- Biology-oriented synthesis of a withanolide-inspired compound collection reveals novel modulators of hedgehog signaling
-
Biology-oriented synthesis employs the structural information encoded in complex natural products to guide the synthesis of compound collections enriched in bioactivity. The trans-hydrindane dehydro-δ-lactone motif defines the characteristic scaffold of the steroid-like withanolides, a plant-derived natural product class with a diverse pattern of bioactivity. A withanolide-inspired compound collection was synthesized by making use of three key intermediates that contain this characteristic framework derivatized with different reactive functional groups. Biological evaluation of the compound collection in cell-based assays that monitored biological signal-transduction processes revealed a novel class of Hedgehog signaling inhibitors that target the protein Smoothened. BIOS delivers a collection of compounds with the trans-hydrindane dehydro-δ-lactone scaffold, which are based on the withanolide natural products, in a stereoselective fashion. A biological investigation of the compounds revealed novel and potent inhibitors of the Hedgehog signaling pathway, which bind to the protein Smoothened.
- venda, Jakub,Sheremet, Michael,Kremer, Lea,Maier, Luk,Ziegler, Slava,Kumar, Kamal,Waldmann, Herbert,Bauer, Jonathan O.,Strohmann, Carsten
-
supporting information
p. 5596 - 5602
(2015/06/01)
-
- Synthesis and ultraviolet absorption characteristics of 4-arylidene isopinocamphones from α-pinene
-
A new series of 4-arylidene isopinocamphones were synthesized from α-pinene which is a natural chemical from pine tree and their ultraviolet absorption characteristics were investigated. (+)Isopinocamphone was obtained from α-pinene by hydroboration-oxidation and then it was reacted with benzaldehyde, p-methylbenzaldehyde, p -methoxybenzaldehyde, p-chlorobenzaldehyde, furfural and p -nitrobenzaldehyde in the presence of alkali catalysts to get 4-arylidene isopinocamphones including 2-benzylidene-4,6,6-trimethylbicyclo[3.1.1]heptan-3-one (1), 2,6,6-trimethyl-4-(4-methyl benzyl)bicyclo[3.1.1]heptane-3-one (2), 2-(4-methoxybenzylidene)-4,6,6-trimethylbicyclo[3.1.1] heptan-3-one ( 3 ), 2-(4-chlorobenzylidene)-4,6,6-trimethylbicyclo[3.1.1]heptan-3-one (4 ), 2-(furan-2-methylene)-4,6,6-trimethylbicyclic [3.1.1] heptane-3-one (5) and 2,6,6-trimethyl-4-(4-nitrobenzylidene)bicyclo[3.1.1]heptan-3-one (6). he structures of 4-arylidene isopinocamphones were determined by FT-IR, 1H NMR, 13/C NMR and GC-MS technique. Their ultraviolet absorption characteristics and light stability was further examined. The results showed that compounds 1 , 2, 3 and 5 could be used as Btype UV absorbents, compounds 4 and 6 could be used as A-type UV absorbents and compounds 6 had both functions as UV-A and UVB types absorbents. The light stability sequence of these compounds was (2 ) > (1) ≈ (3) ≈ (4) ≈(6) > (5).
- Wang, Jia-Y.U.,Wang, Peng-N.A.,Yang, Jin-Lai,Shen, Jia,Xu,Wang, Shi-F. A.
-
p. 7779 - 7784
(2015/02/02)
-
- Use of immobilized transition metal complexes as recyclable catalysts for oxidation reactions with hydrogen peroxide as oxidant
-
A tetradentate Schiff base (teta), obtained from triethylenetetramine and salicylaldehyde, has been covalently bonded to divinylbenzene cross-linked chloromethylated polystyrene. This chelating ligand, abbreviated as PS-teta (PS = polymeric support), reacts with metal chlorides (Cu2+, Co 2+, and Ni2+) in methanol to give polymerbound transition metal complexes, PS-Cu(II)teta/(Cat-1), PS-Ni(II)teta/(Cat-2), and PS-Co(II)teta/(Cat-3), formation of which has been established by various physiochemical methods and spectroscopic techniques. The catalytic potential of these materials has been tested for the oxidation of various alkenes, alkanes, alcohols, and thioethers in the presence of 30% H2O2 as an oxidant. At the same time, these catalysts are very stable and could be reused in oxidation reactions for more than five times without noticeable loss of their catalytic activity. Springer Science+Business Media B.V. 2011.
- Islam, Sk Manirul,Mobarok, Manir,Mondal, Paramita,Roy, Anupam Singha,Salam, Noor,Hossain, Dildar,Mondal, Sanchita
-
experimental part
p. 97 - 107
(2012/09/22)
-
- Reductive deprotection of propargyl ether by a SmI2-amine-water system and its application to polymer-supported oligosaccharide synthesis
-
A SmI2-amine-water system instantaneously deprotected aryl and alkyl propargyl ethers in a reductive manner. The utility of the propargyl group as a protecting group in oligosaccharide synthesis, and its application to polymer-supported oligosaccharide synthesis is described.
- Manabe, Shino,Ueki, Akiharu,Ito, Yukishige
-
p. 5159 - 5161
(2008/12/20)
-
- An improved procedure for the separation of (+) or (-)-isopinocampheol, the major side product of the oxidation workup procedure of Brown's asymmetric crotylborations
-
Separation of (+) or (-)-isopinocampheol, the major side product of the oxidation workup procedure of Brown's asymmetric reactions such as crotylborations from the desired product is quite tedious and often requires repeated column chromatography. It is discovered that a sublimation process can be used to easily separate this major side product.
- Hua, Zhengmao,Jin, Zhendong
-
p. 7695 - 7697
(2008/03/30)
-
- Toward the creation of NMR databases in chiral solvents: bidentate chiral NMR solvents for assignment of the absolute configuration of acyclic secondary alcohols.
-
The absolute configuration of acyclic secondary alcohols can be established from analysis of the chemical shift behaviors of the adjacent carbons in bidentate chiral solvents (R,R)- and (S,S)-1d as formulated in the boxed illustration.
- Kobayashi, Yoshihisa,Hayashi, Nobuyuki,Kishi, Yoshito
-
p. 411 - 414
(2007/10/03)
-
- A practical olefin hydroboration under liquid-liquid phase transfer catalysis conditions
-
The hydroboration of a series of representative olefins under LL-PTC conditions, followed by oxidative workup provides the corresponding alcohols in excellent yields and regio- and stereoselectivity.
- Albanese, Domenico,Landini, Dario,Maia, Angelamaria,Penso, Michele
-
p. 997 - 998
(2007/10/03)
-
- The cleavage of meso-epoxides with homochiral thiols: Synthesis of (+)- and (-)-trans-1-mercaptocyclohexan-2-ol
-
The synthesis of (+)- and (-)-trans-1-mercaptocyclohexan-2-ol is described. Ring opening of cyclohexene oxide with (-)-4-methoxybenzylnopan- 3(R)-thiol 1a followed by oxidation gives two readily separable diastereomeric sulfoxides. These sulfoxides display very different thermal stability but both undergo regio-specific syn-elimination to give cyclohexan- 1-ol-2-sulfenic acid that can be reacted in situ with 3,5-dimethylthiophenol to give a mixed disulfide. Reduction of these disulfides with lithium aluminium hydride gives the title compounds in enantiomerically pure form.
- Adams, Harry,Bell, Richard,Cheung, Yiu-Yin,Jones, D. Neville,Tomkinson, Nicholas C.O.
-
p. 4129 - 4142
(2007/10/03)
-
- A simple procedure for hydroboration using tetrabutylammonium borohydride
-
Tetrabutylammonium borohydride hydroborates unsaturated systems in refluxing chloroform. With eneynes, selectivity is observed for terminal unsaturation. However, selectivity is not observed with dienes.
- Narasimhan, S.,Swarnalakshmi, S.,Balakumar, R.
-
p. 1189 - 1190
(2007/10/03)
-
- Part II: Transformations of α and β-Pinene Oxides over Binary Oxide Catalysts of Alumina-Rare Earth Oxides
-
The catalytic activity of binary oxides of Al2O3-Eu2O3, Al2O3-Sm2O3, Al2O3-NdO3, Al2O3-Pr6O11, and Al2O3-Y2O3 were checked in the transformations of α and β-pinene oxides.Al2O3-Eu2O3 and Al2O3-Nd2O3 are found to be best catalysts for α-pinene oxide isomeriztion.Among the oxiranes, α-pinene oxide showed more activity mainly yielding 2,2,3-trimethyl cyclopentene-1-acetaldehyde. β-pinene oxide produced trans-myrtanal and myrtanol.
- Jayasree, Janakiamma,Narayanan, Cadavallore S.
-
-
- Samarium(III)-Catalyzed Hydroboration of Olefins with Catecholborane. AGeneral Approach to the Synthesis of Boronate Esters
-
A broad selection of olefins undergo hydroboration with catecholborane in a reaction that is catalyzed by a range of samarium(III) as well as other lanthanide complexes.
- Evans, David A.,Muci, Alexander R.,Stuermer, Rainer
-
p. 5307 - 5309
(2007/10/02)
-
- Chiral synthesis via organoboranes. XVI. Boroxazolidones derived from α-amino acids and borinic or boronic esters. A simple procedure for upgrading borinates and boronates to materials of high optical purity
-
The synthesis of boron heterocycles from borinic and boronic esters with α-amino acids was explored as a means of upgrading the optical purities of intermediates from asymmetric hydroboration.B-Methoxy-9-borabicyclononane, methyl dicyclohexylborinate and (+)- and (-)-methyl diisopinocampheylborinate react with various α-amino acids to form the corresponding crystalline chelates.Recrystallization of the chelates derived from methyl trans-2-phenylcyclopentylisopinocampheylborinate of 85percent ee with l-phenylalanine, methyl isopinocampheyl-exo-norbornylborinate of 83percent ee with l-proline and both optical isomers of methyl diisopinocampheylborinate of 92percent ee with l-proline yield the corresponding products with optical purities approaching 100percent ee.Dimethyl cyclopentylboronate, dimethyl exo-norbornylboronate and dimethyl isopinocampheylboronate upon treatment with iminodiacetic acid and N-methyliminodiacetic acid form the corresponding bicyclic boronates.Recrystallization of the chelate derived from diethyl 3-tetrahydropyranylboronate and iminodiacetic acid yields a product of essentially 100percent ee.Consequently formation of boroxazolidones of asymmetric hydroboration products provides one possible route to upgrade such products to materials of high optical purity.
- Brown, Herbert C.,Gupta, Ashok K.
-
-
- Oxidoreduction between Cycloalkanols and the Corresponding Cycloalkanones in the Cultured Cells of Nicotiana tabacum. Simulation of the Time Courses in the Oxidoreduction
-
A method for the simulation of the time courses in the oxidation of cycloalkanols and the reduction of cycloalkanones in the cultured cells of Nicotiana tabacum was developed on the basis of the permeability of these compounds into the cultured cells and the 13C NMR chemical shift of the carbonyl carbon of the cycloalkanones.Further, the method has been applied to the simulation of the time courses in the oxidation of (+)-borneol and (+)-isopinocampheol and the reduction of (-)-carvomenthone in the cultured cells of N. tabacum.
- Izumi, Shunsuke,Suga, Takayuki
-
p. 1715 - 1720
(2007/10/02)
-
- Organoboranr-Catalyzed anti-Markownikoff Hydration of Olefins
-
A new, catalytic procedure for the anti-Markownikoff hydration of olefins in the presence of organoborane catalyst and dichloroaluminum hydride under dry air has been described.
- Maruoka, Keiji,Sano, Hiromi,Shinoda, Kiyotaka,Yamamoto, Hisashi
-
-
- Hydroboration. 61. Diisopinocampheylborane of High Optical Purity. Improved Preparation and Asymmetric Hydroboration of Representative Cis-Disubstituted Alkenes
-
The convenient preparation of diisopinocampheylborane of high enentiomeric purity (99.1percent) utilizing the commercially available relatively stable borane-methyl sulfide and α-pinene of 92percent enantiomeric purity is described.Methyl sulfide liberated in the hydroboration step interferes with the equilibration needed to improve the optical purity of the reagent.However, this difficulty is readily overcome by removal of methyl sulfide under vacuum following hydroboration of the α-pinene.The raegent is then equilibrated in THF with 15percent excess α-pinene at 0 deg C for3 days.During this equilibration period, the major isomer becomes incorporated selectively into the reagent.This high optical purity diisopinocampheylborane has been utilized for asymmetric hydroboration of representative cis-disubstituted alkenes such as cis-2-butene, cis-3-hexene, cis-2-pentene, norbornene, norbornadiene, cis-4,4-dimethyl-2-pentene, and cis-propenylbenzene.Oxidation of the intermediate organoboranes provides the coprresponding alcohols in enantiomeric purities of 60-98percent.
- Brown, Herbert C.,Desai, Manoj C.,Jadhav, Prabhakar K.
-
p. 5065 - 5069
(2007/10/02)
-
- Hydroboartion. 62. Monoisopinocampheylborane, an Excellent Chiral Hydroborating Agent for Trans-Disubstituted and Trisubstituted Alkenes. Evidenece for a Strong Steric Dependence in Such Asymmetric Hydroborations
-
Monoisopinocampheylborane (IpcBH2), the first monoalkylborane chiral hydroborating agent, is capable of reacting with olefins of varying stuctural and steric requiments to produce, in most cases, clean dialkylboranes.IpcBH2 achieves the asymmetric hydroboration of trans-disubstituted and trisubstituted olefins with exceptionally high asymmetric induction.The product alcohols, produced by oxidation of the intermediate organoboranes, exhibit enantiomeric purities in the range of 53-100percent ee and reveal the same absolute configuration.Enantiomeric purities of the products increase with increasing steric requirements of the alkyl or phenyl substituent in the trans-disubstituted or trisubstituted alkene.
- Brown, Herbert C.,Jadhav, Prabhakar K.,Mandal, Arun K.
-
p. 5074 - 5083
(2007/10/02)
-
- Cyanidation Products of Organoboranes Derived from Linalyl Acetate
-
The seven-membered cyclic borane obtained from the reaction of linalyl acetate and thexylborane loses 2,3-dimethylbut-2-ene, and the resulting dialkulborane gives an alcohol on treatment with sodium syanide, followed by trifluoroacetic anhydride and oxidation.The structure is confirmed by synthesis.The generality of this reaction was investigated but, of the dialkylboranes examined, only 9-borabicyclononane participated in the cyanidation procedure.A simple synthesis of menthone is presented
- Murphy, Roger,Prager, Rolf H.
-
p. 143 - 150
(2007/10/02)
-
