Sequential 1,4-/1,2-Addition of Lithium(trimethylsilyl)diazomethane onto Cyclic Enones to Induce C-C Fragmentation and N-Li Insertion.

α,ß-Unsaturated ketones generally undergo addition reactions with nucleophiles with a preference for either 1,2- or 1,4-addition, but rarely both. However, the right combination of reagents allows for consecutive 1,4- and 1,2-additions to occur: Cyclic α,ß-unsaturated ketones undergo double additions with lithium(trimethylsilyl)diazomethane, effectively generating various molecular frameworks with complexity and diversity. Owing to the sequential generation of several intermediates of multifaceted reactivity, including diazoalkane derivatives and alkylidene carbenes, it is possible to induce novel Grob-type C-C fragmentations, alkylidene carbene mediated Li-N insertions, and dipolar cycloadditions by controlling the reaction parameters.

Synthesis of Amathaspiramides by Aminocyanation of Enoates.

Concise routes for the total and formal syntheses of the amathaspiramides were developed through a formal [3+2] cycloaddition between lithium(trimethylsilyl)diazomethane and α,ß-unsaturated esters. The effectiveness of this new cycloaddition for the construction of Δ(2)-pyrazolines containing a α-tert-alkylamino carbon center and subsequent facile protonolytic N-N bond cleavage allows the synthesis of a key intermediate of the amathaspiramides and other α,α-disubstituted amino acid derivatives.

A catalytic enantiotopic-group-selective Suzuki reaction for the construction of chiral organoboronates.

Catalytic enantiotopic-group-selective cross-couplings of achiral geminal bis(pinacolboronates) provide a route for the construction of nonracemic chiral organoboronates. In the presence of a chiral monodentate taddol-derived phosphoramidite ligand, these reactions occur with high levels of asymmetric induction. Mechanistic experiments with chiral (10)B-enriched geminal bis(boronates) suggest that the reaction occurs by a stereochemistry-determining transmetalation that occurs with inversion of configuration at carbon.

Formal aminocyanation of α,ß-unsaturated cyclic enones for the efficient synthesis of α-amino ketones.

Installation of amino functionality on organic molecules through direct CN bond formation is an important research objective. To achieve this goal, a 1,2-aminocyanation reaction was developed. The reaction occurs through the formation of pyrazolines by means of a formal dipolar cycloaddition of cyclic α,ß-unsaturated ketones with lithium trimethylsilyldiazomethane followed by novel protonolytic N-N bond cleavage under mild conditions. This two-step process provides a diverse array of structurally complex free and mono-alkylated α-amino ketones in excellent yields.

Retrogradation inhibition of starches in staple foods with maltotetraose-forming amylase.

To effectively inhibit the retrogradation of staple foods, the effects of maltotetraose-forming amylase(G4-amylase) on the short and long-term retrogradation of different staple starches such as rice starch (RS), wheat starch (WS), potato starch (PS) were studied. The results indicated that G4-amylase decreased the content of amylose. Amylose contents (21.09%) of WSG4 were higher than that (14.82%) of RSG4 and (13.13%) of PSG4. WS had the most obvious change in the chain length distribution of amylopectin. A chains decreased by 18.99% and the B1 chains decreased by 12.08% after G4-amylase treatment. Compared to RS (662 cP) and WS (693 cP), the setback viscosity of RSG4 (338 cP) and WSG4 (385 cP) decreased. Compared to RS (0.41), WS (0.45), and PS (0.51), the long-term retrogradation rate of RSG4 (0.33), WSG4 (0.31), and PSG4 (0.38) significantly reduced. It indicated that G4-amylase significantly inhibited the long-term retrogradation of WS, followed by RS and PS.

Enantio- and Diastereoselective Total Synthesis of Belzutifan Enabled by Rh-Catalyzed Hydrogenation.

Herein, we report a nine-step synthesis of belzutifan enabled by a novel Rh-catalyzed asymmetric hydrogenation to install the contiguous fluorinated stereocenters with high enantioselectivity. Moreover, the final ketone reduction in the synthesis proceeds with high diastereoselectivity, leading to the expedient assembly of the stereotriad. In contrast to the original 16-step synthesis, this route avoids a lengthy bromination-oxidation sequence and introduces the sulfone functionality via nucleophilic aromatic substitution, obviating the need for transition metal catalysis.

Theoretical studies on the mechanism of the C-H amination of silyl cyclopropenes by azodicarboxylates.

DFT/M06 calculations were carried out to better understand the mechanism and regio- and chemoselectivities of our previously discovered formal C-H amination of silyl cyclopropenes by azodicarboxylates (Chem. Commun. 2012, 48, 10990). The results revealed that the initial Alder-ene reaction between the two reactants follows a stepwise mechanism and the subsequent allylic transposition proceeds via a concerted [1,3]-migration of hydrazodicarboxylate. For the Alder-ene process of 1-silyl-2-methylcyclopropene, different electronic effects of the substituents make the C1 much more negatively charged and thus more reactive than C2 in the regiochemistry-determining electrophilic azodicarboxylate addition step. In addition, the poor regioselectivity caused by a C2 ether linkage and the lower reactivity of ene donors other than cyclopropenes with azodicarboxylate were well explained by the computational results. Furthermore, the divergent allylic transposition of the Alder-ene intermediates was rationalized, and the steric repulsion between the silyl group and the hydrazodicarboxylate moiety was suggested as the driving force in promoting the allylic transposition. The barrier for the rate-controlling [1,3]-migration of hydrazodicarboxylate from an intermediate containing the C1-N bond is 21.1 kcal/mol, whereas a higher barrier of 27.5 kcal/mol is required for the similar rearrangement of the thermodynamically more stable intermediate containing the C2-N bond.

New methylene homologation method for cyclic ketones.

Teaching new tricks to an old dog: By intercepting adducts between ketones and lithium trimethylsilyldiazomethane, a new Tiffeneau-Demjanov type methylene homologation could be realized in a single-step operation. Among proton sources and Lewis acids, silica gel was found to be the most effective reagent for the protonation of intermediates and their subsequent ring expansion (see scheme).

Resistant structure of extruded starch: Effects of fatty acids with different chain lengths and degree of unsaturation.

This study investigated the formation mechanism of enzyme-resistant structures in extruded starch, specifically, fatty acid-starch complexes (FASCs). The effects of fatty acids (FAs) with different carbon-chain lengths (C12-C18) and degrees of unsaturation (C18:0-C18:2) on complex formation were evaluated, with fluorescence microscopy verifying complex formation. The complexed-lipid content and degree of relative crystallinity increased with the carbon-chain length and degree of FA unsaturation. FAs with fewer carbons were more likely to generate stable complexes (e.g., form II, melted at 100-120 °C), while FAs with more carbons tended to produce relatively unstable complexes (e.g., form I, melted at 80-100 °C). After reheating and cooling, a new amylose-lipid complex and an amylose-amylopectin network was formed in the unsaturated FASC samples, which restricted the penetration of enzymes into starch granules. A starch-linoleic acid complex exhibited the highest resistant starch content (15.7%) and lowest predicted glycaemic index (88.4).

Metal-catalyzed rearrangement of cyclopropenes to allenes.

A novel transition-metal-catalyzed rearrangement of silylated cyclopropenes to the corresponding allenes is described. The presence of both the trimethylsilyl group on the cyclopropene and the platinum catalyst are crucial for this rearrangement.

Selectivity control in alkylidene carbene-mediated C-H insertion and allene formation.

Regioselectivity of alkylidene carbene-mediated C-H insertion was explored utilizing electronic, conformational, steric, and stereoelectronic effects. Relying on these factors, highly regio- and chemoselective carbene insertion reaction of C-H bonds in different environments could be obtained. The observed selectivity clearly indicates that an electronic effect plays a more important role than steric effect. In general, C-H bonds in conformationally rigid cyclic environments are less reactive than those in acyclic systems toward carbene insertion, and in this situation, a competing intermolecular reaction between alkylidene carbene and trimethylsilyldiazomethane led to the formation of allenylsilanes. The formation of allenylsilane becomes more favorable as the concentration of reaction becomes higher, as well as the C-H bonds undergoing insertion becomes electronically and conformationally deactivated.

Mechanism of effect of endogenous/exogenous rice protein and its hydrolysates on rice starch digestibility.

The role of endogenous/exogenous rice protein and its hydrolysates in the enzymatic hydrolysis resistance of rice starch was investigated. Scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM) and Fourier transform infrared spectroscopy (FTIR) results showed that different types of rice endogenous proteins retarded the digestion of rice starch by the same way. Exogenous addition of protein hydrolysates was more effective than protein for impeding starch digestion. FTIR results indicated that rice protein hydrolysates were bound to starch granules through hydrogen bonds, and their interaction strengthened the ordered structure of the starch. Further, the intensity of the starch V- type peak was enhanced after the addition of protein hydrolysates, indicating that some peptides or free amino acids released by the protein formed complexes with the starch, thereby contributing to high slowly-digestible starch content. These findings provide a theoretical basis for the preparation of low glycemic index starch-based foods.

Characterization the structural property and degradation behavior of corn starch in KOH/thiourea aqueous solution.

Finding an efficient and eco-friendly solution for starch dissolution has attracted considerable attentions in recent years. This study investigated the structural characteristics, and degradation behavior of corn starch in KOH/thiourea aqueous solution by the comparison with DMSO/LiBr and 1-allyl-3-methylimidazolium chloride (AMIMCl). Results showed that KOH/thiourea solution was an effective solvent for corn starch dissolution (30 min with 97.01% solubility). X-ray diffraction (XRD) and 13C CP-MAS NMR spectroscopy revealed that native crystallinity of the corn starch was altered by all tested solvents, especially DMSO/LiBr and AMIMCl. Conversely, this new solvent did not change the primary molecular structure, chain-length distribution, or thermal stability of starch, compared with the native starch. Furthermore, KOH/thiourea solution was more suitable for measuring the molecular weight of corn starch, with a weight-average molecular weight (Mw) of 7.18 × 107 g/mol. Therefore, KOH/thiourea solution is a promising novel solvent for starch dissolution and structural exploration.

Type III Resistant Starch Prepared from Debranched Starch: Structural Changes under Simulated Saliva, Gastric, and Intestinal Conditions and the Impact on Short-Chain Fatty Acid Production.

Type III resistant starch (RS3) has high resistance to enzymatic digestibility and benefits colonic bacteria by producing short-chain fatty acids (SCFAs) via fermentation. Studies have delineated RS preparation and the description of RS fractions with different types of starch, but the digestion process has received little attention. The molecular and crystalline structure changes, thermal properties, and SCFA content of RS3 obtained from debranched starch were investigated in simulated salivary, gastric, and intestinal digestion systems. The average degree of polymerization and the melting enthalpy change of the digested RS3 residues increased; a high molecular order was reflected by the higher relative crystallinity. Fine structural changes suggested that enzyme-resistant starch might form during digestion by the rearrangement of short amylose chains into enzyme-resistant structures with higher relative crystallinity. After fermentation of human feces, RS3 increased the SCFA content, especially of butyric acid, indicating that this recrystallized RS3 could be a new prebiotic product.

Cyclopropenation of alkylidene carbenes derived from alpha-silyl ketones.

A new cyclopropanation reaction involving Calpha-Si bond insertion of alkylidene carbenes derived from alpha-silyl ketones has been developed. This unprecedented alkylidene carbene reactivity features excellent selectivity for insertion into Calpha-Si bonds rather than insertion into Cgamma-H bonds or addition to gamma,delta-double or -triple bonds. The selectivity trend clearly indicates that the alpha-oxygen in the tether significantly promotes Cgamma-H insertion, although the Calpha-Si bond insertion still competes effectively.

Preparation and characterization of zwitterionic functionalized starch nanoparticles.

Zwitterionic polymers have attracted great attention due to their unique structure, which can be used for various applications, such as the improvement of nanoparticle stability, ion exchange, sewage treatment, and biomedicine. Here, zwitterionic functionalized starch nanoparticles (SNPs) were successfully prepared in two steps by carboxymethylation and quaternization. The structure of the modified SNPs was confirmed using Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and elemental analysis. The zwitterionic SNPs with a size of 30-100 nm were well dispersed without aggregation. The relative crystallinity of zwitterionic SNPs (35.2%) was increased compared to that of SNPs (31.7%). The zwitterionic SNPs could be used effectively to absorb dyes, and its isoelectric point was around pH 9.4. The zwitterionic SNPs may be used as nontoxic adsorption carriers that can be used in health foods or drug delivery applications.

Effects of pullulanase debranching on the properties of potato starch-lauric acid complex and potato starch-based film.

The effects of different debranching time on the properties of potato starch and its films were evaluated. Potato starch granules were debranched with pullulanase for 0, 0.5, 1.0, 1.5 or 2.0 h. The effects of pullulanase debranching treatment on the chain-length distributions of amylopectin were analysed by high performance anion exchange chromatography (HPAEC), which proved that the shorter debranching treatment generated more linear chains with favourable lengths to facilitate the formation of potato starch-lauric acid complexes. The debranched starch-lipid complexes showed higher lauric acid content than that of the untreated sample. X-ray diffraction showed that the diffraction intensity of the debranched sample was stronger than that of the undebranched sample, and when the debranching time was >1.5 h, the diffraction intensity and relative crystallinity of the complexes decreased. The sample exhibited a high melting enthalpy (ΔH) under the pullulanase debranching treatment for 1.5 h. Scanning electron microscope data indicated that the surface of the composite film was flatter after the debranching treatment and that the films exhibited the lowest water vapour permeability and highest tensile strength after the treatment time for 1.5 h.

Interactions between debranched starch and emulsifiers, polyphenols, and fatty acids.

Debranching modifications of waxy corn starch with pullulanase can generate short-chain amylose or debranched starch (DBS), which is easy to recrystallize. Herein, we firstly investigated the regulation of recrystallization behaviors of DBS by studying the interactions between DBS and emulsifiers, polyphenols, and fatty acids. Sodium dodecyl sulfate at the 3.0% level had strong interactions with DBS. When the concentration of epigallocatechin gallate was 15%, the enthalpy change (ΔH) of DBS was close to 0 J/g and the relative crystallinity of DBS was 0, clearly indicating the strong interactions between epigallocatechin gallate and DBS. When the concentration of caproic acid, caprylic acid, and capric acid increased from 0 to 20.0%, the ΔH of DBS decreased from 11.38 ± 0.01 to 3.90 ± 0.63, 1.39 ± 0.21, and 3.98 ± 0.83 J/g, respectively. The interactions between emulsifiers, polyphenols, and fatty acids and DBS could affect physiochemical properties of DBS in varying degrees.

Characterization of Cationic Modified Debranched Starch and Formation of Complex Nanoparticles with κ-Carrageenan and Low Methoxyl Pectin.

The functional modifications of debranched starch (DBS) has been attracting the interest of researchers. This study marks the first time that DBS was modified by cationization through the use of (3-chloro-2-hydroxypropyl) trimethylammonium chloride with the introduction of cationic functional groups. The physicochemical properties and structural characteristics of cationized debranched starch (CDBS) were systematically assessed. The results demonstrate that the maximum degree of substitution (DS) value obtained was as high as 1.14, and the corresponding CDBS exhibited significantly higher zeta potential values: approximately +35 mV. The minimal inhibitory concentration values of the CDBS of DS 1.14 against Escherichia coli and Staphylococcus aureus were 6 and 8 mg mL-1, respectively. In addition, nanoparticles were successfully prepared with a combination of CDBS and low methoxyl pectin (LMP) and a combination of CDBS and κ-carrageenan (CRG). The maximum encapsulation efficiency of nanoparticles for (-)-epigallocatechingallate can reach 87.8%.

Green preparation and characterization of starch nanoparticles using a vacuum cold plasma process combined with ultrasonication treatment.

In this study, starch nanoparticles (SNPs) were fabricated via a facile and green method involving a vacuum low-temperature plasma process combined with rapid ultrasonication treatment using waxy corn starch (WCS) and potato starch (PS). Morphology, size, crystalline structure, thermal property, and stability analyses of the SNPs were systematically performed. The obtained SNPs exhibited good uniformity and almost perfect spherical and square shapes. The zeta potential and Fourier transform infrared spectroscopy results confirmed that the SNPs were covered with negative carboxyl groups (zeta potential ranging from -21.8 ±â€¯1.06 to -9.78 ±â€¯0.89 mV). The gelatinization enthalpy of SNPs from PS significantly decreased, changing from 16.63 ±â€¯0.91 to 9.81 ±â€¯0.19 J/g. However, the crystal patterns of SNPs from the WCS and PS after plasma and ultrasonic treatments did not change. The crystallinity of SNPs from PS decreased from 45.2% to 16.5%. This novel approach to preparing SNPs is low cost, simple and green. The developed SNPs could have great potential in the food, biomedical, and material industries.