Synthesis of O‐Acyl Isopeptides

O‐Acyl isopeptides, in which the N‐acyl linkage on the hydroxyamino acid residue (e.g., Ser and Thr) is replaced with an O‐acyl linkage, generally possess superior water‐solubility to their corresponding native peptides, as well as other distinct physicochemical properties. In addition, O‐acyl isopeptides can be rapidly converted into their corresponding native peptide under neutral aqueous conditions through an O‐to‐N acyl migration. By exploiting these characteristics, researchers have applied the O‐acyl isopeptide method to various peptide‐synthesis fields, such as the synthesis of aggregative peptides and convergent peptide synthesis. This O‐acyl‐isopeptide approach also serves as a means to control the biological function of the peptide in question. Herein, we report the synthesis of O‐acyl isopeptides and some of their applications.     

Four New Lariciresinol‐Based Lignan Glycosides from the Roots of Rhus javanica var. roxburghiana

The four new lariciresinol‐based lignan glycosides, (?)‐lariciresinol 4′‐(6″‐O‐feruloyl‐β‐D ‐glucopyranoside) ( 1 ), (?)‐lariciresinol 4′‐(4″,6″‐di‐O‐feruloyl‐β‐D ‐glucopyranoside) ( 2 ), 5,5′‐dimethoxylariciresinol 4′‐(4″,6″‐di‐O‐feruloyl)‐β‐D ‐glucopyranoside) ( 3 ), and 4‐O‐[α‐(1,2‐dihydroxyethyl)syringyl]‐5,5′‐dimethoxylariciresinol 4′‐(4″,6″‐di‐O‐feruloyl‐β‐D ‐glucopyranoside) ( 4 ), together with two known ones, lariciresinol 4′‐β‐D ‐glucopyranoside) ( 5 ) and tortoside B ( 6 ), were isolated from the BuOH extract of Rhus javanica var. roxburghiana roots, and their structures were established by means of various spectroscopic techniques.     

New Phenol Glycosides from the Roots of Rhus Javanica var. Roxburghiana

Two new phenol glycosides, 3,4,5‐trimethoxyphenol‐1‐O‐β‐d ‐glucopyranosyl‐4′,6′‐O‐(E)‐diferuloyl ester ( 1 ), 3,5‐dimethoxy‐4‐hydroxyphenylmethanol‐4‐O‐β‐d ‐glucopyranosyl‐4′,6′‐O‐(E)‐diferuloyl ester ( 2 ), together with six known compounds were isolated from the n‐butanol extract of Rhus javanica var. roxburghiana and their structures were established by various spectroscopic techniques.     

Diversity of Chemical Constituents from Saxifraga Montana H.

A thorough phytochemical investigation of the whole plant of Saxifraga montana H. afforded a new glucoside, methyl 6″‐O‐(E)‐p‐hydroxycinnamoxyl‐glucosyringate ( 1 ), and seventeen known natural products, 3‐methyl‐6‐methoxy‐3,4‐dihydroisocoumarin‐8‐O‐β‐D‐glucospyranoside ( 2 ), gallic acid ( 3 ), glucosyringic acid ( 4 ), daphnoretin ( 5 ), chamaejasmoside ( 6 ), myricetin ( 7 ), quercetin ( 8 ), quercetin‐3‐O‐β‐D‐galactopyranoside ( 9 ), quercetin‐3‐O‐α‐L‐arabinoside ( 10 ), quercetin‐3‐O‐β‐D‐glucospyranoside ( 11 ), rutin ( 12 ), quercetin‐3‐O‐β‐D‐glucopyranosyl (6‐1) glucopyranoside ( 13 ), ursolic acid ( 14 ), 5,28‐stigmastadien‐3β‐ol ( 15 ), β‐sitosterol ( 16 ), β‐daucosterin ( 17 ), 6′‐palmitoxyl‐β‐daucosterin ( 18 ). On the basis of various spectroscopic methods, especially intensive 2D‐NMR (COSY, HMQC and HMBC), FAB‐MS and HR‐ESI‐MS techniques, their structures were elucidated.     

The synthesis and nucleophilic substitution of haloxanthones

Acylation reaction of m‐cresol with 2,6‐dihalobenzoic acid in the presence of methansulfonic acid and subsequently, cyclization of the obtained o‐hydroxybenzophenones with K₂CO₃/dimethyl formamide, afforded haloxanthones 4 and 5 in high yields. Aromatic nucleophilic substitution of the resulted haloxanthones with O‐, N‐ and S‐nucleophiles are studied in a comparative manner, and various new O‐, N‐ and S‐substituted xanthones have obtained.     

Directly Regioselective Protection of Secondary Hydroxyl Group on Ribosides in Aqueous Solution

Selective benzoylation of secondary hydroxyl on sugar moiety of various ribosides including N‐ribosides, O‐ribosides and 2′‐deoxy‐N‐riboside was investigated by using benzoyl chloride and Na₂CO₃ in aqueous CH₃CN. The influence of the aglycone and sugar moiety on the selectivity of benzoylation was discussed as well. A most efficient method for preparation of 2′,3′‐O‐dibenzoylnucleosides was developed.     

Rapid analysis of lignans from leaves of Podophyllum peltatum L. samples using UPLC‐UV‐MS

A new rapid UPLC‐UV‐MS method has been developed that permits the analysis of four lignans (4′‐O‐demethylpodophyllotoxin, podophyllotoxin, α‐peltatin and β‐peltatin) in P. peltatum L. Podophyllotoxin is a natural lignan that is being used as a precursor for the semi‐synthetic anti‐cancer drugs etoposide, teniposide and etopophos. The chromatographic separation was achieved using a reversed‐phase C₁₈ column with a mobile phase of water and acetonitrile, both containing 0.05% formic acid. Analyses of P. peltatum leaves collected from different colonies within a single site indicated a significant variation in 4′‐O‐demethylpodophyllotoxin, α‐peltatin, podophyllotoxin and β‐peltatin content. Within 3.0 min four main lignans could be separated with detection limits of 0.1, 0.3, 0.3 and 0.2 μg/mL, respectively. 4′‐O‐demethylpodophyllotoxin and α‐peltatin appeared most prominently among the lignans obtained. The podophyllotoxin content was found in the range of 0.004–0.77% from 16 samples collected from 6 colonies within the same site. The content of podophyllotoxin is directly proportional to the content of 4′‐O‐demethylpodophyllotoxin and inversely proportional to α‐peltatin and β‐peltatin content. LC‐mass spectrometry coupled with electrospray ionization (ESI) interface method is described for the identification of four lignans in various populations of plant samples. By applying principal component analysis and hierarchical cluster analysis, Podophyllum samples collected from various colonies within a location were distinguished. Copyright © 2011 John Wiley & Sons, Ltd.     

Aniline‐Promoted Cyclization–Replacement Cascade Reactions of 2‐Hydroxycinnamaldehydes with Various Carbonic Nucleophiles through In Situ Formed N,O‐Acetals

In this study, we report the harnessing of new reactivity of N,O‐acetals in an aminocatalytic fashion for organic synthesis. Unlike widely used strategies requiring the use of acids and/or elevated temperatures, direct replacement of the amine component of the N,O‐acetals by carbon‐centered nucleophiles for C?C bond formation is realized under mild reaction conditions. Furthermore, without necessary preformation of the N,O‐acetals, an amine‐catalyzed in situ formation of N,O‐acetals is developed. Coupling both reactions into a one‐pot operation enables the achievement of a catalytic process. We demonstrate the employment of simple anilines as promoters for the cyclization–substitution cascade reactions of trans‐2‐hydroxycinnamaldehydes with various carbonic nucleophiles including indoles, pyrroles, naphthols, phenols, and silyl enol ethers. The process offers an alternative approach to structurally diverse, “privileged” 2‐substituted 2H‐chromenes. The synthetic power of the new process is furthermore shown by its application in a 2‐step synthesis of the natural product candenatenin E and for the facile installation of 2‐substituted 2H‐chromene moieties into biologically active indoles.     

天然产物 6-脱氧-6氨基葡萄糖甘油糖脂的合成

天然氨基甘油糖脂sn-1,2-dipalmitoyl-3-(N-palmitoyl-6-dehydroxy-6-amino-α-glucosyl)glycerol 3 和 sn-1-palmitoyl-2-myristoyl-3-(N-stearoyl-6-dehydroxy-6-amino-α-glucosyl)glycerol 4 通过简便有效的合成策略首次被合成。其关键步骤为：三氯亚胺酯糖基供体 10 与 (S)-isopropyleneglycerol 在乙醚溶液中发生糖苷化反应,立体选择性的生成3-O-(2,3,4-tri-O-benzyl-6-dehydroxy-6-benzyloxycarbonylamino-α-D- glucopyranoyl)-1,2-O-isopropylene-sn- glycerol 7。中间体 7 经过脱除丙酮叉、与不同的脂肪酸缩合、脱除保护基和选择性的在氨基上酰化,最终得到目标化合物 3 和 4。     

Recent advances in methods for the analysis of protein o‐glycosylation at proteome level

O‐Glycosylation, which refers to the glycosylation of the hydroxyl group of side chains of Serine/Threonine/Tyrosine residues, is one of the most common post‐translational modifications. Compared with N‐linked glycosylation, O‐glycosylation is less explored because of its complex structure and relatively low abundance. Recently, O‐glycosylation has drawn more and more attention for its various functions in many sophisticated biological processes. To obtain a deep understanding of O‐glycosylation, many efforts have been devoted to develop effective strategies to analyze the two most abundant types of O‐glycosylation, i.e. O‐N‐acetylgalactosamine and O‐N‐acetylglucosamine glycosylation. In this review, we summarize the proteomics workflows to analyze these two types of O‐glycosylation. For the large‐scale analysis of mucin‐type glycosylation, the glycan simplification strategies including the ‘‘SimpleCell’’ technology were introduced. A variety of enrichment methods including lectin affinity chromatography, hydrophilic interaction chromatography, hydrazide chemistry, and chemoenzymatic method were introduced for the proteomics analysis of O‐N‐acetylgalactosamine and O‐N‐acetylglucosamine glycosylation.     

Iron‐Catalyzed Aminomethyloxygenative Cyclization of Hydroxy‐α‐diazoesters with N,O‐Aminals

A new and efficient cyclization reaction has been developed to synthesize cyclic α,α‐disubstituted β‐amino esters via iron‐catalyzed intramolecular aminomethyloxygenative cyclization of diazo compounds with N,O‐aminal under mild reaction conditions. A broad range of hydroxy‐α‐diazoesters with different substituents and various N,O‐aminals were compatible with this protocol, affording the corresponding α,α‐disubstituted β‐amino esters bearing a five‐ to eight‐membered oxacycle in good yields.     

Megastigmane Glycosides from Docynia indica and Their Anti‐inflammatory Activities

Using various chromatographic methods, three new megastigmane glycosides, docynicasides A – C ( 1  –  3 ) and ten known, (6S,9R)‐vomifoliol 9‐O‐β‐d ‐xylopyranosyl‐(1′′→6′)‐O‐β‐d ‐glucopyranoside ( 4 ), hyperin ( 5 ), quercitrin ( 6 ), quercetin 3‐α‐l ‐arabinofuranoside ( 7 ), naringenin 7‐O‐β‐d ‐glucopyranoside ( 8 ), phloridzin ( 9 ), phloretin 2′‐O‐β‐d ‐xylopyranosyl‐(1→6)‐β‐d ‐glucopyranoside ( 10 ), pinosylvin 3‐O‐β‐d ‐glucopyranoside ( 11 ), tormentic acid ( 12 ), and chlorogenic acid methyl ester ( 13 ) were isolated from the fruits of Docynia indica. Their chemical structures were elucidated by physical and chemical methods. All the isolated compounds were evaluated for the inhibitory activity on NO production in LPS‐stimulated BV2 cells. As the results, compounds 3  –  5 showed significant inhibitory activity on LPS‐stimulated NO production in BV2 cells with the IC₅₀ values ranging from 21.0 to 29.3 μm .     

Selective Reductions of C‐(4,6‐O‐Benzylidene‐β‐d‐glucopyranosyl) Nitromethane

Abstract

The nitromethyl group of C‐(4,6‐O‐benzylidene‐β‐d‐glucopyranosyl) nitromethane was manipulated by various reduction and oxidation methods and further functionalizations into –CH₂NHOH, –CH?NOH, –CN, –CH?O, and –CH₂NHCONH₂, all with retention of the 4,6‐O‐benzylidene group. Certain reduction methods gave rise to a novel secondary amine via an unusual dimeric aminal.     

Phenylpropanoid Esters of Rhamnose from Buddleja asiatica

Four new phenylpropanoid esters of rhamnose, asiatisides A–D, along with the known compounds, buergeriside C₁ ( 5 ), p‐methoxycinnamic acid, ferulic acid, and O‐methylferulic acid were obtained from the aerial parts of Buddleja asiatica Lour by chromatographic methods. The new compounds were elucidated as 3‐O‐acetyl‐4‐O‐(p‐methoxycinnamoyl)‐α‐L ‐rhamnopyranose ( 1 ), 3‐O‐acetyl‐4‐O‐feruloyl‐α‐L ‐rhamnopyranose ( 2 ), 2‐O‐acetyl‐4‐O‐(O‐methylferuloyl)‐α‐L ‐rhamnopyranose ( 3 ), 2‐O‐acetyl‐4‐O‐(p‐methoxycinnamoyl)‐α‐L ‐rhamnopyranose ( 4 ) by spectral data (1D‐, 2D‐NMR, and MS), respectively.     

Intermediates Involved in the Oxidation of Nitrogen Monoxide: Photochemistry of the cis‐N2O2⋅O2 complex and of sym‐N2O4 in Solid Ne Matrices

Pure sym‐N₂O₄ isolated in solid Ne was obtained by passing cold neon gas over solid N₂O₄ at ?115 °C and quenching the resulting gaseous mixture at 6.3 K. Filtered UV irradiation (260–400 nm) converts sym‐N₂O₄ into trans‐ONONO₂, a weakly interacting (NO₂)₂ radical pair, and traces of the cis‐N₂O₂?O₂ complex. Besides the weakly bound ON?O₂ complex, cis‐N₂O₂?O₂ was also obtained by co‐deposition of NO and O₂ in solid Ne at 6.3 K, and both complexes were characterised by their matrix IR spectra. Concomitantly formed cis‐N₂O₂ dissociated on exposure to filtered IR irradiation (400–8000 cm^?1), and the cis‐N₂O₂?O₂ complex rearranged to sym‐N₂O₄ and trans‐ONONO₂. Experiments using ¹⁸O₂ in place of ¹⁶O₂ revealed a non‐concerted conversion of cis‐N₂O₂?O₂ into these species, and gave access to four selectively di‐¹⁸O‐substituted trans‐ONONO₂ isotopomers. No isotopic scrambling occurred. The IR spectra of sym‐N₂O₄ and of trans‐ONONO₂ in solid Ne were recorded. IR fundamentals of trans‐ONONO₂ were assigned based on experimental ^16/18O isotopic shifts and guided by DFT calculations. Previously reported contradictory measurements on cis‐ and trans‐ONONO₂ are discussed. Dinitroso peroxide, ONOONO, a proposed intermediate in the IR photoinduced rearrangement of cis‐N₂O₂?O₂ to the various N₂O₄ species, was not detected. Its absence in the photolysis products indicates a low barrier (≤10 kJ mol^?1) for its exothermic O? O bond homolysis into a (NO₂)₂ radical pair.     

Brauhenefloroside E and F; acylated flavonol glycosides from Stocksia brauhica Linn

Two new acylated flavonol glycosides, 3‐O‐{[2‐O‐β‐D ‐glucopyranosyl]‐3‐[O‐β‐D ‐glucopyranosyl]‐4‐[(6‐O‐p‐coumaroyl)‐O‐β‐D ‐glucopyranosyl]}‐α‐L ‐rhamnopyranosyl‐kaempferol 7‐O‐α‐L ‐rhamnopyranoside and 3‐O‐{2‐[(6‐O‐p‐coumaroyl)‐O‐β‐D ‐glucopyranosyl]‐3‐[O‐β‐D ‐glucopyranosyl]‐4‐[(6‐O‐p‐coumaroyl)‐O‐β‐D ‐glucopyranosyl]}‐α‐L ‐rhamnopyranosyl‐kaempferol 7‐O‐α‐L ‐rhamnopyranoside, trivially named as brauhenefloroside E (1) and F (2), respectively, were isolated from the fruits of Stocksia brauhica and their structures were elucidated using spectroscopic methods, including 2D NMR experiments. Copyright © 2010 John Wiley & Sons, Ltd.     

Immunomodulating Steroidal Glycosides from the Roots of Stephanotis mucronata

Guided by in vitro immunological tests, three immunomodulating steroidal glycosides, stemucronatosides A ( 1 ), B ( 2 ), and C ( 3 ), were isolated from the roots of Stephanotis mucronata. On the basis of chemical evidence and extensive spectroscopic methods including 1D and 2D NMR, their structures were determined as 12‐O‐deacetylmetaplexigenin 3‐[O‐6‐deoxy‐3‐O‐methyl‐β‐D ‐allopyranosyl‐(1→4)‐O‐β‐D ‐cymaropyranosyl‐(1→4)‐β‐D ‐cymaropyranoside], 12‐O‐deacetylmetaplexigenin 3‐[O‐β‐D ‐thevetopyranosyl‐(1→4)‐O‐β‐D ‐cymaropyranosyl‐(1→4)‐β‐D ‐cymaropyranoside], and metaplexigenin 3‐[O‐β‐D ‐glucopyranosyl‐(1→4)‐O‐6‐deoxy‐3‐O‐methyl‐β‐D ‐allopyranosyl‐(1→4)‐O‐β‐D ‐cymaropyranosyl‐(1→4)‐β‐D ‐cymaropyranoside], respectively. These compounds showed immunomodulating activities in vitro.     

Selective Synthesis of 2‐Aryl‐1‐benzylated‐1H‐benzimidazoles

An efficient and simple procedure was developed for the green synthesis of various 2‐aryl‐1‐ben‐zylated‐1H‐benzimidazoles in high yields by condensation of o‐phenylenediamine with aldehydes with P₂O₅/SiO₂ as catalyst under solvent‐free and ambient conditions.     

Flavonol Glycosides from the Leaves of Embelia Keniensis

Five new flavonol glycosides characterized as syringetin 3‐O‐α‐rhamnoside‐7‐O‐β‐glucoside, syringetin 3‐O‐α‐rhamnoside‐7,4′‐di‐O‐β‐glucoside, quercetin‐7‐O‐β‐galactosyl (1→3)‐β‐galactoside, myricetin 3‐O‐α‐rhamnosyl (1→4)‐β‐galactoside and myricetin 3‐O‐β‐glucosyl (1→2)‐β‐glucoside‐7‐O‐β‐glucosyl‐(1→4)‐α‐rhamnoside have been isolated from a methanolic extract of Embelia keniensis leaves. Known flavonols isolated from the same extract included myricetin, quercetin, kaempferol, myricetin 3‐O‐α‐rhamnoside, myricetin 3‐O‐β‐glucoside, quercetin 3‐O‐α‐rhamnoside, quercetin 3‐O‐β‐glucoside, quercetin 3‐O‐β‐xyloside, isorhamnetin 3‐O‐α‐rhamnoside and myricetin 3‐O‐rutinoside. Their structures were established from extensive spectroscopic and chemical studies and by comparison with authentic samples.     

保护的几丁寡糖及结构类似物的合成：复杂氨基寡糖合成的通用方法

建立了逐步合成具有重要生物活性的2-脱氧-2-氨基葡萄糖寡糖链的通用方法。采用邻苯二甲酰基保护氨基、硫代苯基为还原末端的离去基团,以氨基葡萄糖为起始原料,几种保护的几丁寡糖及结构类似物被合成：3-O-乙酰基-4,6-O-亚苄基-2-脱氧-2-邻苯二甲酰亚氨基-b-D-吡喃葡萄糖-（1→4）-（3-O-乙酰基-6-O-苄基-2-脱氧-2-邻苯二甲酰亚氨基）-b-D-吡喃葡萄糖甲苷（4）、3-O-乙酰基-4,6-O-亚苄基-2-脱氧-2-邻苯二甲酰亚氨基-b-D-吡喃葡萄糖-（1→4）-（3-O-乙酰基-6-O-苄基-2-脱氧-2-邻苯二甲酰亚氨基-b-D-吡喃葡萄糖）-（1→4）-（3-O-乙酰基-6-O-苄基-2-脱氧-2-邻苯二甲酰亚氨基）-b-D-吡喃葡萄糖甲苷（6）、3-O-乙酰基-4,6-O-亚苄基-2-脱氧-2-邻苯二甲酰亚氨基-b-D-吡喃葡萄糖-（1→3）-（4,6-O-亚苄基-2-脱氧-2-邻苯二甲酰亚氨基）-b-D-吡喃葡萄糖甲苷（8）、3-O-乙酰基-4,6-O-亚苄基-2-脱氧-2-邻苯二甲酰亚氨基-b-D-吡喃葡萄糖-（1→3）-（4,6-O-亚苄基-2-脱氧-2-邻苯二甲酰亚氨基-b-D-吡喃葡萄糖）- （1→3）-（4,6-O-亚苄基-2-脱氧-2-邻苯二甲酰亚氨基）- b-D-吡喃葡萄糖甲苷（10）。所合成化合物通过核磁共振和质谱分析确证了其化学结构。