Umbelliferose Isolated from Cuminum cyminum L. Seeds Inhibits Antigen-Induced Degranulation in Rat Basophilic Leukemia RBL-2H3 Cells

Cuminum cyminum L. (cumin) is an annual plant of the Umbelliferae family native to Egypt. We previously showed that the aqueous extract of cumin seeds suppresses degranulation by downregulating the activation of antigen-induced intracellular signaling molecules in rat basophilic leukemia RBL-2H3 cells. However, the active substances in the extract have not yet been identified. Accordingly, herein, we aimed to ascertain the water-soluble substances present in cumin seeds that inhibit degranulation, which led to the identification of umbelliferose, a characteristic trisaccharide present in plants of the Umbelliferae family. Our study is the first to reveal the degranulation-suppressing activity of umbelliferose, and quantification studies suggest that cumin seed powder contains 1.6% umbelliferose. Raffinose, an isomer of umbelliferose, was also found to significantly suppress antigen-induced degranulation, but less so than umbelliferose. Both umbelliferose and raffinose contain sucrose subunits in their structures, with galactose moieties bound at different sites. These differences in structure suggest that the binding of galactose to the sucrose subunit at the α1-2 bond contributes to its strong degranulation-inhibiting properties.     

Intramolecular 1,3‐Dipolar Cycloaddition‐Mediated Stereoselective Synthesis of Disubstituted Cyclopentane: A Simple Model for the Cyclopentane Ring System of Polycyclic Oroidine Alkaloids

We present a diastereoselective synthesis of disubstituted cyclopentane 8 having a nitrogen‐containing quaternary carbon center, which is found in axinellamine A ( 5 ) and related compounds. During this work, we found that the 1,3‐dipolar cycloaddition product 24 immediately underwent intramolecular redox reaction at the newly formed morpholin‐2‐one moiety, thus affording disubstituted cyclopentane containing a tertiary amine ( 9 ) stereoselectively in good yield. The amine 9 was successfully converted into guanidine 31 , which corresponds to 8 , through iminium cation–enamine isomerization.     

Convenient Method for Dehalogenation of Aryl Halides

Reductive dehalogenation of aryl halides was achieved using hydrogen and a palladium catalyst. By using deuterium gas, the deuterated arenes were readily prepared.     

Synthetic Studies on Sialoglycoconjugates 70: Synthesis of Sialyl and Sulfo Lewis × Analogs Containing a Ceramide or 2-(Tetradecyl)hexadecyl Residue

Abstract

Four sialyl and sulfo Le^x analogs containing glucose in place of N-acetylglucosamine, and a ceramide or 2-(tetradecyl)hexadecyl residue, have been synthesized. Condensation of O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto-2-nonulopyranosylonate)-(2→3)-O-(4-O-acetyl-2,6-diO-benzoyl-β-d-galactopyranosyl)-(1→4)-O-[(2,3,4-tri-O-acetyl-α-L-fucopyranosyl)-(1→3)]-2,4-di-O-benzoyl-α-d-glucopyranosyl trichloroacetimidate (1) with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3, diol (2) or 2-(tetradecyl)-hexadecyl-1-ol (3) gave the corresponding β-glycosides 4 and 7. Compound 4 was converted into the ganglioside 6 via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and saponification of the methyl ester group. Hydrolysis of the O-acyl groups in 7 followed by saponification of the methyl ester, gave sialyl Le^x ganglioside analog 8 containing a branched fatty alkyl residue. On the other hand, glycosylation of O-(4-O-acetyl-2,6-di-O-benzoyl-3-O-levulinyl-β-d-galactopyranosyl)-(1→4)-[O-(2,3,4-tri-O-acetyl-α-L-fucopyranosyl)-(1→3)]-2,6-di-O-benzoyl-α-d-glucopyranosyl trichloroacetimidate (13), prepared from 2-(trimethylsilyl)ethyl O-(2,6-di-O-benzoyl-β-d-galactopyranosyl)-(1→4)-O-[(2,3,4-tri-O-benzyl-α-L-fucopyranosyl)-(1→3)]-2,6-di-O-benzoyl-β-d-glucopyranoside (9) via selective 3-O-levulinylation, acetylation, removal of the 2-(trimethylsilyl)ethyl group, with 2 or 3, gave the desired β-glycosides 14 and 19. Selective reduction of the axido group in 14 followed by coupling with octadecanoic acid gave the ceramide derivative 16. Removal of the levulinyl group in 16 and 19, treatment with sulfur trioxide pyridine complex and subsequent hydrolysis of the protecting groups yielded the corresponding sulfo Le^x analogs 18 and 21.     

Synthetic Studies on Sialoglycoconjugates 12: Total Synthesis of Sialyl Neolactotetraosyl Ceramide

Abstract

Sialoglycoconjugates such as glycoproteins and glycolipids are present as components of cell memberanes and play important roles^1,2 in biological systems. Sialyl neolactotetrasyl ceramide (IV³NeuAcnLc₄Cer), a complex type of ganglioside, was isolated as the major ganglioside of human erythrocytes³ and was shown to be a receptor of that this glycolipid induces granulocytic differentiation of human premyelocytic leukemia cell.     

A p‐Quinodimethane‐Bridged Porphyrin Dimer

A p‐quinodimethane (p‐QDM)‐bridged porphyrin dimer 1 has been prepared for the first time. An unexpected Michael addition reaction took place when we attempted to synthesize compound 1 by reaction of the cross‐conjugated keto‐linked porphyrin dimers 8 a and 8 b with alkynyl/aryl Grignard reagents. Alternatively, compound 1 could be successfully prepared by intramolecular Friedel–Crafts alkylation of the diol‐linked porphyrin dimer 14 with concomitant oxidation in air. Compound 1 shows intense one‐photon absorption (OPA, λ_max=955 nm, ε=45400 M ^?1 cm^?1) and a large two‐photon absorption (TPA) cross‐section (σ⁽²⁾_max=2080 GM at 1800 nm) in the near‐infrared (NIR) region due to its extended π‐conjugation and quinoidal character. It also exhibits a short singlet excited‐state lifetime of 25 ps. The cyclic voltammogram of 1 displays multiple redox waves with a small electrochemical energy gap of 0.86 eV. The ground‐state geometry, electronic structure, and optical properties of 1 have been further studied by density functional theory (DFT) calculations and compared with those of the keto‐linked dimer 8 b . This research has revealed that incorporation of a p‐QDM unit into the porphyrin framework had a significant impact on its optical and electronic properties, leading to a novel NIR OPA and TPA chromophore.     

α-Trifluoromethyl Chalcones as Potent Anticancer Agents for Androgen Receptor-Independent Prostate Cancer

α-Trifluoromethyl chalcones were prepared and evaluated for their antiproliferative activities against androgen-independent prostate cancer cell lines as well as five additional types of human tumor cell lines. The most potent chalcone 5 showed superior antitumor activity in vivo with both oral and intraperitoneal administration at 3 mg/kg. Cell-based mechanism of action studies demonstrated that 5 induced cell accumulation at sub-G1 and G2/M phases without interfering with microtubule polymerization. Furthermore, several cancer cell growth-related proteins were identified by using chalcone 5 as a bait for the affinity purification of binding proteins.     

Serine‐Selective Aerobic Cleavage of Peptides and a Protein Using a Water‐Soluble Copper–Organoradical Conjugate

The site‐specific cleavage of peptide bonds is an important chemical modification of biologically relevant macromolecules. The reaction is not only used for routine structural determination of peptides, but is also a potential artificial modulator of protein function. Realizing the substrate scope beyond the conventional chemical or enzymatic cleavage of peptide bonds is, however, a formidable challenge. Here we report a serine‐selective peptide‐cleavage protocol that proceeds at room temperature and near neutral pH value, through mild aerobic oxidation promoted by a water‐soluble copper–organoradical conjugate. The method is applicable to the site‐selective cleavage of polypeptides that possess various functional groups. Peptides comprising D ‐amino acids or sensitive disulfide pairs are competent substrates. The system is extendable to the site‐selective cleavage of a native protein, ubiquitin, which comprises more than 70 amino acid residues.