A Convenient and Stereospecific Synthesis of (Z)-Benzylidenephthalides

A convencient and stereospecific synthesis of (Z)-benzylidenephthalides, including thunberginol F, from phthalides is described.

A New Dimeric Phthalide from Angelica sinensis

A new dimeric phthalide named Z, Z＇-3.3＇a, 7.7＇a-diligustilide was isolated from the roots of Angelica sinensis. Its structure was determined using spectroscopic methods and X-ray crystallographic diffraction analysis.

Au/FeO_x-TiO_2 as an efficient catalyst for the selective hydrogenation of phthalic anhydride to phthalide

Au/FeOx-TiO2,prepared by deposition-precipitation method,is an efficient and stable catalyst for the liquid phase selective hydrogenation of phthalic anhydride to phthalide under mild reaction conditions.

TsOH·H₂O-Catalyzed Friedel-Crafts of Indoles of 3-Hydroxyisobenzofuran-1(3<i>H</i>)-One with Indoles: Highly Synthesis of 3-Indolyl-Substituted Phthalides

An efficient and facile method for the synthesis of 3-indolyl-substituted phthalides by Friedel-Crafts alkylation of indoles with 3-hydroxyisobenzofuran-1(3H)-one has been developed. Using only 2 mol-% TsOH·H2O as the catalyst, various substituted indoles can react smoothly at room temperature to give the corresponding phthalides products in good to excellent yields (up to 96%).

Effect of butyl phthalide on serum cytokines, soluble apoptosis factors and antioxidant molecules in patients with vascular dementia

Objective:To study the effect of butyl phthalide on serum cytokines, soluble apoptosis factors and antioxidant molecules in patients with vascular dementia. Methods:86 patients with vascular dementia admitted in our hospital between January 2014 and January 2016 were selected for retrospective study and divided into observation group and control group (n=43) according to double-blind randomized control. Observation group received butyl phthalide capsule (0.2 g/time, 3 times/d) treatment on the basis of conventional treatment, control group received conventional treatment alone, and both lasted for 24 weeks. After 24 weeks of treatment, ELISA was used to determine serum levels of vascular repair factors and soluble apoptosis factors of two groups of patients, and radioimmunoassay was used to determine serum levels of antioxidant molecules. Results:After 24 weeks of treatment, serum vascular repair factors heme oxygenase-1 (HO-1), angiogenin I (AngI) and vascular endothelial growth factor (VEGF) levels of observation group were higher than those of control group, matrix metalloproteinase-9 (MMP-9) level was lower than that of control group, and differences between groups were statistically significant (P<0.05);serum soluble factor-related apoptosis (sFas) and soluble factor-related apoptosis ligand (sFasL) levels were lower than those of control group (P<0.05);serum antioxidant molecules superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (TAC), catalase (CAT), glutathione S-transferase (GST) and glutathione reductase (GR) levels were higher than those of control group (P<0.05). Conclusions:Butyl phthalide can prompt vascular repair in patients with vascular dementia, and also inhibit apoptosis process and balance the body’s oxidation/antioxidation system function.

Virtual Evaluation on the Activities of Phthalides and Terpenoids from Angelica sinensis

Objective To elucidate potential activities of phthalides and terpenoids from Angelica sinensis by theoretical docking calculation. Methods Eleven components of phthalides and terpenoids were selected as ligand. The crystalline structures of targets related to common diseases were used as the receptors for calculation. The calculations were conducted with Schr?dinger software package. The grading standard of selectivity was developed according to G-score between ligands and receptors. Results Selective targets of phthalides and terpenoids were related to nevous system diseases, cancer, pain, diabetes, cardiovascular disease, liver cirrhosis, nephrotic syndrome, inflammatory diseases, rheumatoid arthritis, dermatosis, leukemia, microbial inflections, immune diseases, and hypercholesterolemia. In addition to the medical treatments reported in the literature, our research also indicated that these two classes of compounds may be used for tumor, diabetes, rheumatoid arthritis, dermatosis, leukemia, liver cirrhosis, and nephrotic syndrome. According to our research, the effects of phthalides and terpenoids may be not so strong. Conclusion The effects of phthalides and terpenoids on diseases founded through virtual evaluation accord greatly with those reported in experiment and clinic. The combination of computer-aided drug evaluation technique and experiment is definitely an important and fast way to investigate the effects and mechanisms of traditional Chinese medicine.

(±)-6-3’a,7-6’-Isowallichilide:A pair of enantiomeric phthalide dimers from Ligusticum chuanxiong with new 6-3’a,7-6’ dimerization sites

(+)-6-3’a,7-6’-Isowallichilide and(-)-6-3’a,7-6’-isowallichilide,a pair of enantio meric phthalide dimers featuring new 6-3’a,7-6’dimerization sites,were isolated from Ligusticum chuanxiong.The structures were elucidated by NMR spectroscopy and X-ray diffraction analysis.Furthermore,the absolute configurations were assigned using experimental and theoretical electronic circular dichroism methods.Their nitric oxide inhibition,antiplatelet aggregation and antioxidant activities were investigated.

Quinine-derived thiourea promoted enantioselective Michael addition reactions of 3-substituted phthalides to maleimides

A highly diastereoselective and enantioselective Michael addition/desymmetrization reaction of maleimides with prochiral 3-substituted phthalides catalyzed by quinine-derived bifunctional thiourea was realized. A broad range of the 3,3′-disubstituted phthalides bearing vicinal quaternary-tertiary stereogenic centers were synthesized in moderate to good yields(up to 96%) with high diastereoselectivities(up to >19:1 dr) and enantioselectivities(up to 96:4 er).

Ruthenium (II)-catalyzed synthesis of phthalides via the cascade addition and cyclization of aromatic acids with aldehydes

The ruthenium-catalyzed intermolecular cascade cyclization of aromatic acids with aromatic aldehydes, which involves the direct insertion of C–H bond into a polar C=O bond and the successive intramolecular nucleophilic substitution, was developed for the synthesis of 3-substituted phthalides in good to excellent yields. This one-pot procedure characterizes in a short reaction time, the cheaper Ru(II) as a catalyst, readily available acids and aldehydes as starting materials, and water as the only theoretical by-product.These merits make the protocol an efficient and cost-effective route for the synthesis of 3-substituted phthalides.

Novel Hydroperoxides of 1-Imino-3,3-Disubstituted-1,3-Dihydro Isobenzofuran

Some 1-imino-3,3-disubstituted-1,3-dihydro isobenzofuran and 2-(1,1-disubstituted hydroxymethyl) benzamide derivatives have been obtained by the aminolysis of phthalide in the presence of triethylamine/aluminum chloride. 1-Benzylimino-3,3-disubstituted-1,3-dihydro isobenzofuran can be peroxidized to the corresponding hydroperoxides on exposure to the air for a long period. The structure was characterized by single crystal X-ray diffraction and the possible mechanism was suggested.

Synthesis and Crystal Structure of Ethyl 4-(2-Chloro-4-fluorophenyl)-6-hydroxy-3-oxo-1,3-dihydro-5-isobenzofurancarboxylate

The crystal structure of the title compound（C17H12ClFO5,Mr=350.72） was determined by single-crystal X-ray diffraction.The crystal belongs to monoclinic,space group P21/c,with a=7.693（1）,b=15.767（1）,c=12.986（1）,β=97.23（1）°,V=1562.6（2）3,Z=4,Dc= 1.491 g/cm3,λ（MoKα）=0.71073,F（000）=720,μ（MoKα）=0.280 mm-1,R=0.0563 and wR=0.1674.A total of 3592 unique reflections were collected,of which 2462 with Ⅰ＆gt;2σ（Ⅰ） were observed.Five-membered lactone rings and hydroxyl-substituted phenyl rings are approximately coplanar with their dihedral angle of 4.1°. The dihedral angle between two different phenyl rings is 71.3°. To our interest, intramolecular O（1）-H（1）…O（4） hydrogen bonds could be found in each molecule. Intramolecular hydrogen bonds and intermolecular van der Waals force contribute to the stability of the structure.

Phytochemical progress made in investigations of Angelica sinensis(Oliv.) Diels

The phytochemical progress on Angelica sinensis(Oliv.) Diels over the past decades is summarized. Since 1970 s, 165 chemical constituents, including phthalides, phenylpropanoids, terpenoids and essential oils, aromatic compounds, alkaloids, alkynes, sterols, fatty acids, and polysaccharides have been isolated or detected from the various parts of the title plant.

Fingerprinting Analysis of Rhizoma Chuanxiong of Commercial Types using ~1H Nuclear Magnetic Resonance Spectroscopy and High Performance Liquid Chromatography Method

The ^1 H nuclear magnetic resonance （^1 H NMR） fingerprints of fractionated non-polar extracts （control substance for a plant drug （CSPD） A） from Rhizoma chuanxiong, the rhizomes of Ligusticum chuanxiong Hort., of seven specimens from different sources were measured on Fourier Transform （FT）-NMR spectrometer and assigned by comparing them with the ^1 H NMR spectra of the isolated pure compounds. The ^1 H NMR fingerprints showed exclusively characteristic resonance signals of the major special constituents of the plant. Although the differences in the relative intensity of the ^1H NMR signals due to a discrepancy in the ratio of the major constituents among these samples could be confirmed by high performance liquid chromatography analysis, the general features of the ^1H NMR fingerprint established for an authentic sample of the rhizomes of L. chuanxiong e. hibited exclusive data from those special compounds and can be used for authenticating L. Chuanxiong species.

Eleven Absorbed Constituents and 91 Metabolites of Chuanxiong Rhizoma Decoction in Rats

Objective:Chuanxiong Rhizoma(CR,the dried rhizomes of Ligusticum chuanxiong)is a well-known traditional Chinese medicine that promotes qi to activate blood,dispels wind,and relieves pain.To date,more than 118 constituents of CR have been isolated and identified.However,the in vivo mechanism of CR decoction is unclear and needs further investigation.In addition,to clarify the effective forms of CR,it is essential to reveal the absorbed constituents and metabolites of CR.Materials and Methods:The absorbed constituents and metabolites in urine and plasma samples of rats orally administered with CR decoction were screened and characterized using a high-performance liquid chromatography with diode array detector and combined with electrospray ionization ion trap time-of-flight multistage mass spectrometry technique.Results:In total,102 compounds,including 11 absorbed constituents(eight phthalides and three phthalic acids)and 91 metabolites(71 phthalide-related and 20 phenolic acid-related),were detected in drug-containing rat urine and plasma samples,among which 33 were new metabolites of either CR or its constituents.Based on the structures of these metabolites,six phthalides(ligustilide,senkyunolide I/H,senkyunolide J/N,and butylidenephthalide)and three phenolic acids(ferulic acid,isoferulic acid,and caffeic acid)were proposed as their precursors.They were also deduced to be the main absorbed constituents of CR decoction,which should have closer relationships with its pharmacological effects than other constituents.Phthalide-related metabolites were formed through the metabolic reactions of hydration,hydroxylation,cysteine conjugation,acetylcysteine conjugation,methanethiol conjugation,mercaptomethanol conjugation,glucuronidation,and sulfation,whereas the phenolic acid-related metabolites were mainly formed by glucuronidation and sulfation.Conclusions:Six phthalides and three phenolic acids were shown to be the main precursors of the metabolites of CR,and 33 compounds were new metabolites of either CR or its constituents.These results are helpful for further understanding of the in vivo mechanism and effective forms of CR.