90107-01-0Relevant articles and documents
Umpolung Strategy for Arene C?H Etherification Leading to Functionalized Chromanes Enabled by I(III) N-Ligated Hypervalent Iodine Reagents
Mikhael, Myriam,Guo, Wentao,Tantillo, Dean J.,Wengryniuk, Sarah E.
, p. 4867 - 4875 (2021/09/14)
The direct formation of aryl C?O bonds via the intramolecular dehydrogenative coupling of a C?H bond and a pendant alcohol represents a powerful synthetic transformation. Herein, we report a method for intramolecular arene C?H etherification via an umpoled alcohol cyclization mediated by an I(III) N-HVI reagent. This approach provides access to functionalized chromane scaffolds from primary, secondary and tertiary alcohols via a cascade cyclization-iodonium salt formation, the latter providing a versatile functional handle for downstream derivatization. Computational studies support initial formation of an umpoled O-intermediate via I(III) ligand exchange, followed by competitive direct and spirocyclization/1,2-shift pathways. (Figure presented.).
Optically active N- and C-terminal building blocks for the synthesis of peptidyl olefin peptidomimetics
Mirilashvili, Sima,Chasid-Rubinstein, Naama,Albeck, Amnon
experimental part, p. 4671 - 4686 (2010/10/19)
Peptidyl olefin peptidomimetics serve as biologically active compounds or as intermediates for other peptidyl isosteres. The N-terminal side of the C=C bond could be easily prepared in an optically pure form from α-amino acids. Synthesis of C-terminal building blocks in an optically pure form is more challenging. We developed a chemoenzymatic stereoselective approach to such optically active C-terminal building blocks to be assembled into peptidyl olefins by a variety of reactions. They include an electrophilic aldehyde and nucleophilic sulfone, phosphonium salt, phosphonate, and diselenide. Key enzymatic hydrolysis of prochiral diesters to the corresponding hydroxy esters introduces optical activity. The sequence of the subsequent chemical reactions, either protection- hydrolysis-functionalization or functionalization-hydrolysis- protection, determines the absolute stereochemistry of the final building blocks.
Optically active γ-hydroxy sulfone Julia reagents for the synthesis of peptidyl olefin peptidomimetics
Mirilashvili, Sima,Chasid-Rubinstein, Naama,Albeck, Amnon
supporting information; experimental part, p. 3461 - 3464 (2009/04/14)
Peptidyl olefin peptidomimetics serve as biologically active compounds or as intermediates for other peptidyl isosteres. We developed a chemoenzymatic stereoselective approach to optically active γ-hydroxy sulfones to be assembled into peptidyl olefins by the Julia reaction. Key enzymatic hydrolysis of prochiral diesters to the corresponding hydroxy esters introduces optical activity. The sequence of the subsequent chemical reactions, either protection-hydrolysis-functionalization or functionalization-hydrolysis- protection, determines the absolute stereochemistry of the final sulfone building block. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
Chemoenzymatic synthesis of enantiomerically enriched α-chiral 3-oxy-propionaldehydes by lipase-catalyzed kinetic resolution and desymmetrization
Wiktelius, Daniel,Larsson, Emma K.,Luthman, Kristina
, p. 2088 - 2100 (2007/10/03)
Enantiomerically enriched phenylalanine- and leucine aldehyde analogues have been prepared by lipase catalyzed desymmetrization or kinetic resolution of 1,3-propanediol derivatives as key steps. Observations of unusual enantioselectivity were made, and mo
Vanilloid analogues containing resinferatoxin pharmacophores as potent vanilloid receptor agonists and analgesics, compositions and uses thereof
-
, (2008/06/13)
The present invention is related to new vanilloid analogues containing resiniferatoxin pharmacophores, pharmaceutical compositions comprising such analogues, and their uses as vanilloid receptor agonists and potent analgesics. The present invention provides a pharmaceutical composition for treating acute, chronic, inflammatory or neuropathic pains or for treating bladder hypersensitivity.
N-(3-acyloxy-2-benzylpropyl)-N′-(4-hydroxy-3-methoxybenzyl)thiourea derivatives as potent vanilloid receptor agonists and analgesics
Lee, Jeewoo,Lee, Jiyoun,Kim, Jiyoung,Kim, Soo Yeon,Chun, Moon Woo,Cho, Hawon,Hwang, Sun Wook,Oh, Uhtaek,Park, Young Ho,Marquez, Victor E.,Beheshti, Maryam,Szabo, Tamas,Blumberg, Peter M.
, p. 19 - 32 (2007/10/03)
A series of N-(3-acyloxy-2-benzylpropyl)-N′-(4-hydroxy-3-methoxybenzyl)thiourea derivatives were investigated as vanilloid receptor ligands in an effort to discover a novel class of analgesics. The proposed pharmacophore model of resiniferatoxin, which includes the C20-homovanillic moiety, the C3-carbonyl and the orthoester phenyl ring as key pharmacophoric groups, was utilized as a guide for drug design. The compounds were synthesized after several steps from diethylmalonate and evaluated in vitro in a receptor binding assay and in a capsaicin-activated channel assay. Additional evaluation of analgesic activity, anti-inflammatory activity and pungency was conducted in animal models by the writhing test, the ear edema assay, and the eye-wiping test, respectively. Among the new compounds, 23 and 28 were found to be the most potent receptor agonists of the series with Ki values of 19 nM and 11 nM, respectively. Their strong in vitro potencies were also reflected by an excellent analgesic profile in animal tests with ED50 values of 0.5 μg/kg for 23 and 1.0 μg/kg for 28. Relative to capsaicin these compounds appear to be ca. 600 and 300 times more potent. Both 23 and 28 were found to be less pungent than capsaicin based on the eye-wiping test. However, the compounds did not show significant anti-inflammatory activity. A molecular modeling study comparing the energy-minimized structures of resiniferatoxin and 35 demonstrated a good correlation in the spatial disposition of the corresponding key pharmacophores. The thioureas described in this investigation, which were designed as simplified resiniferatoxin surrogates, represent a novel class of potent vanilloid receptor agonists endowed with potent analgesic activity and reduced pungency.
3-Acyloxy-2-phenalkylpropyl amides and esters of homovanillic acid as novel vanilloid receptor agonists
Lee, Jeewoo,Park, Shin-Ung,Kim, Ji-Young,Kim, Jin-Kwan,Lee, Jiyoun,Oh, Uhtaek,Marquez, Victor E.,Beheshti, Maryam,Wang, Qiming J.,Modarres, Shayan,Blumberg, Peter M.
, p. 2909 - 2914 (2007/10/03)
A series of 3-acyloxy-2-phenalkylpropyl amides and esters of homovanillic acid were designed and synthesized as vanilloid receptor agonists containing the three principal pharmacophores of resiniferatoxin. Amide analogues 23, 5 and 11 were found to be potent agonists in vanilloid receptor assay both for ligand binding and for activation.
Prediction of the solvent dependence of enzymatic prochiral selectivity by means of structure-based thermodynamic calculations
Ke,Wescott,Klibanov
, p. 3366 - 3374 (2007/10/03)
A new, quantitative model is elaborated to rationalize the solvent dependence of enzymatic selectivity solely on the basis of the thermodynamics of substrate solvation. The model predicts that any type of the selectivity (defined as the ratio of k(cat)/K(
Silylmethyl Radical Cyclization: New Stereoselective Method for 1,3-Diol Synthesis from Allylic Alcohols
Nishiyama, Hisao,Kitajima, Toshio,Matsumoto, Makoto,Itoh, Kenji
, p. 2298 - 2300 (2007/10/02)
Cyclizations of (bromomethyl)dimethylsilyl allylic ethers by treatment with tri-n-butyltin hydride in a free-radical process followed by oxidation in a one-pot manner with hydrogen peroxide gave th corresponding 1,3-diols predominantly with high stereoselectivity.
