5352-72-7Relevant articles and documents
Asymmetric Conjugate Addition of Chiral Secondary Borylalkyl Copper Species
Jang, Won Jun,Woo, Jeongkyu,Yun, Jaesook
supporting information, p. 4614 - 4618 (2021/01/18)
We report the diastereo- and enantioselective conjugate addition of chiral secondary borylalkyl copper species derived from borylalkenes in situ to α,β-unsaturated diesters. In the presence of a chiral bisphosphine-ligated CuH catalyst, the conjugate addition provides a direct access to enantioenriched alkylboron compounds containing two contiguous carbon stereogenic centers in good yield with high diastereo- and enantioselectivity (up to >98:2 dr, >99:1 er) by assembling readily available starting alkenyl reagents in a single operation without using preformed organometallic reagents or chiral auxiliaries. The resulting products were used in various organic transformations. The utility of the synthetic approach was highlighted by the synthesis of (?)-phaseolinic acid.
Topical ‘dual-soft’ glucocorticoid receptor agonist for dermatology
Carnerup, Martin A.,Dack, Kevin N.,Eirefelt, Stefan,Henriksson, Krister,Johnson, Patrick S.,Ollerstam, Anna K.,Stahlhut, Martin
supporting information, (2020/07/21)
Steroidal glucocorticoids (GR agonists) have been widely used for the topical treatment of skin disorders, including atopic dermatitis. They are a very effective therapy, but they are associated with both unwanted local effects in the skin (skin thinning/atrophy) and systemic side effects. These effects can limit the long-term utility of potent steroids. Here we report on a topically delivered non-steroidal GR agonist, that has the potential to deliver high efficacy in the skin, but due to rapid metabolism in the blood & liver (“dual-soft”) it should have greater systemic safety than existing treatments. In addition, compared to less selective steroidal GR agonists, the new non-steroidal Selective Glucocorticoid Agonists (SEGRAs) have the potential to avoid the skin atrophy observed with existing topical steroids. Due to its potential for reduced skin atrophy and low systemic exposure, LEO 134310 (17) may be suitable for long term topical treatment of skin diseases such as atopic dermatitis and psoriasis.
NON-STEROIDAL GLUCOCORTICOID RECEPTOR MODULATORS FOR LOCAL DRUG DELIVERY
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Page/Page column 57; 58, (2017/04/11)
The present invention relates to a compound according to formula (I) wherein R1 is selected from the group consisting of 5- and 6- membered heteroaryl, (C1- C6)alkyl, (C3-C6)cycloalkyl, (4-6)-membered heterocycloalkyl and phenyl; R2 is selected from (C1-C3)alkyl and halo(C1-C3)alkyl; R3 is selected from phenyl, 5-membered heteroaryl and 6-membered heteroaryl; R4 is selected from hydrogen, halogen, (C1- C4)alkyl and halo(C1-C4)alkyl; X1 is selected from CH, C(Rb) and N, X2 is selected from CH and N; Y is selected from -NH- and -O-; m is 0 or 1; n is 0 or 1; L represents a bond, -O-, -NH- or -N(RC)-; or pharmaceutically acceptable salts, hydrates, or solvates thereof. The invention relates further to intermediates for the preparation of said compounds, to said compounds for use in therapy, to pharmaceutical compositions comprising said compounds, to methods of treating diseases with said compounds, and to the use of said compounds in the manufacture of medicaments.
Stereoselective formation of a functionalized dipeptide isostere by zinc carbenoid-mediated chain extension
Lin, Weimin,Theberge, Cory R.,Henderson, Timothy J.,Zercher, Charles K.,Jasinski, Jerry,Butcher, Ray J.
supporting information; experimental part, p. 645 - 651 (2009/07/04)
The application of a zinc carbenoid-mediated chain-extension reaction to a functionalized peptide isostere is reported. The cleavage site of human CVM protease was utilized as a target for testing the synthetic methodology. The utility of this chain-exten
Formation of γ-lactones through CAN-mediated oxidative cleavage of hemiketals
Jacobine, Alexander M.,Lin, Weimin,Walls, Bethany,Zercher, Charles K.
supporting information; experimental part, p. 7409 - 7412 (2009/05/07)
(Chemical Equation Presented) The generation of substituted γ-lactones can be accomplished through application of a tandem chain extension-aldol reaction, followed by CAN-mediated oxidative cleavage of the aldol product. The oxidative cleavage requires the intermediacy of a hemiketal and the presence of an α-heteroatom. Formation of the γ-lactone through the oxidative cleavage is used to assign stereochemistry of the aldol reaction and as the final step in a short synthesis of members of the phaseolinic acid family of natural products.
Chemoenzymatic synthesis of enantioenriched 5-oxo-tetrahydro-3- furancarboxylic acid derivatives
Comini, Andrea,Forzato, Cristina,Nitti, Patrizia,Pitacco, Giuliana,Valentin, Ennio
, p. 617 - 625 (2007/10/03)
(R)-(+)-Paraconic acid 4, (S)-(-)-terebic acid 6 and their corresponding methyl and ethyl esters having ee's ranging from 60% to 92% were obtained by enzymatic resolution of their racemates. The enzymatic resolution of racemic ethyl γ-methylparaconates 14a and 14b allowed the isolation of the unreacted ester (2R,3R)-(+)-14a and that of the lactonic acid (2S,3R)-(-)-5b with 80% and 93% ee, respectively, the former by the use of Horse liver acetone powder (HLAP), the latter using α-chymotrypsin (α-CT). The enantiomeric ethyl (2S,3S)-(-)-14a and (2S,3R)-(-)-14b, both with >99% ee, were obtained by baker's yeast reduction of diethyl acetylsuccinate.
Preparative Bioorganic Chemistry, XI. - Preparation of the Enantiomers of Paraconic Acid Employing Lipase-Mediated Asymmetric Hydrolysis of Prochiral Diacetates as the Key Step
Mori, Kenji,Chiba, Naoki
, p. 957 - 962 (2007/10/02)
(S)-(-)-Paraconic acid (1) was prepared from 2-(acetoxymethyl)-3-phenylpropyl acetate (4) by its asymmetric hydrolysis with pig pancreatic lipase as the key step.Similarly, (R)-(+)-1 was prepared from 2-(acetoxymethyl)-4-pentenyl acetate (2) by its asymme
SYNTHESIS OF OPTICALLY ACTIVE FORMS OF A-FACTOR, THE INDUCER OF STREPTOMYCIN BIOSYNTHESIS IN INACTIVE MUTANTS OF STREPTOMYCES GRISEUS
Mori, Kenji,Yamane, Kazusuke
, p. 2919 - 2921 (2007/10/02)
The absolute configuration at C-3 of A-factor, 2-(6-methylheptanoyl)-3-hydroxymethyl-4-butanolide 1a, was determined to be S by synthesizing both enantiomers of it from paraconic acid. (3S)-A-factor was 2.5 times more active than the (3R)-isomer as the inducer of streptomycin biosynthesis in inactive mutants of Streptomyces griseus.
