Synthesis of a Polymer-bound Sensitizer and its Application in the Photoisomerization of trans-Vitamin D_3 to cis-Vitamin D_3

The photochemistry of the vitamin D family and their precursors has been the subject of extensive studies for many years1-4. Most of the studies focus on the photoisomer- ization of 7-dehydrocholesterol and that of tachysterol to previtamin D3, which is of commercial importance in the synthesis of vitamin D34, 5. Recently the cis/trans isomerization of vitamin D analogs (Scheme 1) draws attention because of its importance in the synthesis of hydroxylated vitamin D metabolites6. However, o…     

Synthesis of γ-Substituted Alcohol with Polymer-bound Amide

With solid phase organic synthesis method(SPOS), polymer-bound N-enoylprolinol(4) was prepared by the attachment of N-enoylprolinol(3) to Merrifield resin and was used for asymmetric Michael additions for the first time. The enantiomeric excess obtained by this method is increased as compared with that obtained by the corresponding solution phase reactions.     

Synthesis of γ-Substituted Alcohol with Polymer-bound Amide

With solid phase organic synthesis method(SPOS), polymer-bound N-enoylprolinol(4) was prepared by the attachment of N-enoylprolinol(3) to Merrifield resin and was used for asymmetric Michael additions for the first time. The enantiomeric excess obtained by this method is increased as compared with that obtained by the corresponding solution phase reactions.     

Synthesis of Silica-anchored Sensitizer and its Application in the Preparation of Previtamin D3 from Tachysterol

A silica gel-anchored photosensitizer was synthesized with anthracene as sensitizer moiety. The photoisomerization of tachysterol to previtamin D3 was carried out with this heterogeneous photosensitizer in ethanol. The experiment results demonstrate that this solid phase photosensitizer is efficient for the photoisomerization and can be simply separated from the reaction mixture by filtration.     

Synthesis of a polymer-bound galactosylamine and its application as an immobilized chiral auxiliary in stereoselective syntheses of piperidine and amino acid derivatives

A 2,3,4-tri-O-pivaloylated beta-D-galactopyranosyl azide bearing a hydroxy-functionalized spacer unit at the C-6 position of the galactose was synthesized and immobilized on the solid phase by using a polymer-bound chlorosilane. The azide was reduced to the corresponding galactopyranosylamine, which served as a versatile chiral auxiliary in highly diastereoselective Ugi four-component condensation reactions at ambient temperature. Fluoride-induced cleavage from the polymeric support furnished N-glycosylated N-acylated alpha-amino acid amides. The reaction of the immobilized galactosylamine with aldehydes gave rise to the corresponding aldimines, which underwent a domino Mannich-Michael condensation reaction with Danishefsky's diene at ambient temperature to yield 2-substituted 5,6-didehydropiperidin-4-ones on the solid phase. Subsequent cleavage with tetra-n-butylammonium fluoride delivered the N-glycosylated products in high yields, purities, and diastereoselectivities. A chemoselective 1,4-hydride addition to the polymer-bound dehydropiperidinones was achieved in the presence of the bulky oxygenophilic Lewis acid methylaluminum [bis(2,6-di-tert-butyl-4-methylphenoxide)]. The conjugate addition of cyano-modified Gilman reagents to the immobilized dehydropiperidinones furnished 2,6-cis-substituted piperidine derivatives as the major diastereomers that were isolated after cleavage from the support.     

Polyethylene as a nonvolatile solid cosolvent phase for catalyst separation and recovery

The studies described here show that a relatively low molecular weight, narrow polydispersity polyethylene (PE) wax (Polywax) can serve as a nontoxic and nonvolatile alternative to alkane solvents in monophasic catalytic organic reactions where catalysts and products are separated under biphasic conditions. In this application, a polymer that is a solid at room temperature substitutes for a conventional alkane solvent at ca. 80 °C. In addition to the advantages of being a nonvolatile, nontoxic, reusable solvent, this hydrocarbon polymer solvent, like heptane, can sequester nonpolar soluble polymer-bound catalysts after a reaction and separate them from products. The extent of this separation and its generality were studied using polyisobutylene (PIB)- and poly(4-dodecylstyrene)-bound dyes and PE-bound Pd allylic substitution catalysts, PIB-bound Pd cross-coupling catalysts, and PE- and PIB-bound metathesis catalysts. Catalytic reactions were effected using single-phase reaction mixtures containing Polywax with toluene, THF, or THF/DMF at ca. 80 °C. These solutions either separate into two liquid phases on addition of a perturbing agent or separate as a solid/liquid mixture on cooling. The hydrocarbon polymer-bound dyes or catalysts either separate into the hot liquid Polywax phase or coprecipitate with Polywax and are subsequently isolated as a nonvolatile Polywax solid phase that contains the dye or the recyclable catalyst.     

Solution- and solid-phase synthesis of radicicol (monorden) and pochonin C

A modular synthesis for pochonin C and radicicol is reported. The two natural products were prepared in seven and eight steps, respectively, from three readily available fragments. Alternative syntheses of these compounds were achieved using a combination of polymer-bound reagents and solid phase reactions. The conformation of the two natural products was studied and compared by using 2D NMR spectroscopy.     

Solid-phase synthesis of substituted alkynes using the Nicholas reaction

The first example of a Nicholas reaction on solid phase is reported, involving the reaction of cobalt complexes of polymer-bound alkynols with different nucleophiles in the presence of a Lewis acid, to form carbon-oxygen or carbon-carbon bonds.     

昆虫性信息素的固相合成

本综述阐明昆虫性信息素固相合成的最新成就。C.C.Leznoff 开创了昆虫性信息素的固相合成,并合成了一系列信息素。他以二醇为原料,以聚合物三苯甲基氯为保护剂。陈德恒等将保护剂改成聚合物三苯甲基氯硅烷,产率比前人有所提高。陈家威等大大改进了前两人的线路,简化了步骤,只抓住关键的一步进行固相合成,总产率比前人提高得更多。     

Carbon-carbon and carbon-heteroatom bond formation on solid phase using cationic iron carbonyl complexes

Iron-mediated methodology for the formation of carbon-carbon and carbon-heteroatom sp(3) bonds on solid phase has been developed. Treatment of a polymer-bound cationic iron cyclohexadienyl complex with carbon, oxygen, nitrogen, and phosphorus nucleophiles, followed by cleavage with amines and subsequent decomplexation, yielded 18 different cyclohexadienoic acid amides of high purity. [reaction: see text]     

First direct lithiation of 2-pyridylpiperazine on solid phase

[reaction: see text] The first direct lithiation of a pyridine derivative on solid phase has been realized. Metalation of polymer-bound 2-pyridylpiperazine with the BuLi-LiDMAE reagent followed by electrophilic quenching and subsequent cleavage provided a range of new useful C-6 substituted 2-piperazinylpyridines.     

Traceless solid-phase synthesis of hydroxylated cyclopentenones

Intramolecular nitrone-alkene cycloadditions on solid phase can be performed using polymer-bound hydroxylamine. Condensation of this reagent with sugar derived 4-pentenals followed by N-O cleavage, quaternization of the amine thus produced, and finally oxidative elimination of the amino group detaches the chiral hydroxylated cyclopentenones from the polymer. The natural antibiotic pentenomycin I was prepared in this way.     

Pyrene-benzoylthiophene bichromophores as selective triplet photosensitizers

Combination of the pyrene and benzoylthiophene units constitutes an interesting approach to design bichromophoric photosensitizers with increased intersystem crossing quantum yield and enhanced selectivity. The potential of this strategy has been illustrated in the present work by using a model photoisomerization reaction.     

Solid supported active esters as linkers: modification of reactivity using iron carbonyl complexes

The reactivity of three polymer-bound cyclohexadienoic acid active esters was modified by complexation with iron tricarbonyl in order to evaluate their potential use as linker systems for solid phase chemistry. The best results were obtained with the tetrafluorophenol ester, which was slowly cleaved when 1 equiv of amine was used, but could be rapidly cleaved with up to 94% yield when the amount of nucleophile was increased.     

Eradication of Gram‐Positive and Gram‐Negative Bacteria by Photosensitizers Immobilized in Polystyrene

Immobilization of photosensitizers in polymers opens prospects for their continuous and reusable application. Methylene blue (MB) and Rose Bengal were immobilized in polystyrene by mixing solutions of the photosensitizers in chloroform with a polymer solution, followed by air evaporation of the solvent. This procedure yielded 15–140 μm polymer films with a porous surface structure. The method chosen for immobilization ensured 99% enclosure of the photosensitizer in the polymer. The antimicrobial activity of the immobilized photosensitizers was tested against Gram‐positive and Gram‐negative bacteria. It was found that both immobilized photosensitizers exhibited high antimicrobial properties, and caused by a 1.5–3 log₁₀ reduction in the bacterial concentrations to their total eradication. The bactericidal effect of the immobilized photosensitizers depended on the cell concentration and on the illumination conditions. Scanning electron microscopy was used to prove that immobilized photosensitizers excited by white light caused irreversible damage to microbial cells. Photosensitizers immobilized on a solid phase can be applied for continuous disinfection of wastewater bacteria.     

Soluble polymer-supported catalysts containing azo dyes

[structure: see text] Azo benzene derivatives were incorporated into soluble polymer-bound catalysts by two different approaches. The first was to attach the dye to the polymer-bound catalysts, using the dye as an innocent spectator to study the phase preference, concentration, and recoverability of a catalyst. The second approach used an azo dye as a ligand to form an effective soluble polymer-bound Pd(II) catalyst for Heck reactions.     

O2/n2-separation by polymer-bound cobalt complexes

Facilitated or complexation-mediated transport of oxygen in the solid membrane containing a fixed carrier was described, by using the polymer-bound cobalt Schiff's base chelate (CoS) and cobaltporphyrin (CoP). α³ β-Substituted cobaltporphyrin derivatives were synthesized: The oxygen-binding reaction to cobalt was affected by the cavity structure on porphyrin, i.e., unbulky amido-substituted groups such as acetylamido- and acrylamido-substituents enhanced oxygen-binding and -dissociation rate constant or provided an oxygen-binding pathway. Oxygen transport through the membranes of these polymer-bound CoP derivatives was selectively augmented due to the rapid and reversible oxygen-binding. Diffusion constants via the fixed CoPs correlated to the characteristics of oxygen-binding reaction.     

Characterization of organic substrates bound to cross-linked polystyrenes by 13C NMR spectroscopy

The ¹³C NMR spectra of a wide variety of organic substrates bound to 2% cross-linked polystyrenes may be obtained routinely, provided the resins can be sufficiently swollen. The ¹³C chemical shifts of polymer-bound trityl alcohol, polymer-bound monotrityl ethers of the symmertrical diols HO (CH₂)_nOH (n=2, 4, 6, 7, 9 and 10), and some related intermediates in the solid phase synthesis of insect pheromones are presented. ¹³C shift additivity correlations, differing little from those in free trityl ethers, are drawn.     

Solid-phase synthesis of 5-amino-1-(substituted thiocarbamoyl)pyrazole and 1,2,4-triazole derivatives via dithiocarbazate linker

A general method is reported for the parallel solid-phase synthesis of 5-amino-1-(substituted thiocarbamoyl)pyrazole and 1,2,4-triazole derivatives based on the cyclization of polymer-bound dithiocarbazate 3 with various electrophiles, such as 3-ethoxyacrylonitriles 8 and cyanocarboimidates 9. The polymer-bound dithiocarbazate 3, produced by nucleophilic reaction with carbon disulfide and Fmoc-hydrazine on the Merrifield resin, served as the key intermediate for subsequent heterocycle diversification. Further nucleophilic substitution on these polymer-bound 5-amino-1-dithiocarboxypyrazoles 4 and 1,2,4-triazoles 6 with various amines under thermal cleavage condition produced the desired 5-amino-1-(substituted thiocarbamoyl)pyrazoles 5 and 1,2,4-triazoles 7. The progress of reactions could be monitored as polymer-bound intermediates by ATR-FTIR spectroscopy on single bead. The final compounds, obtained in good four-step overall yields and high purities upon cleavage from the resins, were characterized by LC/MS, 1H NMR, and 13C NMR spectroscopy.     

Solid-phase development of chiral phosphoramidite ligands for enantioselective conjugate addition reactions

The development of a method for the optimization of chiral ligands for the steric steering of enantioselective Cu-catalyzed conjugate additions of Znalkyls to enones is described. The method is based on combinatorial principles and solid-phase techniques. It includes the combinatorial synthesis of chiral bispidine-derived ligands embodying a phosphoramidite group on the solid phase and their investigation in immobilized form in the conjugate addition of ZnEt2 to cyclohexenone as test reaction. The best identified ligands were also synthesized separately and investigated in its soluble form. The results obtained for the polymer-bound ligands correctly mirrored the performance of the soluble ligands. The library embodied members giving ee values varying between 3 and 67%. The "positional scanning" approach proved to be invalid for the study of the ligand system, indicating that this approach in general should be applied with care. Taken together, the method allowed for rapid and efficient optimization of the ligands and led to the development of the first enantioselective, Cu-catalyzed conjugate addition reaction with a polymer-bound ligand.