对氯醌基碳糖苷的高区域选择性合成方法

本文报道了两条温和、高效、实用的实验室合成对氯代醌基碳糖苷化合物的方法：其一是以芳香碳糖苷1a (1b)为初始原料,在硝酸铵催化下,与N-氯代丁二酰亚胺(NCS)反应获得对氯代芳香碳苷2a (2b),继而经硝酸铈铵(CAN)氧化,得到氯代醌基糖苷3a (3b),总收率为88% (84％);另一路线是通过三甲基氯硅烷在三氟化硼•乙醚作用下对苯醌碳苷4a (4b)的催化加成和水解反应,获得对氯代氢醌基碳苷5a (5b),总收率为82% (76%), 而它与氯代醌基糖苷3a (3b)可以通过氧化与还原反应得以相互转化。     

Umpolung strategy for the synthesis of 2-deoxy-C-aryl glycosides: a serendipitous,efficient route for C-furanoside analogues

[reaction: see text] 2-Deoxy-C-aryl glycosides are potential synthetic targets as they form a very vital moiety of several biologically active natural products. This paper describes a synthetic route using an umpolung strategy, which has not been explored till date. Our synthetic endeavor led to a versatile intermediate aryl ketone 10, which has paved the way for two important classes of C-glycosides, viz., C-alkyl furanosides 12 and methyl 2-deoxy-C-aryl pyranosides 14.     

Neighboring group participation of 9-anthracenylmethyl group in glycosylation: preparation of unusual C-glycosides

[reaction: see text] A coupling of 2-O-arylmethylated D-glucose-derived thioglycosides with various alcohols in the presence of DMTST as an activator is described. The requisite glycosyl donors are efficiently prepared by one-pot procedures. When the aryl groups are phenyl, p-methoxyphenyl, 1-naphthyl, and 2-naphthyl groups, a mixture of alpha- and beta-anomeric O-glycosides is obtained under the conditions, whereas when the aryl group is the 9-anthracenyl group, a highly stereoselective formation of the unusual C-glycosides in good yields via neighboring group participation of the 9-anthracenylmethyl group followed by coupling with a variety of alcohols is observed. Three new chiral centers including a quaternary carbon are created in one single step.     

TESOTf-induced rearrangement of quinols. Efficient construction of the fully functionalized carbon skeleton of the griseusins by a divergent-reconvergent approach

[reaction: see text] The "reverse polarity" or "umpolung" strategy for the total synthesis of aryl C-glycosides was developed in the context of the antibiotic (-)-griseusin B. Although a key reaction in a model sequence for the total synthesis produced two structurally divergent products, both were converted to the same advanced model intermediate that contains the complete carbon skeleton and (except for the extraneous oxygen substituent in the model series) the functional group pattern of the griseusins.     

Access to L- and D-iminosugar C-glycosides from a D-gluco-derived 6-azidolactol exploiting a ring isomerization/alkylation strategy

A flexible synthetic access to six-membered L- and D-iminosugar C-glycosides is reported starting from the easily available 6-azido-6-deoxy-2,3,4-tri-O-benzyl-D-glucopyranose precursor. This methodology involves a highly diastereoselective tandem ring enlargement/alkylation and a stereocontrolled ring contraction. It allows an efficient synthesis of iminosugar C-glycosides displaying structural diversity at both C-1 and C-6.     

A novel and efficient direct aldol condensation from ketones and aromatic aldehydes catalyzed by proline-TEA through a new pathway

A novel and efficient direct aldol condensation from various ketones and a wide range of aldehydes was catalyzed by l-proline-TEA (triethylamine) in MeOH at room temperature, affording the corresponding (E)-α,β-unsaturated ketones in excellent yields. By using the method, some complicated (E)-α,β-unsaturated ketone C-glycosides were obtained from unmodified ketone C-glycosides and aldehydes. This reaction proceeds through a new pathway, in which the specific intermediate was captured and identified.     

A stereocontrolled route to a synthon for the aglycone of the aureolic acids

Cyclohexenone 3, a synthon for the aureolic acid aglycone, has been prepared using D-fucose and trimethylsilyloxybutadiene as starting materials.     

Olivomycin and related antibiotics XXVIII. Monomeric composition of aureolic acid and proof that the antibiotics LA-7017 and mithramycin are identical to it

Summary 1. It has been shown that aureolic acid, antibiotic LA-7017, and mithramycin are identical.2. It has been established that aureolic acid is a glycoside of chromomycinone (I) and contains the monosaccharides D-olivose (II), D-oliose (III), and D-mycarose (IV) in a ratio of 3 : 1 : 1.For Communication XXVII, see [1], and for a preliminary communication see [2].M. M. Shemyakin Institute of the Chemistry of Natural Compounds, Academy of Sciences of the USSR. All-Union Scientific-Research Institute of Antibiotics. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 537–541, July–August, 1972.     

Novel carboranyl C-glycosides for the treatment of cancer by boron neutron capture therapy

The synthesis of the novel unprotected carboranyl C-glycosides 2 and 20-24 starting from ethynyl C-glycosides 1, 5-8, 10, and 13 is described. The new compounds are highly water-soluble and display only a very low cytotoxicity, which makes them promising candidates for use in boron neutron capture therapy for the treatment of cancer.     

Stereoselective Synthesis of C-Glycosides by Suzuki Cross-coupling Reaction

Carbohydrates and their conjugates have been recognized to play a wide variety of metabolic roles in numerous biological processes.[1] Various modified sugars and analogues have been recently synthesized for further investigation of glycosidase reactions and for the development of specific glycosidase inhibitors.[2] As one of the most important carbohydrate mimics, C-glycosides have attracted great attention due to their stability to chemical or enzymatic hydrolysis of the glycosidic linkage. A number of methodologies for the preparation of C-glycosides have been extensively investigated.[3] We have recently reported the syntheses of novel C-glycosyl amino acids and amino-C-disaccharides possessing a ketose form via the stereoselective 1,3-dipolar cycloaddition of exo-methylenesugars (1) and nitrones.[4,5] As a continuation of our research on the synthesis of C-glycosides using exo-methylenesugar as the precursor, we wish to describe here a stereoselective synthesis of C-glycosides by Suzuki cross-coupling reaction.     

Tactics and strategies for the synthesis of iminosugar C-glycosides: a review

Three decades after their first synthesis, iminosugar C-glycosides have become an important class of iminosugars with promising biological and therapeutic properties. The purpose of this review is to provide an overview of the versatile strategies that have been developed to synthesize this family of stable imino-analogues of glycosides and glycoconjugates. Some guidelines and predictive stereoselective models are presented to facilitate the design of synthetic strategies toward iminosugar C-glycosides of defined configuration.     

2,3-Anhydrosugars in glycoside bond synthesis: application to furanosyl azides and C-glycosides

The preparation of 2-deoxy-2-thiotolylfuranosyl azides and C-glycosides from a 2,3-anhydrosugar thioglycoside with the d-lyxo stereochemistry is described. The reaction is performed by treatment of the thioglycoside with a trimethylsilylated nucleophile in the presence of BF₃·OEt₂. This approach provides a convenient route to the preparation of the corresponding 2-deoxy-furanosyl azides and C-glycosides. In contrast, the use of an isomeric substrate, with the 2,3-anhydro-d-ribo stereochemistry, gave these products in low to modest yield.     

Ketopremithramycins and ketomithramycins, four new aureolic acid-type compounds obtained upon inactivation of two genes involved in the biosynthesis of the deoxysugar moieties of the antitumor drug mithramycin by Streptomyces argillaceus, reveal novel insights into post-PKS tailoring steps of the mithramycin biosynthetic pathway

Mithramycin is an aureolic acid-type antimicrobial and antitumor agent produced by Streptomyces argillaceus. Modifying post-polyketide synthase (PKS) tailoring enzymes involved in the production of mithramycin is an effective way of gaining further information regarding the late steps of its biosynthetic pathway. In addition, new "unnatural" natural products of the aureolic acid-type class are likely to be produced. The role of two such post-PKS tailoring enzymes, encoded by mtmC and mtmTIII, was investigated, and four novel aureolic acid class drugs, two premithramycin-type molecules and two mithramycin derivatives, were isolated from mutant strains constructed by insertional gene inactivation of either of these two genes. From data bank comparisons, the corresponding proteins MtmC and MtmTIII were believed to act as a C-methyltransferase involved in the production of the D-mycarose (sugar E) of mithramycin and as a ketoreductase seemingly involved in the biosynthesis of the mithramycin aglycon, respectively. However, gene inactivation and analysis of the accumulated products revealed that both genes encode enzymes participating in the biosynthesis of the D-mycarose building block. Furthermore, the inactivation of MtmC seems to affect the ketoreductase responsible for 4-ketoreduction of sugar C, a D-olivose. Instead of obtaining premithramycin and mithramycin derivatives with a modified E-sugar upon inactivation of mtmC, compounds were obtained that completely lack the E-sugar moiety and that possess an unexpected 4-ketosugar moiety instead of the D-olivose at the beginning of the lower deoxysaccharide chain. The inactivation of mtmTIII led to the accumulation of 4E-ketomithramycin, showing that this ketoreductase is responsible for the 4-ketoreduction of the D-mycarose moiety. The new compounds of the mutant strains, 4A-ketopremithramycin A2, 4A-keto-9-demethylpremithramycin A2, 4C-keto-demycarosylmithramycin, and 4E-ketomithramycin, indicate surprising substrate flexibility of post-PKS enzymes of the mithramycin biosynthetic pathway. Although the glycosyltransferase responsible for the attachment of D-mycarose cannot transfer the unmethylated sugar to the existing lower disaccharide chain, it can transfer the 4-ketoform of sugar E. In addition, the glycosyltransferase MtmGIV, which is responsible for the linkage of sugar C, is also able to transfer an activated 4-ketosugar. The oxygenase MtmOIV, normally responsible for the oxidative cleavage of the tetracyclic premithramycin B into the tricyclic immediate precursor of mithramycin, can act on a substrate analogue with a modified or even incomplete trisaccharide chain. The same is true for glycosyltransferases MtmGI and MtmGII, both of which partake in the formation and attachment of the A-B disaccharide in mithramycin.     

Stereospecific synthesis of alpha- and beta-C-glycosides from glycosyl sulfoxides: scope and limitations

C-Glycosides derived from alpha-L-fuco-, alpha-D-gluco-, beta-D-gluco-, and alpha-D-mannopyranose have been synthesized from the corresponding glycosyl phenyl sulfoxide through phenylsulfinyl-lithium exchange, to generate an anomeric carbanion, and subsequent reaction with a carbon electrophile. The reactions were stereospecific and proceeded with retention of the configuration at the anomeric center. Improved yields of C-glycosides were obtained by an inverse addition protocol. Trapping of the anomeric carbanion with aldehydes gave best results. Reaction with ketones, chloroformates, nitriles, and alkyl halides was also explored. Mechanistic aspects of the reaction are discussed.     

Controlled acid hydrolysis and kinetics of flavone C-glycosides from trollflowers

Acid hydrolysis mechanisms of orientin-2"-O-galactopyranoside(OGA),orientin and other flavone C-glycosides in the trollflowers[Trollius chinensis Bunge) were studied in this report for the first time.Hydrolysis parameters including temperature,acidity,solvent and reaction time were comprehensively investigated.OGA could be hydrolyzed to orientin,followed by an isomerization to isoorientin via a reversible Wessely-Moser rearrangement reaction under stronger acidic conditions.A first-order kinetic model fitted the hydrolysis process of OGA well.Under the optimal hydrolysis conditions of 80 ℃,1.0 mol/L H~+ and 7 h reaction time,about 77%OGA was transformed to orientin with no detectable isoorientin.These results could be helpful for better understanding of the acid hydrolysis kinetics of flavone C-glycosides,as well as the preparation of these valuable components under controlled acid hydrolysis conditions.     

Studies on the synthesis of durhamycin A: stereoselective synthesis of a model aglycone

A stereoselective synthesis of the model aglycone corresponding to the anti-HIV aureolic acids durhamycins A (1) and B (2) is described.     

中药紫花地丁黄酮碳苷类化学成分的超高效液相色谱-电喷雾离子源-四极杆飞行时间串联质谱研究

采用超高效液相色谱-电喷雾离子源-四极杆飞行时间串联质谱(UPLC-ESI-QTOF-MS/MS)方法,以中药紫花地丁中分离得到的5个黄酮碳苷化合物为对照品,研究了黄酮二糖碳苷类化合物在ESI-QTOF-MS/MS质谱中的裂解规律。研究进一步证实了文献报道的黄酮二糖碳苷C-6位取代糖基较C-8位糖更易优先发生裂解;但同时发现结构中如果含有不稳定构象的糖基取代时,该规律不再适用。通过对照品的质谱裂解规律,并结合文献和高分辨质谱数据,成功表征和鉴定了紫花地丁中21个黄酮二糖碳苷类以及4个黄酮氧苷类成分。该方法能快速、灵敏、准确地对中药中微量黄酮碳苷类成分的结构进行表征和鉴定。     

Ultrasound-assisted synthesis of C-glycosides

A significant rate enhancement was observed in the preparation of allyl and allenyl-C-glycosides from glycosyl acetate or methyl O-glycoside precursors when ultrasound irradiation was employed as an energy source. The C-glycosides were obtained in 77-96% yields in <20 min using TMSOTf as promoter. These results show that sonication provides rapid and efficient access to useful C-glycoside-based building blocks.     

Stereoselective synthesis of functionalized precursors of the CDEF and CDE 2,6-dideoxy-tetra- and trisaccharide units of durhamycins A and B

[structure: see text] Highly stereoselective syntheses of functionalized precursors of the CDEF and CDE 2,6-dideoxy-tetra- and trisaccharide units of the anti-HIV aureolic acids durhamycins A and B using 2-deoxy-2-iodo- and 2-deoxy-2-bromopyranosyl donors are described.     

Flüssigkristalle auf kohlenhydratbasis -II. Mesogene 1-C-n-alkyl-2,5-anhydro-1-desoxy-L-iditole

Title compounds (“C-glycosides of pentofuranoses”) with an alkyl chain longer than four carbon atoms constitute a new class of carbohydrate derived thermotropic liquid crystals.