Stereoselective Synthesis of Aryl Cyclopentene Scaffolds by Heck–Matsuda Desymmetrization of 3‐Cyclopentenol

A new enantioselective Heck–Matsuda desymmetrization reaction was accomplished by using 3‐cyclopentenol to produce chiral five‐membered 4‐aryl cyclopentenol scaffolds in good yields and high ee’s, together with some 3‐aryl‐cyclopentanones as minor products. Mechanistically, the hydroxyl group of 3‐cyclopentenol acts as a directing group and is responsible for the cis‐ arrangement in the formation of the 4‐aryl‐cyclopentenols.     

Synthesis of C1–C11 eribulin fragment and its diastereomeric analogues

A practical stereoselective synthesis of the central C1–C10 fragment of eribulin and its two diastereomeric analogues is developed. Our approach relied on the use of l-ascorbic acid as the starting material which allowed accessing a key intermediate with a syn diol moiety (C9 and C10 of eribulin) and a carboxylic ester group. A functionalized six membered lactone having several required hydroxyl groups was then obtained. In a number of steps, the lactone was converted to an intermediate for our key oxa-Michael reaction. A regio- and stereocontrolled intramolecular oxa-Michael reaction completed the synthesis of the C1–11 fragment having a trans-fused tetrahydropyrans with the exact stereochemistry of various hydroxyl groups, as in eribulin.     

Aliphatic Polyethers with Sulfate,Carboxylate, and Hydroxyl Side Groups—Do They Show Anticoagulant Properties?

There is increasing interest in the synthesis of low molecular weight heparin and heparan sulfate mimetic polymers because of their various potential biomedical applications. The functional activity of heparin and heparan sulfate is believed to arise from the presence of a number of functional groups, such as hydroxyl, carboxylate and sulfate groups. The design and synthesis of novel heparin‐mimetic polymers with a particular functionality poses a formidable challenge and requires carefully control of the selective conversion of functional groups on the polymer chain. Here, this study describes a simple and efficient synthetic protocol for the preparation of heparin‐mimetic linear polyglycidol copolymers based on the selective conversion of primary hydroxyl groups to carboxylic acids under ruthenium‐catalyzed selective dehydrogenation in basic aqueous solution. To achieve the anticoagulant activity of these polymers, primary hydroxyl groups are selectively converted to sulfate groups. The anticoagulant activity of the heparin mimics is studied by rotational thromboelastometry using EXTEM and INTEM assays. The environmentally benign process described herein provides an attractive route for the synthesis of heparin‐mimetic polymers with tailored functions such as anticoagulant activity.

     

A flexible approach to (S)-5-alkyl tetramic acid derivatives: application to the asymmetric synthesis of (+)-preussin and protected (3S,4S)-AHPPA

[reaction: see text] A flexible asymmetric approach to 5-alkyl tetramic acid derivatives is described, which is based on the use of 9 as the first synthetic equivalent to chiral nonracemic tetramic acid 5-carbanionic synthon 9b. The existence of the carbanion intermediate 9b was proven by trapping with trimethylchlorosilane. Application of the present method to the synthesis of antifungal alkaloid (+)-preussin, as well as protected (3S,4S)-AHPPA 6, is also described.     

A Simple Synthesis Route for Selectively Methylated β-Cyclodextrin Using a Copper Complex Sandwich Protecting Strategy

This communication reports a novel synthesis route for the preparation of monofunctionalized β-cyclodextrin in a single stage. The approach involves only the in-situ protection of secondary hydroxyl groups as an excellent alternative to the classical procedure involving a series of five steps of protection and deprotection of hydroxyl groups (both primary and secondary ones) belonging to β-cyclodextrin.     

Enantioselective synthesis of cyclopropane aminoalcohols containing quaternary stereogenic centers

Some title compounds have been synthesized in enantiomerically pure form starting from d- or l-glyceraldehyde as chiral precursors. A new synthesis of (+)-(Z)-methanohomoserine, one of the key intermediates employed, is also described. The target molecules are densely functionalized. Thus, in addition to one or two hydroxyl groups on a side-chain, an amino group is attached to a quaternary carbon of the cyclopropane ring, and the fourth substituent of such a stereogenic center contains a halogen atom, an alkyl group, or an alcohol, thioether or ester function. Some of these compounds are useful precursors in the synthesis of new cyclopropane nucleosides.     

Synthesis and reactions of benzopentathiepin having hydroxyl group

The synthesis of benzopentathiepin having a hydroxyl group at the neighboring position of polysulfur ring was performed by demethylation of 6-ethyl-9-methoxybenzopentathiepin with hydrogenbromide. Benzotrithiole having hydroxyl group was not isolated at all. The hydroxyl group was also alkylated with alkyl iodide in the presence of weak base.     

Chiral Amplification during Asymmetric‐Induced Copolymerization of Phenylacetylenes with Tight Cis‐Cisoidal Main Chains

A novel phenylacetylene ( 1 ) having two hydroxyl groups and a chiral pinanyl group together with the other three related phenylacetylenes has been synthesized and (co)polymerized by using an achiral catalytic system. Among the four monomers, only 1 is suitable to the asymmetric‐induced polymerization ( AIP ). Chiral amplification phenomenon is only observed in the copolymerization of 1 with an achiral phenylacetylene having two hydroxyl groups ( 3 ). The tight helical cis‐cisoidal main chain formed by making intramolecular hydrogen bonds between the hydroxyl groups in the copoly( 1 / 3 ) enhances the efficiency of chiral induction and as a result chiral amplification phenomenon is observed during the copolymerization.

     

Advances in Protecting Groups for Oligosaccharide Synthesis

Carbohydrates contain numerous hydroxyl groups and sometimes amine functionalities which lead to a variety of complex structures. In order to discriminate each hydroxyl group for the synthesis of complex oligosaccharides, protecting group manipulations are essential. Although the primary role of a protecting group is to temporarily mask a particular hydroxyl/amino group, it plays a greater role in tuning the reactivity of coupling partners as well as regioselectivity and stereoselectivity of glycosylations. Several protecting groups offer anchimeric assistance in glycosylation. They also alter the solubility of substrates and thereby influence the reaction outcome. Since oligosaccharides comprise branched structures, the glycosyl donors and acceptors need to be protected with orthogonal protected groups that can be selectively removed one at a time without affecting other groups. This minireview is therefore intended to provide a discussion on new protecting groups for amino and hydroxyl groups, which have been introduced over last ten years in the field of carbohydrate synthesis. These protecting groups are also useful for synthesizing non‐carbohydrate target molecules as well.     

A three-component coupling approach to cyclopentanoids.

A new approach to 2,3-disubstituted cyclopentenones has been developed. This approach consists of a two-step protocol involving the cyclization of a Z-vinyl bromide under Barbier type conditions to form a cyclopentenol, which is then oxidatively rearranged to generate the cyclopentenone. The Z-vinyl bromide is in turn derived from a ruthenium catalyzed three-component coupling of an alkyne, an enone, and a HBr equivalent. A range of 2,3-disubstituted cyclopentenones has been generated, including short syntheses of jasmone and dihydrojasmone. Further applicability of this strategy is shown in the total syntheses of tetrahydrodicranenone B, rosaprostol, and a selective COX-2 inhibitor.     

聚苯乙烯基N,O-二酰基磺酰羟胺树脂: 一种双酰基转移试剂在合成酰胺库中的应用

用聚苯乙烯基磺酰羟胺树脂1与酰氯2反应合成了聚苯乙烯基N,O-二酰基磺酰羟胺树脂3. 树脂3作为一种新的双酰基转移试剂可与胺4发生酰基转移反应, 合成了含有24个结构类似的酰胺化合物库. 改变酰氯的种类, 结果发现双对硝基苯甲酰树脂3a的活性较高. 双酰基树脂3胺解结果表明, 由脂肪族胺得到的酰胺收率较芳香族胺高. 当解脱试剂同时含有羟基和氨基时, 双酰基树脂3能选择性地在氨基端发生酰基转移, 而羟基端不受影响.     

The Microwave-assisted Preparation and X-Ray Structure of 3-Bromocarbazole-N-Acetic Acid

Carbazole and its derivatives have attracted the attention due to its photophysical and photochemical properties as well as biological activities1. So far considerable amounts of carbazole derivatives were prepared to probe the nature of electronic states. Among these carbazole derivatives, carbazole-9-carboxylic acids were important intermediates because the carboxylic group is an active function group for further transformation into other functions. The molecular packing modes of carboxylic …     

An efficient approach for total synthesis of aminopropyl functionalized ganglioside GM1b

A highly efficient protocol for the synthesis of aminopropyl functionalized ganglioside GM1b has been described. The full protected ganglioside GM1b was obtained in 71% yield within 5 h. The key feature of the synthetic approach was the use of sialic acid donor that was with a C-5 trichloroacetamide moiety and with a dibenzyl phosphite residue as leaving group at the anomeric carbon. The sialyl donor gave high yields and excellent α-anomeric selectivities with a wide variety of glycosyl acceptors ranging from C-3 or C-6 hydroxyls of galactoside to C-6 hydroxyl of glucosaminoside by using TMSOTf as catalyst in a mixture solution of acetonitrile and methylene chloride.     

Total synthesis of an antitumor antibiotic,Fostriecin (CI-920)

The total synthesis of an antitumor antibiotic, fostriecin (CI-920), via a highly convergent route is described. A characteristic feature of the present total synthesis is that the synthesis was achieved via a coupling procedure of three segments A, B, and C. The unsaturated lactone moiety of fostriecin, corresponding to segment A, was constructed from a known Horner-Emmons reagent, and the stereochemistry of the C-5 position was introduced by asymmetric reduction with (R)-BINAl-H. Segment B having a series of stereogenic centers was synthesized from (R)-malic acid and the stereogenic centers at the C-8 and C-9 positions were prepared by a combination of Wittig reaction and Sharpless asymmetric dihydroxylation reaction. The conjugated Z,Z,E-triene moiety of fostriecin, corresponding to segment C, was eventually constructed by Wittig reaction and Stille coupling reaction. The phosphate moiety, which is known to be essentially important for the antitumor activity, was introduced via two routes: (i) direct phosphorylation of the monohydroxyl derivative in which other hydroxyl groups are protected with silyl groups; (ii) cyclic phosphorylation and selective cleavage of the cyclic phosphate derivative. Although the former route is basically the same as those reported by other groups, the latter route is novel and more effective than the former one. The present total synthesis would serve as a versatile synthetic route to not only fostriecin, but also its various analogues including stereoisomers.     

Toward Libraries of Biotinylated Chondroitin Sulfate Analogues: From Synthesis to In Vivo Studies

Chondroitin sulfate‐E (CS‐E) oligosaccharidic analogues (di to hexa) were prepared from lactose. In these compounds, the 2‐acetamido group was replaced by a hydroxyl group. This modification speeded up the synthesis, and large oligosaccharides were constructed in a few steps from a lactose‐originated block. The protecting groups used were as follows; Fmoc for hydroxyl groups to be glycosylated, allyl group for anomeric position protection, and trichoroacetimidate leaving groups were used to prepare up to octasaccharides. We took advantage of the presence of allyl group to develop a click biotinylation, through its transformation into a 3‐azido‐2‐hydroxyl propyl group in two steps (epoxidation and sodium azide epoxide opening). The biotinylating agent was a water‐soluble propargylated and biotinylated triethylene glycol (PEG). By using surface plasmon resonance (SPR), it was shown that the di‐, tetra‐, and hexasaccharides display a binding affinity and selectivity toward HSF/GSF and CXCL12 similar to that of CS‐E. A parallel study confirmed their mimicry of natural compounds, based on the hexasaccharide interaction with Otx2, a homeodomain protein involved in brain maturation, thus validating our simplification approach to synthesize bioactive GAG.     

Electrochemical Oxidation of Quercetin

The mechanism of electrochemical oxidation of quercetin on a glassy carbon electrode has been studied using cyclic, differential pulse and square‐wave voltammetry at different pH. It proceeds in a cascade mechanism, related with the two catechol hydroxyl groups and the other three hydroxyl groups which all present electroactivity, and the oxidation is pH dependent. Quercetin also adsorbs strongly on the electrode surface; and the final oxidation product is not electroactive and blocks the electrode surface. The oxidation of the catechol 3′,4′‐dihydroxyl electron‐donating groups, occurs first, at very low positive potentials, and is a two electron two proton reversible reaction. The hydroxyl group oxidized next was shown to undergo an irreversible oxidation reaction, and this hydroxyl group can form a intermolecular hydrogen bond with the neighboring oxygen. The other two hydroxyl groups also have an electron donating effect and their oxidation is reversible.     

Does a diol cyclic urea inhibitor of HIV-1 protease bind tighter than its corresponding alcohol form? A study by free energy perturbation and continuum electrostatics calculations

The cyclic urea inhibitors of HIV-1 protease generally have two hydroxyl groups on the seven-membered ring. In this study, free energy perturbation and continuum electrostatic calculations were used to study the contributions of the two hydroxyl groups to the binding affinity and solubility of a cyclic urea inhibitor DMP323. The results indicated that the inhibitor with one hydroxyl group has better binding affinity and solubility than the inhibitor with two hydroxyl groups. Therefore, removal of one hydroxyl group from DMP323 may help to improve the properties of DMP323. This is also likely to be true for other cyclic urea inhibitors. The study also illustrated the difficulty in accurate modeling of the binding affinities of HIV-1 protease inhibitors, which involves many possible protonation states of the two catalytic aspartic acids in the active site of the enzyme.     

Conformation, Inversion Barrier, and Solvent-Induced Conformational Shift in Exo- and Endo/Exo-Calix[4]arenes

Calixarenes 4a and 4b having hydroxyl groups in endo and exo positions and the ethanediyl-bridged exo-calixarene 5a were synthesized by a stepwise strategy. Single-crystal X-ray structures were obtained for 4a and for the exo-calixarene 3d, showing the molecules to exist in the 1,2-alternate conformation which is also found for 4a,b in solution. The inversion barriers of 4a and 4b (10.3 and 10.8 kcal mol(-1)) are similar to that determined for the endo-dihydroxycalixarene 12, indicating that the additional intramolecular hydrogen bond between the exo OH groups does not decrease the flexibility of the molecule. In CDCl(3) solution exo-calixarene 5a adopts a 1,2-alternate conformation with the methyl group at the bridge located in an axial position, while in DMSO-d(6) the conformation adopted is the partial cone. Similar solvent-induced conformational shifts were found for the exo-calixarenes 3b and 3d. MM3 calculations predict that the cone form is the lowest energy conformation of 4 and the exo-calixarenes 3 and 5. The calculations suggest that the conformational preferences of the methyl group at the bridge for either the axial or equatorial positions are in large part determined by the repulsive steric interactions with the hydroxyl groups. The inversion barrier of 4b is satisfactorily reproduced by calculations, which indicate that the rotation of the exo rings is less energetically demanding than the rotation of the endo rings.     

Influence of positional isomers on the macroscale and nanoscale architectures of aggregates of racemic hydroxyoctadecanoic acids in their molecular gel, dispersion, and solid states

Inter/intramolecular hydrogen bonding of a series of hydroxystearic acids (HSAs) are investigated. Self-assembly of molecular gels obtained from these fatty acids with isomeric hydroxyl groups is influenced by the position of the secondary hydroxyl group. 2-Hydroxystearic acid (2HSA) does not form a molecular dimer, as indicated by FT-IR, and growth along the secondary axis is inhibited because the secondary hydroxyl group is unable to form intermolecular H-bonds. As well, the XRD long spacing is shorter than the dimer length of hydroxystearic acid. 3-Hydroxystearic acid (3HSA) forms an acyclic dimer, and the hydroxyl groups are unable to hydrogen bond, preventing the crystal structure from growing along the secondary axis. Finally, isomers 6HSA, 8HSA, 10HSA, 12HSA, and 14HSA have similar XRD and FT-IR patterns, suggesting that these molecules all self-assemble in a similar fashion. The monomers form a carboxylic cyclic dimer, and the secondary hydroxyl group promotes growth along the secondary axis.