Asymmetric Dihydroxylation Reaction Research Articles

Synthesis and preliminary antifungal evaluation of a library of phytosphingolipid analogues

A library of 64 phytosphingolipid analogues resulting from the systematic variation of the C1, C3, C4, and the N-acyl moiety of phytosphingosine (PHS) has been prepared from common scaffolds derived from the chiral pool and Sharpless asymmetric dihydroxylation reactions. Library members have been evaluated as growth inhibitors of the yeast Saccaromyces cerevisiae. In addition, 1-amino-N-pivaloyl PHS analogues were also tested as IPC synthase inhibitors, in comparison with the natural product khafrefungin.

A Short and Efficient Enantiomeric Synthesis of Antitumor Fused Tetrahydrofurans

AbstractA short and efficient enantiomeric synthesis of fused tetrahydrofuran derivatives is reported. The methodology is based on a regio‐ and stereoselective double exo‐cyclization of enantiomeric bis‐epoxy‐diols. The six stereocenters of the bis‐epoxy diols were introduced by the application of Katsuki–Sharpless asymmetric epoxidation and Sharpless asymmetric dihydroxylation reactions. In vitro cytotoxicities on HL60 human promyelocytic leukemia cells were determined for the bicyclic products. Active products showed exceptionally steep dose–response curves and DNA laddering. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Preferential formation of (5S,6R)-thymine glycol for oligodeoxyribonucleotide synthesis and analysis of drug binding to thymine glycol-containing DNA

We previously reported the chemical synthesis of oligonucleotides containing thymine glycol, a major form of oxidative DNA damage. In the preparation of the phosphoramidite building block, the predominant product of the osmium tetroxide oxidation of protected thymidine was (5R,6S)-thymidine glycol. To obtain the building block of the other isomer, (5S,6R)-thymidine glycol, in an amount sufficient for oligonucleotide synthesis, the Sharpless asymmetric dihydroxylation (AD) reaction was examined. Although the reaction was very slow, (5S,6R)-thymidine glycol was obtained in preference to the (5R,6S) isomer. The ratio of (5S,6R)- and (5R,6S)-thymidine glycols was 2:1, and a trans isomer was also formed. When an ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate, was used as a co-solvent, the reaction became faster, and the yield was improved without changing the preference. The phosphoramidite building block of (5S,6R)-thymidine glycol was prepared, and oligonucleotides containing 5S-thymine glycol were synthesized. One of the oligonucleotides was used to analyze the binding of distamycin A to thymine glycol-containing DNA by Circular dichroism (CD) spectroscopy and surface plasmon resonance (SPR) measurements. Distamycin A bound to a duplex containing either isomer of thymine glycol within the AATT target site, and its binding was observed even when the thymine glycol was placed opposite cytosine.

Markedly Enhanced Recyclability of Osmium Catalyst in Asymmetric Dihydroxylation Reactions by Using Macroporous Resins Bearing Both Residual Vinyl Groups and Quaternary Ammonium Moieties.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly stereoselective synthesis of antitumor agents: both enantiomers of goniothales diol, altholactone, and isoaltholactone

A flexible stereoselective route to synthesize both enantiomers of the highly functionalized substituted tetrahydrofurans and α,β-unsaturated-δ-lactones, goniothales diol, altholactone, and isoaltholactone, from readily available cinnamyl alcohol is described. This approach derived its asymmetry from Sharpless catalytic asymmetric epoxidation and Sharpless asymmetric dihydroxylation reactions. The resulting diols were produced in high enantiomeric excess and were cyclized in a stereoselective manner in the presence of a catalytic amount of camphor sulfonic acid.

A Bidirectional Approach to the Synthesis of a Complete Library of Adjacent-Bis-THF Annonaceous Acetogenins

Thirty-six stereoisomers of bifunctional adjacent bis-THF (tetrahydrofuran) lactones have been synthesized, which can afford a complete library of the adjacent bis-THF Annonaceous acetogenins. The bis-THF lactones were synthesized, starting from the enantioselectively pure 8,9:12,13-(E,E and Z,E)-16-benzyloxy-5-hydroxy-hexadeca-1,4-olide, in a highly distereoselective manner using oxidative reactions, including rhenium(VII) oxides-mediated oxidative cyclization, Shi's asymmetric epoxidation, and Sharpless asymmetric dihydroxylation reactions. Using the nonsymmetrical bis-THF lactones, syntheses of two nonnatural acetogenins were achieved.

A Convenient Enantioselective Synthesis of (S)-α-Trifluoromethylisoserine

[reaction: see text] This report describes two straightforward synthetic methodologies to obtain alpha-CF3-isoserine, a new alpha,alpha-disubstituted beta-amino acid, from alpha-(trifluoromethyl)acrylic acid. The routes involve the synthesis of five-membered cyclic sulfates (using sulfuryl chloride) or sulfamidates (using the Burgess reagent) from the corresponding chiral diols, which are obtained by a catalytic asymmetric dihydroxylation (AD) reaction.

Polysiloxane‐Bound Ligand Accelerated Catalysis: A Modular Approach to Heterogeneous and Homogeneous Macromolecular Asymmetric Dihydroxylation Ligands.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Markedly enhanced recyclability of osmium catalyst in asymmetric dihydroxylation reactions by using macroporous resins bearing both residual vinyl groups and quaternary ammonium moieties

Markedly enhanced recyclability of osmium catalyst in asymmetric dihydroxylation has been achieved by using osmylated macroporous resins bearing both residual vinyl groups and quaternary ammonium moiety.

A Stereodivergent Asymmetric Approach to Difluorinated Aldonic Acids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of a New Chiral Nonracemic C2‐Symmetric 2,2′‐Bipyridyl Ligand and Its Application in Copper(I)‐Catalyzed Enantioselective Cyclopropanation Reactions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Development of protocols for the separation of Os catalysts from organic products in the catalytic dihydroxylation of olefins

Abstract Different approaches were investigated to achieve separation of osmium species from products in the course of the asymmetric dihydroxylation (AD) reaction. Prerequisite for these examinations was the development of a routine method for the detection of electrophilic osmium species in organic product solutions. For recycling of the catalyst an osmium alkaloid complex was immobilised by introducing an ionic group into the ligand and embedding the catalyst in a polyelectrolyte matrix. In addition, the native polymeric aminosugar chitin was used as ligand as well as a support in the dihydroxylation for the first time. These chitin-based catalysts showed good productivities and retention of osmium from the products was ensured using NMO as the oxidant. However, the catalytic reaction did not proceed enantioselectively. Enantiomerically enriched diols were obtained in high yields without significant contamination of osmium applying a homogeneous AD with bleach as the oxidant with a downstream separation of the 1,2-diol from the catalyst by extraction. The remaining osmium-containing solution has been recycled up to eight times without loss of activity and enantioselectivity.

Total synthesis of 34-hydroxyasimicin and its photoactive derivative for affinity labeling of the mitochondrial complex I.

The asymmetric total synthesis of the 34-hydroxyasimicin and its 3-(4-benzoylphenyl)propionate ester was achieved by means of a convergent synthetic strategy. This ester, which contains eight asymmetric centers, represents the first photoaffinity-labeling agent that is derived from an Annonaceous acetogenin. The key transformations in the synthesis include the Sharpless asymmetric dihydroxylation reaction, the Wittig olefination reaction, an oxidative cyclization reaction with rhenium(vii) oxide, the Williamson etherification reaction, and a palladium-catalyzed cross-coupling reaction. Use of the target molecule for photoaffinity-labeling studies of bovine mitochondrial NADH-ubiquinone oxidoreductase (Complex I) may shed light on the structure/function of this intricate enzyme and on the origin of the high antitumor activity exhibited by the Annonaceous acetogenins.

Synthesis of a new chiral nonracemic C(2)-symmetric 2,2'-bipyridyl ligand and its application in copper(I)-catalyzed enantioselective cyclopropanation reactions.

An efficient synthesis of a low molecular weight, chiral nonracemic and C(2)-symmetric bipyridyl ligand is reported. The ligand was prepared using a catalytic asymmetric dihydroxylation reaction of a pyrindine as a key step. The ligand was evaluated in the asymmetric copper(I)-catalyzed cyclopropanation reactions of a series of alkenes and diazoesters. Very high diastereoselectivities and enantioselectivities were observed (>95:5 dr and up to 99% ee). These are the highest reported stereoselectivities for a chiral bipyridyl ligand. [structure: see text]

Asymmetric Synthesis of Cyclic Hydroxy Ketones Derived from Enol Ethers via Sharpless Asymmetric Dihydroxylation. A Study in the Correlation of the Enol Ether Chain Length and Enantioselectivity.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Polysiloxane-bound ligand accelerated catalysis: a modular approach to heterogeneous and homogeneous macromolecular asymmetric dihydroxylation ligands.

Polysiloxane acts as a modular scaffold for macromolecular reagent development. Two separate components were covalently integrated into one material, one constituent provided reagent functionality, the other modulated solubility. In particular cinchona alkaloid based ligands used in the osmium tetroxide catalyzed asymmetric dihydroxylation (AD) reaction were covalently attached to commercially available polysiloxane. To enhance the reactivity of these polymeric ligands, multifunctional reagents were designed to include both the cinchona alkaloid and an alkoxyethylester solubilizing moiety providing random co-polymers. While the mono-functional materials led to heterogeneous conditions, the bi-functional polymers resulted in homogeneous reaction mixtures. Although both reagent types provided diol products with excellent yield and selectivity (>99% ee in nearly quantitative yield) the homogeneous analog has nearly twice the reactivity. Every repeat unit in the heterogeneous material was functionalized along the polysiloxane backbone while approximately half of these sites contained ligand in the homogeneous version. This approach led to macromolecular catalysts with high loadings of ligand and therefore materials with very low equivalent weights. Although these polymers are highly loaded they do maintain reactivity on a par with their free ligand counterpart. Using straightforward purification techniques (i.e. precipitation, simple filtration, or ultrafiltration) these polymeric ligands were easily separated from diol product and reused multiple times. Polysiloxane is a viable support for the catalysis of AD reactions and may provide a generally useful backbone for other catalytic systems.

Studies on the Asymmetric Dihydroxylation of Advanced Bryostatin C-Ring Segments

The asymmetric dihydroxylation reaction of early stage and advanced Bryostatin C-ring precursors was evaluated. For homoallylic ethers and alcohols, several AD ligands were investigated including a novel class of quinidine-alkynes.

A stereodivergent asymmetric approach to difluorinated aldonic acids.

A (bromodifluoromethyl)alkyne has been deployed in a stereoselective route to difluorinated aldonic acid analogues, in which a Sharpless asymmetric dihydroxylation reaction and diastereoisomer separation set the stage for phenyl group oxidation.

Enantioselective Total Synthesis of Chiricanine B.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric synthesis of cyclic hydroxy ketones derived from enol ethers via sharpless asymmetric dihydroxylation. A study in the correlation of the enol ether chain length and enantioselectivity.

The Sharpless asymmetric dihydroxylation reaction of enol ethers derived from their corresponding cyclic ketones, gave alpha-hydroxyketones with high enantioselectivity. The enantiomeric excess was found to be proportional to the length of the unbranched enol ether chain with a maximum ee for the pentyl enol ether. An efficient synthesis of alpha-hydroxy chromanone in >90% ee was demonstrated using this method.