Efficient Desymmetrization of “Pseudo”-C2-Symmetric Substrates:  Illustration in the Synthesis of a Disubstituted Butenolide from Arabitol

Linclau, Bruno; Boydell, A. James; Clarke, Phillip J.; Horan, Richard A. J.; Jacquet, Claire

doi:10.1021/jo026696r

Cited by 16 publications

(11 citation statements)

References 42 publications

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“…Briefly, 2,4-dihydroxypentane-1,5-diyl bis-(2,4,6triisopropyl-1-benzenesulfonate) 6a was obtained in 5 steps starting from L-(−)-arabitol. 38 Acetonization of bis-sulfonate 6a followed by iodination and deacetionization provided diiodo diol 9a which was treated directly with an excess of 2,6dihydroxyacetophenone to give the substitution adduct 10a. A two-step cyclization sequence from modified conditions 39 built the chromonyl ring of diester 11a.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Stereochemical Control of Nonamphiphilic Lyotropic Liquid Crystals: Chiral Nematic Phase of Assemblies Separated by Six Nanometers of Aqueous Solvents

et al. 2013

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Unlike conventional thermotropic and lyotropic liquid crystals, nonamphiphilic lyotropic liquid crystals consist of hydrated assemblies of nonamphiphilic molecules that are aligned with a separation of about 6 nm between assemblies in an aqueous environment. This separation raises the question of how chirality, either from chiral mesogens or chiral dopants, would impact the phase as the assemblies that need to interact with each other are about 6 nm apart. Here, we report the synthesis of three stereoisomers of disodium chromonyl carboxylate, 5′DSCG-diviol, and the correlation between the molecular structure, bulk assembly, and liquid crystal formation. We observed that the chiral isomers (enantiomers 5′DSCG-(R,R)-diviol and 5′DSCG-(S,S)-diviol) formed liquid crystals while the achiral isomer 5′DSCG-meso-diviol did not. Circular dichroism indicated a chiral conformation with bisignate cotton effect. The nuclear Overhauser effect in proton NMR spectroscopy revealed conformations that are responsible for liquid crystal formation. Cryogenic transmission electron microscopy showed that chiral 5′DSCG-diviols form assemblies with crossings. Interestingly, only planar alignment of the chiral nematic phase was observed in liquid crystal cells with thin spacers. The homeotropic alignment that permitted a fingerprint texture was obtained only when the thickness of the liquid crystal cell was increase to above ∼500 μm. These studies suggest that hydrated assemblies of chiral 5′DSCG-diviol can interact with each other across a 6 nm separation in an aqueous environment by having a twist angle of about 0.22°throughout the sample between the neighboring assemblies.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Stereochemical Control of Nonamphiphilic Lyotropic Liquid Crystals: Chiral Nematic Phase of Assemblies Separated by Six Nanometers of Aqueous Solvents

et al. 2013

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“…The average yields were 75% to 82%. 41,42 . To a stirring solution of (+)-diethyl-L-tartrate (5.2 g, 25.22 mmol) in toluene (50 mL) p-toluenesulfonic acid (480 mg, 2.52 mmol) and cyclopentanone (5.03 mL, 63.05 mmol) were added respectively.…”

Section: General Methodsmentioning

confidence: 99%

“…Mp: 77-78 1C [ref. 1 75.3-76.6 1C]; 31-7.22 (m, 5H), 5.17 (br s, 3H), 4.51 (dd, J = 11.6, J = 11.6 Hz, 2H), 3.85-3.38 (m, 6H); 13 C NMR (100 MHz, CDCl 3 ): d ppm 137.9, 128.7, 128.2, 79.3, 72.7, 72.1, 63.4, 60.7;FT-IR (KBr) n 3403, 2938, 1638, 1454, 1213, 1050 (2S,3S)-2,4-bis(benzyloxy)butane-1,3-diol ( 15) and (S)-4-((S)-1,2bis(benzyloxy)ethyl)-2,2-dimethyl-1,3-dioxolane (16) 41,43,47,48 . Silver oxide (Ag 2 O, 1.479 g, 4.597 mmol) and benzyl bromide (400.5 ml, 3.371 mmol) were added to a solution of (2S,3S)-3-(benzyloxy) -1,2,4-triol (13, 650 mg, 3.065 mmol) in anhydrous dichloromethane under a N 2 atmosphere and the stirring was continued for 8 h. After completion of the reaction (monitored by TLC), the reaction mixture was filtered off through a pad of Celite.…”

Section: General Methodsmentioning

confidence: 99%

“…Lipids 1a and 1b were prepared in six steps from (+)-diethyl L-tartrate as shown in Scheme 1. Introduction of cyclopentylidene acetal 41,42 into diol of (+)-diethyl L-tartrate (5) and subsequent ester reduction of fully protected tartrate analog 6 by 2.2 equiv. of lithium aluminium hydride 43 resulted in bishydroxymethyl compound 7 in 78% yield (two steps).…”

Section: Synthesismentioning

confidence: 99%

“…of silver oxide in anhydrous dichloromethane 47 resulted in a non-separable mixture of 1,2-diol ( 14) and 1,3-diol (15) as major products. Regioselective protection of the mixture of and 15 via acetonide formation 41,43,48 provided fully protected 16 in 44% yield (two steps) and unprotected 15 in 43% yield (two steps). The acyl chains were installed into 15 using the standard DCC-mediated coupling reaction 45 with palmitic acid to yield 17a and octanoic acid to yield 17b.…”

Section: Synthesismentioning

confidence: 99%

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Development of diacyltetrol lipids as activators for the C1 domain of protein kinase C

et al. 2012

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The protein kinase C (PKC) family of serine/threonine kinases is an attractive drug target for the treatment of cancer and other diseases. Diacylglycerol (DAG), phorbol esters and others act as ligands for the C1 domain of PKC isoforms. Inspection of the crystal structure of the PKCδ C1b subdomain in complex with phorbol-13-O-acetate shows that one carbonyl group and two hydroxyl groups play pivotal roles in recognition of the C1 domain. To understand the importance of two hydroxyl groups of phorbol esters in PKC binding and to develop effective PKC activators, we synthesized DAG like diacyltetrols (DATs) and studied binding affinities with C1b subdomains of PKCδ and PKCθ. DATs, with the stereochemistry of natural DAGs at the sn-2 position, were synthesized from (+)-diethyl L-tartrate in four to seven steps as single isomers. The calculated EC(50) values for the short and long chain DATs varied in the range of 3-6 μM. Furthermore, the fluorescence anisotropy values of the proteins were increased in the presence of DATs in a similar manner to that of DAGs. Molecular docking of DATs (1b-4b) with PKCδ C1b showed that the DATs form hydrogen bonds with the polar residues and backbone of the protein, at the same binding site, as that of DAG and phorbol esters. Our findings reveal that DATs represent an attractive group of C1 domain ligands that can be used as research tools or further structurally modified for potential drug development.

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Trost Desymmetrization

2010

Comprehensive Organic Name Reactions and Reagents

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Desymmetrization means to remove a symmetric element from the substrate and it may take place in the presence of an enzyme or a nonenzymatic catalyst. Among the known nonenzymatic desymmetrization processes, the most common one is the palladium‐catalyzed desymmetrization of meso ‐2‐ene‐1,4‐diols. Overall, the desymmetrization of meso ‐compounds is getting popular because it can offer asymmetric synthons of high value via a limited number of steps. Many desymmtrization protocols have been summarized. This type of transformation has wide application in organic synthesis.

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Efficient Desymmetrization of “Pseudo”-C₂-Symmetric Substrates: Illustration in the Synthesis of a Disubstituted Butenolide from Arabitol

Cited by 16 publications

References 42 publications

Stereochemical Control of Nonamphiphilic Lyotropic Liquid Crystals: Chiral Nematic Phase of Assemblies Separated by Six Nanometers of Aqueous Solvents

Stereochemical Control of Nonamphiphilic Lyotropic Liquid Crystals: Chiral Nematic Phase of Assemblies Separated by Six Nanometers of Aqueous Solvents

Development of diacyltetrol lipids as activators for the C1 domain of protein kinase C

Trost Desymmetrization

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