- Catalytic δ-hydroxyalkynone rearrangement in the stereoselective total synthesis of centrolobine, engelheptanoxides A and C and analogues
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A catalytic stereoselective total synthesis of centrolobine and engelheptanoxides A and C has been completed via a metal-free catalytic δ-hydroxyalkynone rearrangement to 2,3-dihydro-4H-pyran-4-one and diastereoselective hydrogenation to the all syn-2,4,6-trisubstituted pyran strategy. The onliest required chirality was introduced by Jacobsen kinetic resolution, which further directed the diastereoselective hydrogenation. A first stereoselective synthesis of engelheptanoxide A is also accomplished. The analogues and derivatives of centrolobine and engelheptanoxides prepared were evaluated for antitubercular activity against M. tuberculosis H37Rv ATCC 27294.
- Ahmad, Mohammad N.,Chopra, Sidharth,Fernandes, Rodney A.,Kumar, Praveen
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- Heterocyclization involving benzylic C(sp3)-H functionalization enabled by visible light photoredox catalysis
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A general and efficient method for heterocyclization involving benzylic C(sp3)-H functionalization enabled by visible light photoredox catalysis to access a wide range of structurally diverse oxygen as well as nitrogen heterocycles up to a gram scale is reported. The potential application of this new methodology is demonstrated by the total synthesis of (-)-codonopsinine and (+)-centrolobine. Herein it is proposed that selectfluor, unlike a fluorinating reagent, acts as an oxidative quencher and a hydrogen radical acceptor.
- Pandey, Ganesh,Laha, Ramkrishna,Mondal, Pradip Kumar
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supporting information
p. 9689 - 9692
(2019/08/15)
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- Convergent total synthesis of (±) myricanol, a cyclic natural diarylheptanoid
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Myricanol 1, a constituent of Myrica species, has been reported to lower the levels of the microtubule-associated protein tau (MAPT), whose accumulation plays an important role in some neurodegenerative diseases, such as Alzheimer's disease (AD). Herein w
- Bochicchio,Schiavo,Chiummiento,Lupattelli,Funicello,Hanquet,Choppin,Colobert
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p. 8859 - 8869
(2018/11/30)
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- Flexible Analogues of Azaindole DYRK1A Inhibitors Elicit Cytotoxicity in Glioblastoma Cells
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DYRK1A is a novel target for epidermal growth factor receptor (EGFR)-dependent glioblastoma and it represents a promising strategy for cancer therapy. DYRK1A inhibition has been found to promote EGFR degradation in glioblastoma cells by triggering endocyt
- Zhou, Qingqing,Reekie, Tristan A.,Abbassi, Ramzi H.,Venkata, Dinesh Indurthi,Font, Josep S.,Ryan, Renae M.,Rendina, Louis M.,Munoz, Lenka,Kassiou, Michael
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p. 789 - 797
(2018/09/11)
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- Combining spiro-fused cyclohexadienone – tetrahydrofuran ring system with glycine: Asymmetric synthesis of a new class of α-amino acid derivatives
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Herein, we present the asymmetric synthesis of spiro-fused cyclohexadienone – tetrahydrofuran-embedded glycine derivatives as a new class of nonproteinogenic α-amino acid derivatives. Starting from commercially available 2-allylphenols, key β-hydroxy-α-am
- Devi, Runjun,Das, Sajal Kumar
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supporting information
p. 2281 - 2283
(2018/05/23)
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- Lipase-catalyzed resolution of 1-[4-(benzyloxy)phenyl]hex-5-en-3-ol: Synthesis of (-)-centrolobine
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A practical and efficient method for the preparation of homoallylic alcohol and its successful enzymatic resolution has been developed. This lipase-catalyzed resolution process has been optimized with respect to different lipases and solvents. Moreover, M
- Tadiparthi, Krishnaji,Raghavendra,Kamal, Ahmed
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p. 2321 - 2326
(2017/10/06)
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- Lewis Acid Mediated "endo-dig" Hydroalkoxylation-Reduction on Internal Alkynols for the Stereoselective Synthesis of Cyclic Ethers and 1,4-Oxazepanes
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Lewis acid mediated 5/6/7-endo-dig hydroalkoxylation-reduction cascade on internal alkynols gave an expedient, stereoselective synthesis of cyclic ethers and 1,4-oxazepanes. The strategy has been extended to the first examples of hydroalkoxylation-alkyne
- Gharpure, Santosh J.,Vishwakarma, Dharmendra S.,Nanda, Santosh K.
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supporting information
p. 6534 - 6537
(2017/12/26)
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- Synthesis of tetrahydropyranyl diarylheptanoids from Dioscorea villosa
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Concise syntheses of four tetrahydropyranyl diarylheptanoids isolated from Dioscorea villosa have been described. The key features include Prins cyclization to construct the tetrahydropyran cores, Keck asymmetric allylation, and Mitsunobu inversion. Optimization of the Prins cyclization conditions in order to minimize racemization has been described. Our syntheses also confirmed the absolute stereochemistry of the natural products.
- Kantee, Kawalee,Rukachaisirikul, Vatcharin,Tadpetch, Kwanruthai
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supporting information
p. 3505 - 3509
(2016/07/15)
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- Stereoselective total synthesis of (3S,5S)-1,7-bis(4-hydroxyphenyl)heptane-3,5-diol, (3S,5S)-alpinikatin, and its diastereoisomers
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Stereoselective synthesis of the diarylheptanoids, (3S,5S)-1,7-bis(4-hydroxyphenyl)heptane-3,5-diol (1), (3S,5S)-alpinikatin (3), and their diastereoisomers (2 and 4, resp.), was achieved from readily available 4-hydroxybenzaldehyde. The synthetic sequenc
- Venkatesham, Kunuru,Purushotham Reddy, Sudina,Chinnababu, Baggu,Suresh Babu, Katragadda
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p. 1307 - 1314
(2015/09/28)
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- The first stereoselective total synthesis of naturally occurring, bioactive (3R,5R)-1-(4-hydroxyphenyl)-7-phenylheptane-3,5-diol and the synthesis of its enantiomer
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The first stereoselective total synthesis of the naturally occurring anti-emetic diarylheptanoid (3R,5R)-1-(4-hydroxyphenyl)-7-phenylheptane-3,5-diol (1) was accomplished starting from 4-hydroxybenzaldehyde and involving a Sharpless kinetic resolution and
- Reddy, Parigi Raghavendar,Sudhakar, Chithaluri,Kumar, Jayprakash Narayan,Das, Biswanath
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p. 289 - 295
(2013/03/28)
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- A natural product inspired tetrahydropyran collection yields mitosis modulators that synergistically target CSE1L and tubulin
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A Prins cyclization between a polymerbound aldehyde and a homoallylic alcohol served as the key step in the synthesis of tetrahydropyran derivatives. A phenotypic screen led to the identification of compounds that inhibit mitosis (as seen by the accumulation of round cells with condensed DNA and membrane blebs; see picture). These compounds were termed tubulexins as they target the CSE1L protein and the vinca alkaloid binding site of tubulin.
- Voigt, Tobias,Gerding-Reimers, Claas,Tran, Tuyen Thi Ngoc,Bergmann, Sabrina,Lachance, Hugo,Sch?lermann, Beate,Brockmeyer, Andreas,Janning, Petra,Ziegler, Slava,Waldmann, Herbert
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supporting information
p. 410 - 414
(2013/02/23)
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- The first stereoselective total synthesis of a naturally occurring bioactive diarylheptanoid, (3R,6E)-1,7-bis(4-hydroxyphenyl)hept-6-en-3-ol, through two different approaches
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The stereoselective total synthesis of a naturally occurring bioactive diarylheptanoid, (3R,6E)-1,7-bis(4-hydroxyphenyl)hept-6-en-3-ol, has been accomplished starting from 4-hydroxybenzaldehyde through two different approaches involving Wittig olefination
- Kashanna, Jajula,Jangili, Paramesh,Kumar, Rathod Aravind,Das, Biswanath
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p. 1666 - 1671
(2012/11/07)
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- Stereoselective total synthesis of dodoneine
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A simple and highly efficient stereoselective total synthesis of dodoneine (1), a naturally occurring bioactive 5,6-dihydro-2H-pyran-2-one, was achieved. The synthesis involved Keck's asymmetric allylation, iodine-induced electrophilic cyclization, and Gr
- Chinnababu, Baggu,Reddy, Sudina Purushotham,Rao, Chitturi Bhujanga,Rajesh, Karuturi,Venkateswarlu, Yenamandra
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experimental part
p. 1960 - 1966
(2010/12/25)
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- The biomimetic synthesis and final structure determination of (+)- and (-)-centrolobine, naturally occurring diarylheptanoid 2,6-cis-disubstituted tetrahydro-2H-pyrans
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The enantiomerically pure title compounds were prepared by oxidative cyclization of their optically active diarylheptanoid precursors. The approach is considered as a biomimetic phenol oxidation via an intermediate quinone methide. The absolute configuration of the precursors is retained, and the transition state adopts the sterically most favorable diequatorial arrangement of the 2,6-substituents to afford the cis-configured natural products. The outcome unambiguously establishes the absolute configurations and the correlation with the chiroptical data. In addition, a problem of regioisomerism that had not been discussed before was solved, and the original assignment of the position of the MeO group in the natural centrolobines could be confirmed. As such the results are the experimental evidence for the corrections of long-term inconsistencies we had postulated in an earlier review article.
- Rogano, Frank,Rueedi, Peter
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experimental part
p. 1281 - 1298
(2010/09/12)
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- Stereoselective total synthesis of dodoneine
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The stereoselective total synthesis of the naturally occurring bioactive dihydropyranone dodoneine has been achieved involving the Sharpless asymmetric epoxidation, 1,3-syn diastereoselective reduction and Grubb's ring-closing metathesis as key steps.
- Das, Biswanath,Suneel, Kanaparthy,Satyalakshmi, Gandham,Kumar, Duddukuri Nandan
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experimental part
p. 1536 - 1540
(2009/12/03)
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- Lewis base-promoted hydrosilylation of cyclic malonates: Synthesis of β-substituted aldehydes and γ-substituted amines
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The Lewis base-promoted hydrosilylation of cyclic malonates provides a convenient synthesis of β-substituted aldehydes. No over-reduction to the primary alcohol is observed as the aldehyde functionality is protected until a subsequent hydrolysis step. The
- Frost, Christopher G.,Hartley, Benjamin C.
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supporting information; experimental part
p. 3599 - 3602
(2009/09/05)
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- TETRACYCLIC INHIBITORS OF FATTY ACID AMIDE HYDROLASE
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Certain tetracyclic compounds are described, which may be used in pharmaceutical compositions and methods for treating disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity. Thus, the compounds may be administered to treat, e.g., anxiety, pain, inflammation, sleep disorders, eating disorders, or movement disorders (such as multiple sclerosis).
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Page/Page column 39
(2009/01/20)
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- Ruthenium-catalyzed tandem allylic substitution/isomerization: A direct route to propiophenones from cinnamyl chloride derivatives
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A tandem nucleophilic substitution/redox isomerization catalyzed by a single ruthenium catalyst leads to the direct transformation of allylic chlorides into propiophenones. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.
- Helou, Marion,Renaud, Jean-Luc,Demerseman, Bernard,Carreaux, Francois,Bruneau, Christian
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p. 929 - 931
(2008/12/20)
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- Structure-activity relationships of α-ketooxazole inhibitors of fatty acid amide hydrolase
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A systematic study of the structure-activity relationships of 2b (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed targeting the C2 acyl side chain. A series of aryl replacements or substituents for the terminal phenyl group provided effective inhibitors (e.g., 5c, aryl = 1-napthyl, K, - 2.6 nM), with 5hh (aryl -3-ClPh, Ki = 900 pM) being 5-fold more potent than 2b. Conformationally restricted C2 side chains were examined, and many provided exceptionally potent inhibitors, of which 11j (ethylbiphenyl side chain) was established to be a 750 pM inhibitor. A systematic series of heteroatoms (O, NMe, S), electron-withdrawing groups (SO, SO2), and amides positioned within and hydroxyl substitutions on the linking side chain were investigated, which typically led to a loss in potency. The most tolerant positions provided effective inhibitors (12p, 6-position S, Ki = 3 nM, or 13d, 2-position OH, Ki = 8 nM) comparable in potency to 2b. Proteome-wide screening of selected inhibitors from the systematic series of >100 candidates prepared revealed that they are selective for FAAH over all other mammalian serine proteases.
- Hardouin, Christophe,Kelso, Michael J.,Romero, F. Anthony,Rayl, Thomas J.,Leung, Donmienne,Hwang, Inkyu,Cravatt, Benjamin F.,Boger, Dale L.
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p. 3359 - 3368
(2008/02/13)
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- Suppression of epimerization due to selectivity leakage: An application towards the total synthesis of (-)-centrolobine
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An InCl3-mediated Prins cyclization of homoallylic alcohols with aldehydes has been established. The enantioselectivities of the trisubstituted tetrahydropyrans are almost retained through the suppression of epimerization. The synthetic value o
- Lee, Cheng-Hsia Angeline,Loh, Teck-Peng
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p. 1641 - 1644
(2007/10/03)
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- METHOD FOR HYDROGENATION OF α,β-UNSATURATED CARBONYL COMPOUNDS
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A method for the chemoselective hydrogenation of a,? unsaturated carbonyl compounds is disclosed, in which compounds of general formula (I), where R1 = H, branched, unbranched, saturated or unsaturated 1-30C hydrocarbon group which may have suitable substituents and the hydrocarbon group may have one or more heteroatoms in the chain, aryl or heteroaryl group which can have suitable substituents, R2, R3 and R4 independently = H, F, Cl, Br, I, OH, CN, NO2, NO, SO2, SO3, amino, mono- and di-(C1-C24) alkyl substituted amino, mono- and di-(C5-C20) aryl substituted amino, imino, phosphono, phosphonato, phosphinato, phospho, phosphino, a branched, unbranched, saturated or unsaturated 1-30C hydrocarbon group which may have suitable substituents and the hydrocarbon group may have one or more heteroatoms in the chain, aryl or heteroaryl group which can have suitable substituents, each of R2, R3 and R4 can form a 5- or 6-membered ring or annelated 5-and/or 6-membered rings which can be aromatic, alicyclic, heteroaromatic or heteroalicyclic and have up to 4 substituents, are reacted with a hybrid donor to form a compound of general formula (II) in which R1, R2, R3 and R4 are as above. Said method permits the selective hydrogenation of a,? unsaturated aldehydes and ketones without the use of metal catalysts.
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Page/Page column 11
(2008/06/13)
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- Two successive one-pot reactions leading to the expeditious synthesis of (-)-centrolobine
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A very short and efficient synthesis of (-)-centrolobine has been achieved by using two successive one-pot reactions. The first sequence involves a cross-metathesis reaction/hydrogenation/lactonization and the second sequence is a Grignard addition/reduct
- Boulard, Lucie,Bouzbouz, Samir,Cossy, Janine,Franck, Xavier,Figadère, Bruno
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p. 6603 - 6605
(2007/10/03)
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- A metal-free transfer hydrogenation: Organocatalytic conjugate reduction of α,β-unsaturated aldehydes
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Impressive tolerance is displayed in the efficient and chemoselective organocatalytic transfer hydrogenation of α,β-unsaturated aldehydes in the presence of a Hantzsch dihydropyridine and a catalytic amount of dibenzylammonium trifluoroacetate (see scheme). Various sensitive functional groups such as the nitro, cyano, alkenyl, and benzyloxy groups survive these reaction conditions.
- Yang, Jung Woon,Hechavarria Fonseca, Maria T.,List, Benjamin
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p. 6660 - 6662
(2007/10/03)
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- Initial structure-activity relationship of a novel class of nonpeptidyl GnRH receptor antagonists: 2-arylindoles
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A nonpeptidyl GnRH receptor antagonist (1), with a unique 2-arylindole core, was identified through the Merck in-house screening for binding affinity on the rat GnRH receptor. SAR studies directed toward the alkoxy-ethanolamine and 2-aryl groups resulted in a simpler lead structure with improved activity. This compound 50 exhibits a 60-fold improvement in binding activity over our initial lead 1.
- Chu, Lin,Hutchins, Jennifer E.,Weber, Ann E.,Lo, Jane-Ling,Yang, Yi-Tien,Cheng, Kang,Smith, Roy G.,Fisher, Michael H.,Wyvratt, Matthew J.,Goulet, Mark T.
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p. 509 - 513
(2007/10/03)
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- Nonpeptidic HIV protease inhibitors possessing excellent antiviral activities and therapeutic indices. PD 178390: A lead HIV protease inhibitor
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With the insight generated by the availability of X-ray crystal structures of various 5,6-dihydropyran-2-ones bound to HIV PR, inhibitors possessing various alkyl groups at the 6-position of 5,6-dihydropyran-2-one ring were synthesized. The inhibitors pos
- Vara Prasad,Boyer, Frederick E.,Domagala, John M.,Ellsworth, Edmund L.,Gajda, Christopher,Hamilton, Harriet W.,Hagen, Susan E.,Markoski, Larry J.,Steinbaugh, Bruce A.,Tait, Bradley D.,Humblet, Christine,Lunney, Elizabeth A.,Pavlovsky, Alexander,Rubin, John R.,Ferguson, Donna,Graham, Neil,Holler, Tod,Hupe, Donald,Nouhan, Carolyn,Tummino, Peter J.,Urumov,Zeikus, Eric,Zeikus, Greg,Gracheck, Stephen J.,Saunders, James M.,Vanderroest, Steven,Brodfuehrer, Joanne,Iyer,Sinz,Gulnik, Sergei V.,Erickson, John W.
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p. 2775 - 2800
(2007/10/03)
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- THE BIOSYNTHESIS OF SCELETIUM ALKALOIDS IN SCELETIUM SUBVELUTINUM L. BOLUS
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Six Sceletium (Mesembrine) alkaloids (1)-(6) are identified, together with N,N-dimethyltyramine (10), as constituents of Sceletium subvelutinum.The alkaloids (1)-(6) incroporate label from tyramine and 3-(-4-hydroxyphenyl)propionic acid (13) as expected; notably 3-(-4-hydroxyphenyl)propanal (15) is a more efficient alkaloid precursor than is the acid (13) and the aldehyde is deduced to be a key intermediate in the biosynthesis of Sceletium alkaloids.The N-methylamine (21) is an important late intermediate in the biosynthesis of Sceletium alkaloids, or is closely related to that intermediate.The amine (2) is less efficiently incorporated than (22)=(21) is.
- Herbert, Richard B.,Kattah, Abdullah E.
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p. 7105 - 7118
(2007/10/02)
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- Methods for the Construction of Linear 1,7-Diarylheptanoids; Synthesis of Di-O-methylcentrolobol and Precursors (Synthetic and Biosynthetic) to the meta,meta-Bridged Biphenyls Myricanol and Myricanone
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1,7-diarylheptanoids are a varied natural product class in which 'linear' types appear to be biosynthetic precursors to macro(carbo)cyclic (3), macro(oxa)cyclic (4), and condensed polycyclic (5) examples.Various methods (suitable for radiolabelling) are described for constructing 'linear' diarylheptanoids, including Grignard couplings (employing activated magnesium) with arylpropanals and oxazonium salts (11a), (11h), (15a), and (15b)> and dithian alkylation (15c)>.Alkyl-lithium treatment of the benzyloxydithian (19b) gave 1,2,3-triphenylcyclopropane.Syntheses via trialkylcyanoborates were frustrated by disproportionation of the intermediate trialkylboranes.The diarylheptanoids synthesised (11a-h) and (15a-e) include synthetic and biosynthetic precursors to meta,meta-bridged biphenyls and related macrocyclic ethers.
- Henley-Smith, Peter,Whiting, Donald A.,Wood, Andrew F.
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p. 614 - 622
(2007/10/02)
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