalate Rearrangement with 1,3-Diastereocontrol.

Alkenyl boronates add to Ir(π-allyl) intermediates with high enantioselectivity. A 1,2-metalate shift forms a second C-C bond and sets a 1,3-stereochemical relationship. The three-component coupling provides tertiary boronic esters that can undergo multiple additional functionalizations. An extension to trisubstituted olefins sets three contiguous stereocenters.

Total Synthesis of Leiodermatolide A via Transfer Hydrogenative Allylation, Crotylation, and Propargylation: Polyketide Construction beyond Discrete Allyl- or Allenylmetal Reagents.

The total synthesis of leiodermatolide A was accomplished in 13 steps (LLS). Transfer hydrogenative variants of three carbonyl additions that traditionally rely on premetalated reagents (allylation, crotylation, and propargylation) are deployed together in one total synthesis.

Overhauser Dynamic Nuclear Polarization with Selectively Deuterated BDPA Radicals.

The Overhauser effect (OE), commonly observed in NMR spectra of liquids and conducting solids, was recently discovered in insulating solids doped with the radical 1,3-bisdiphenylene-2-phenylallyl (BDPA). However, the mechanism of polarization transfer in OE-DNP in insulators is yet to be established, but hyperfine coupling of the radical to protons in BDPA has been proposed. In this paper we present a study that addresses the role of hyperfine couplings via the EPR and DNP measurements on some selectively deuterated BDPA radicals synthesized for this purpose. Newly developed synthetic routes enable selective deuteration at orthogonal positions or perdeuteration of the fluorene moieties with 2H incorporation of >93%. The fluorene moieties were subsequently used to synthesize two octadeuterated BDPA radicals, 1,3-[α,γ-d8]-BDPA and 1,3-[ß,δ-d8]-BDPA, and a BDPA radical with perdeuterated fluorene moieties, 1,3-[α,ß,γ,δ-d16]-BDPA. In contrast to the strong positive OE enhancement observed in degassed samples of fully protonated h21-BDPA (ε ∼ +70), perdeuteration of the fluorenes results in a negative enhancement (ε ∼ -13), while selective deuteration of α- and γ-positions (aiso ∼ 5.4 MHz) in BDPA results in a weak negative OE enhancement (ε ∼ -1). Furthermore, deuteration of ß- and δ-positions (aiso ∼ 1.2 MHz) results in a positive OE enhancement (ε ∼ +36), albeit with a reduced magnitude relative to that observed in fully protonated BDPA. Our results clearly show the role of the hyperfine coupled α and γ 1H spins in the BDPA radical in determining the dominance of the zero and double-quantum cross-relaxation pathways and the polarization-transfer mechanism to the bulk matrix.

Enantioselective Hydrothiolation: Diverging Cyclopropenes through Ligand Control.

In this article, we advance Rh-catalyzed hydrothiolation through the divergent reactivity of cyclopropenes. Cyclopropenes undergo hydrothiolation to provide cyclopropyl sulfides or allylic sulfides. The choice of bisphosphine ligand dictates whether the pathway involves ring-retention or ring-opening. Mechanistic studies reveal the origin for this switchable selectivity. Our results suggest the two pathways share a common cyclopropyl-Rh(III) intermediate. Electron-rich Josiphos ligands promote direct reductive elimination from this intermediate to afford cyclopropyl sulfides in high enantio- and diastereoselectivities. Alternatively, atropisomeric ligands (such as DTBM-BINAP) enable ring-opening from the cyclopropyl-Rh(III) intermediate to generate allylic sulfides with high enantio- and regiocontrol.

Enantioselective Ruthenium-BINAP-Catalyzed Carbonyl Reductive Coupling of Alkoxyallenes: Convergent Construction of syn-sec,tert-Diols via (Z)-σ-Allylmetal Intermediates.

The first catalytic enantioselective ruthenium-catalyzed carbonyl reductive couplings of allene pronucleophiles is described. Using an iodide-modified ruthenium-BINAP-catalyst and O-benzhydryl alkoxyallene 1a, carbonyl (α-alkoxy)allylation occurs from the alcohol or aldehyde oxidation level to form enantiomerically enriched syn-sec,tert-diols. Internal chelation directs intervention of (Z)-σ-alkoxyallylruthenium isomers, which engage in stereospecific carbonyl addition.

Novel enzymatic single-nucleotide modification of DNA oligomer: prevention of incessant incorporation of nucleotidyl transferase by ribonucleotide-borate complex.

Terminal deoxynucleotidyl transferase (TdT), which mediates template-independent polymerization with low specificity for nucleotides, has been used for nucleotide extension of DNA oligomers. One concern is that it is difficult to control the number of incorporated nucleotides, which is a limitation on the use of TdT for single-nucleotide incorporation of DNA oligomers. Herein, we uncovered an interesting inhibitory effect on TdT when ribonucleotide substrates (rNTPs) were employed in a borate buffer. On the basis of unique inhibitory effects of the ribonucleotide-borate complex, we developed a novel enzymatic method for single-nucleotide incorporation of a DNA oligomer with a modified rNTP by TdT. Single-nucleotide incorporation of a DNA oligomer with various modified rNTPs containing an oxanine, biotin, aminoallyl or N6-propargyl group was achieved with a high yield. The 'TdT in rNTP-borate' method is quite simple and efficient for preparing a single-nucleotide modified DNA oligomer, which is useful for the design of functional DNA-based systems.