Glycosylation of 2-(2-Propylsulfinyl)benzyl 1,2-Orthoester Glycosides Initiated by Sulfoxide Activation.

We have developed a highly effective glycosylation method that involves the activation of 2-(2-propylsulfinyl)benzyl 1,2-orthoester glycosides using triflic anhydride (Tf2O). Our research indicates that half of the glycosyl donor is activated through Tf2O via an interrupted Pummerer reaction mechanism, while the remaining portion is activated by triflic acid (TfOH) generated in situ. As a result, as little as 0.5 equiv of Tf2O is adequate for activating the orthoester glycoside donors. This glycosylation procedure offers several benefits, such as high efficiency, wide applicability, and the utilization of a recyclable leaving group.

An efficient metal-free desulfurization strategy promoted by Togni-II reagent.

Desulfurization is a versatile synthetic tool in organic synthesis, particularly in peptide chemistry, where it offers an effective conversion strategy for compounds that contain mercaptan groups. In this study, we present a metal-free desulfurization method for amino acids and peptides using a Togni-II reagent as a radical initiator. Our method showed excellent efficiency and extensive substrate tolerance, circumventing the formation of radical adducts caused by VA-044. The obtained results further expand the applicability of Togni-II reagent as a key promotor in radical-based reactions.

Exogenous Phytosulfokine α (PSKα) Alleviates Chilling Injury of Kiwifruit by Regulating Ca2+ and Protein Kinase-Mediated Reactive Oxygen Species Metabolism.

Kiwifruit fruit stored at low temperatures are susceptible to chilling injury, leading to rapid softening, which therefore affects storage and marketing. The effect of 150 nM mL-1 of exogenous phytosulfokine α (PSKα) on reactive oxygen species (ROS) metabolism, Ca2+ signaling, and signal-transducing MAPK in kiwifruit, stored at 0 °C for 60 days, was investigated. The results demonstrated that PSKα treatment effectively alleviated chilling injury in kiwifruit, with a 15% reduction in damage compared to the control on day 60. In addition, PSKα enhanced the activities and gene expression levels of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR), Ca2+-ATPase, and mitogen-activated protein kinase (MAPK). In contrast, the activities and gene expression levels of NADPH oxidase (NOX) were inhibited, leading to a lower accumulation of O2- and H2O2, which were 47.2% and 42.2% lower than those in the control at the end of storage, respectively. Furthermore, PSKα treatment enhanced the calmodulin (CaM) content of kiwifruit, which was 1.41 times that of the control on day 50. These results indicate that PSKα can mitigate chilling injury and softening of kiwifruit by inhibiting the accumulation of ROS, increasing antioxidant capacity by inducing antioxidant enzymes, activating Ca2+ signaling, and responding to MAPK protein kinase. The present results provide evidence that exogenous PSKα may be taken for a hopeful treatment in alleviating chilling injury and maintaining the quality of kiwifruit.

Recyclable fluorous-tag assisted two-directional oligosaccharide synthesis enabled by interrupted Pummerer reaction mediated glycosylation.

Herein, we report a novel fluorous-tag assisted two-directional oligosaccharide assembly strategy, which maintained the high coupling efficiency of solution-phase synthesis and featured the advantage of an easy purification process comparable to solid-phase synthesis. A well-designed fluorous tag was decorated on the latent anomeric leaving group in interrupted Pummerer reaction mediated (IPRm) glycosylation. The high efficiency of the in-solution phase glycosylation and the unique affinity of the fluorous tag towards polytetrafluoroethylene (PTFE) particles allowed flexible assembly from the reducing end to the non-reducing end and fast purification by PTFE-assisted filtration. Moreover, the fluorous-tagged latent anomeric leaving group could be activated by oxidation and cleaved by IPRm glycosylation, thus enabling the elongation of the carbohydrate chain from the non-reducing end to the reducing end as well as the recovery of the fluorous tag. The present two-directional synthetic strategy is used to assemble the repeating unit of Streptococcus pneumoniae type 14 capsular polysaccharide.

Rhenium(V)-catalyzed synthesis of 1,1'-2-deoxy thioglycosides.

As stable glycomimetics, thioglycosides are important tools for the investigation of biological processes and discovery of new drugs. In this note, we report a ReOCl3(SMe2)(OPPh3) catalyzed coupling reaction between ß-glycosyl thiols (1-thio sugars) and glycals for the preparation of 1,1'-α,ß-2-deoxy thioglycosides, which are glycomimetics of natural trehalose and 2-deoxy glycosides. Furthermore, an S-linked trisaccharide was successfully obtained by successive employment of the Re(V) catalyzed thioglycosylation protocol.

Structurally diverse diterpenoids from Pieris japonica as potent analgesics.

Sixteen diterpenoids (1-16) including 10 new ones, pierisjaponins A-J (1-10), were isolated and identified from Pieris japonica, and their structures were classified into eight diverse carbon skeletons. Pierisjaponins A (1) and B (2) represent the first 1,5-seco-grayanane diterpenoid glucosides and only showed 17 carbon resonances instead of 26 carbons in the 13C NMR spectra, their structures were finally defined by single-crystal X-ray diffraction, and the unusual NMR phenomena were explained. Pierisjaponin E (5) is the first mollane diterpene glucoside. This is the first time to report ent-labdane (3, 4, and 11) and ent-rosane (15) type diterpenoids from the Ericaceae plants, which provided the precursors of the Ericaceae diterpenoids and enlarged the chemical diversity of Ericaceae diterpenoids. All the 16 isolates showed potent analgesic activities, and this is the first time to describe the analgesic activities of 1,5-seco-grayanane, ent-labdane, mollane, and ent-rosane type diterpenoids. A preliminary structure-activity relationship is discussed, which provided new clues to design novel analgesics based on the Ericaceae diterpenoids.

Application of Interrupted Pummerer Reaction Mediated (IPRm) Glycosylation in Natural Product Synthesis.

Although numerous glycosylation methods have been developed for the construction of glycosidic bonds, the pace of discovering rapid assembly strategies to access complex glycosidic linkages never stops. Over the last several years, we have introduced interrupted Pummerer reaction into carbohydrate chemistry and developed two pairs of latent/active glycosyl donors, OPTB/OPSB and SPTB/SPSB glycosides. After thorough investigation of the reaction mechanism and establishment of the substrate scopes, the extension of these novel glycosylation methods to synthesize naturally occurring biological active glycoconjugates was further illustrated. In this account, the development and especially the application of IPRm glycosylation in the synthesis of phenylethanoids and resin glycosides were introduced.

Water Compatible Hypophosphites-d2 Reagents: Deuteration Reaction via Deutero-deiodination in Aqueous Solution.

Contrary to conventional deuteration approaches which typically entail deuterated solvents and/or moisture exclusion, an unprecedented deutero-deiodination reaction attainable in aqueous (H2O) solution is presented herein. By utilizing the stability of inorganic deuterated calcium/sodium hypophosphites against wayward H/D isotopic exchange within pH 2.5-11.7, these shelf-stable, nontoxic, cost-effective, and environmentally benign deuteration reagents mediate deuteration of a broad range alkyl and aryl iodides with ample isotopic incorporation in aqueous (H2O) solution.

Grayanane diterpenoid glucosides as potent analgesics from Pieris japonica.

A total of fifteen grayanane diterpenoid glucosides including eight undescribed ones, pierisjaponosides A-H, were isolated from the leaves of Pieris japonica (Thunb.) D. Don ex G. Don (Ericaceae). Their structures were established by extensive spectros copic techniques including HRESIMS and NMR, as well as chemical methods. The absolute configurations of pierisjaponosides A, B, and D were finally established by single-crystal X-ray diffraction with Cu Kα radiation. This is the first time to report the crystal structure of a 5,9-epoxygrayanane diterpenoid glucoside. Pierisjaponoside E represents the first example of a 9ß-hydroxygrayan-1(10)-ene diterpenoid. All the isolated grayanane diterpenoid glucosides were evaluated for their analgesic activities in the acetic acid-induced writhing models in mice, and showed significant analgesic effects. Pierisjaponosides A and C-H, micranthanoside A, pieroside A, and craiobiosides A and B displayed significant analgesic effects with the writhe inhibition rates over 50% at a dose of 5.0 mg/kg. Pierisjaponoside E exhibited significant analgesic activities with the percentage inhibitions of 81.7%, 70.4%, and 52.1% at the doses of 5.0, 1.0, and 0.2 mg/kg, respectively. The preliminary structure-activity relationships of grayanane diterpenoid glucosides as potent analgesics were discussed, giving some clues to design novel analgesics.

Antinociceptive Grayanane Diterpenoids from the Leaves of Pieris japonica.

Thirteen new grayanane diterpenoids (1-13) and 15 known analogues (14-28) were isolated from a leaf extract of Pieris japonica. Their structures were determined by spectrometric and spectroscopic methods, including HRESIMS, NMR, IR, and UV. The absolute configurations of 1, 3, 7-9, and 16 were defined by single-crystal X-ray diffraction analysis. 17-Hydroxygrayanotoxin XIX (1) represents the first example of a 17-hydroxygrayan-15(16)-ene diterpenoid. Diterpenoids 1-28 were evaluated for their antinociceptive activities, and 4, 9, 13, 21, and 26-28 displayed significant antinociceptive activities at a dose of 5.0 mg/kg (ip) in the HOAc-induced writhing test in mice. 17-Hydroxygrayanotoxin XIX (1) exhibited potent antinociceptive effects with writhe inhibition rates of 56.3% and 64.8% at doses of 0.04 and 0.2 mg/kg, respectively, which were almost equivalent to the positive control, morphine. Rhodomollein X (26) and rhodojaponin VI (27) showed more potent antinociceptive effects than morphine at doses of 0.04 and 0.2 mg/kg. A preliminary structure-activity relationship for the antinociceptive effects of diterpenoids 1-28 is discussed.

Glycosylation Enabled by Successive Rhodium(II) and Brønsted Acid Catalysis.

Herein, we reported on a highly efficient glycosylation reaction comprising two chronological meticulously designed catalytic cycles: (1) rhodium-catalyzed formation of sulfonium ylide and (2) Brønsted acid-catalyzed formation of sulfonium ion. This protocol highlighted an effective and robust tactic to prepare a glycosyl sulfonium ion from a glycosyl sulfonium ylide precursor amenable for glycosylation.

Total Syntheses of Resin Glycosides Murucoidins IV and V.

Murucoidins IV and V, two bioactive resin glycosides with complex yet similar structures isolated from the morning glory family, were synthesized in a convergent manner. All of the glycosylations in these syntheses including the key [3 + 2] coupling were achieved by our recently developed interrupted Pummerer reaction mediated (IPRm) glycosylations. The broad functional group compatibility of IPRm glycosylation allowed us to employ a latent-active concept and a single-pot transient protection-glycosylation-deprotection strategy which significantly improved the global synthetic efficiency.

Groundwater level changes with a focus on agricultural areas in the Mid-Atlantic region of the United States, 2002-2016.

Climate change impacts all water sources, including high quality groundwater that supplies agricultural irrigation in many regions of the United States. This study assessed groundwater level changes in the U.S. Mid-Atlantic region with a focus on cultivated areas. Trends of groundwater level were estimated using linear regression, and examined for shallow, medium, and deep depths across physiographic regions of Mid-Atlantic. A hotspot analysis was conducted to identify spatial clusters of wells with rising or declining groundwater levels. In addition, differences in the percentage of cultivated area with declining groundwater between cultivated land categories was examined at the county level. From 2002-2016, the Mid-Atlantic region had an overall decline in groundwater level (0.06 m/yr, 95% CI: 0.03, 0.09) although groundwater changes varied by physiographic regions. The Coastal Plain physiographic region was dominated by declining groundwater wells (48%) and had the most significant groundwater level declines (0.23 m/yr, 95% CI: 0.19, 0.26). Significant groundwater level rises were detected in Southern Virginia adjacent to the Chesapeake Bay (0.92 m/yr on average), which could be due to the cessation of groundwater withdrawal from one of the region's largest groundwater users. In the Mid-Atlantic region, shallow groundwater was found to have slight rising trends (0.08 m, p < 0.05) while deeper groundwater showed distinctive declining trends (1.36 m, p < 0.05) between 2002 and 2016. There were significantly more cultivated areas with declining groundwater levels (88% vs. 35%, p < 0.05) in counties with high percentages of cropland (> 50%) compared to areas covered by less cropland. As climate and human pressures increase, it will be critical to identify and evaluate alternative water sources, such as reclaimed water, to sustain agricultural production and protect groundwater resources.

SWCTI: Surface Water Content Temperature Index for Assessment of Surface Soil Moisture Status.

The vegetation supply water index (VSWI = NDVI/LST) is an effective metric estimating soil moisture in areas with moderate to dense vegetation cover. However, the normalized difference vegetation index (NDVI) exhibits a long water stress lag and the land surface temperature (LST), sensitive to water stress, does not contribute considerably to surface soil moisture monitoring due to the constraints of the mathematical characteristics of VSWI: LST influences VSWI less when LST value is sufficiently high. This paper mathematically analyzes the characteristics of VSWI and proposes a new operational dryness index (surface water content temperature index, SWCTI) for the assessment of surface soil moisture status. SWCTI uses the surface water content index (SWCI), which provides a more accurate estimation of surface soil moisture than that of NDVI, as the numerator and the modified surface temperature, which has a greater influence on SWCTI than that of LST, as the denominator. The validation work includes comparison of SWCTI with in situ soil moisture and other remote sensing indices. The results show SWCTI demonstrates the highest correlation with in situ soil moisture; the highest correlation R = 0.801 is found between SWCTI and the 0⁻5 cm soil moisture in a sandy loam. SWCTI is a functional and effective method that has a great potential in surface soil moisture monitoring.

Glycosyl Sulfoxides in Glycosylation Reactions.

Carbohydrate chemistry has benefited a lot from the intrinsic reactivity of sulfoxide since it was introduced in glycosylation reactions by Kahne in 1989. Since then, extensive studies have been explored by employing sulfoxide as glycosyl donors and activation reagents in construction of glycosidic bonds. As glycosyl donors, the sulfinyl groups could locate either directly or remotely at anomeric position. This chapter focuses on the establishment and development of sulfoxides as glycosyl donors in glycosylation reactions, with an emphasis on their applications and postulated mechanisms.

Tracking the leaving group in the remote activation of O-2-[(propan-2-yl)sulfinyl]benzyl (OPSB) glycoside.

In our recently developed interrupted Pummerer reaction mediated glycosylation with O-2-[(propan-2-yl)sulfinyl]benzyl (OPSB) glycosides as glycosyl donors, the anomeric leaving group was recovered as a benzyl alcohol which didn't affect the glycosylation efficiency. To investigate the mechanism of the occurrence of this alcohol, an 18O isotopic labeling reaction was carried out to track the leaving group. It was found that the benzyl alcohol was generated during the aqueous work up process from an inactive cyclic oxo-sulfonium ion intermediate. It was also proved that H2O prefer to attack the sulfur atom position during the hydrolysis of the intermediate.

Palladium-catalyzed aerobic (1+2) annulation of Csp3-H bonds with olefin for the synthesis of 3-azabicyclo[3.1.0]hex-2-ene.

A novel palladium-catalyzed aerobic (1+2) annulation was developed for the synthesis of 3-azabicyclo[3.1.0]hex-2-ene. The palladation of Csp3-H bonds took place twice at the same position in the whole reaction process. Preliminary mechanistic studies by in situ IR revealed that the second C-H palladation and reductive elimination might be slow steps.

Thiophene-Fused π-Systems from Diarylacetylenes and Elemental Sulfur.

A simple yet effective method for the formation of thiophene-fused π-systems is reported. When arylethynyl-substituted polycyclic arenes were heated in DMF in the presence of elemental sulfur, the corresponding thiophene-fused polycyclic arenes were obtained via cleavage of the ortho-C-H bond. Thus, arylethynylated naphthalenes, fluoranthenes, pyrenes, corannulenes, chrysenes, and benzo[c]naphtho[2,1-p]chrysenes were effectively converted into the corresponding thiophene-fused π-systems. Apart from polycyclic hydrocarbons, thiophene derivatives are also susceptible to this reaction. The practical utility of this reaction is demonstrated by preparations on the decagram scale, one-pot two-step reaction sequences, and multiple thiophene annulations.

Copper-catalyzed aerobic oxidative coupling: From ketone and diamine to pyrazine.

Copper-catalyzed aerobic oxidative C-H/N-H coupling between simple ketones and diamines was developed toward the synthesis of a variety of pyrazines. Various substituted ketones were compatible for this transformation. Preliminary mechanistic investigations indicated that radical species were involved. X-ray absorption fine structure experiments elucidated that the Cu(II) species 5 coordinated by two N atoms at a distance of 2.04 Å and two O atoms at a shorter distance of 1.98 Å was a reactive one for this aerobic oxidative coupling reaction. Density functional theory calculations suggested that the intramolecular coupling of cationic radicals was favorable in this transformation.

Palladium catalysed ß-selective oxidative Heck reaction of an electron-rich olefin.

A palladium catalysed oxidative ß-arylation of an electron-rich olefin is described. The reaction was under mild conditions; meanwhile, additives and directing groups are not needed. Various arylboronic acids worked well under the standard conditions.