- Conformationally Controlled Linear and Helical Hydrocarbons Bearing Extended Side Chains
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Conformationally controlled flexible molecules are ideal for applications in medicine and materials, where shape matters but an ability to adapt to multiple and changing environments is often required. The conformation of flexible hydrocarbon chains bearing contiguous methyl substituents is controlled through the avoidance of syn-pentane interactions: alternating syn-anti isomers adopt a linear conformation while all-syn isomers adopt a helical conformation. From a simple diamond lattice analysis, larger substituents, which would be required for most potential applications, result in significant and unavoidable syn-pentane interactions, suggesting substantially reduced conformational control. Through a combination of computation, synthesis, and NMR analysis, we have identified a selection of substitution patterns that allow large groups to be incorporated on conformationally controlled linear and helical hydrocarbon chains. Surprisingly, when the methyl substituents of alternating syn-anti hydrocarbons are replaced with acetoxyethyl groups, the main chain of almost 95% of the population of molecules adopt a linear conformation. Here, the side chains adopt nonideal eclipsed conformations with the main chain, thus minimizing syn-pentane interactions. In the case of all-syn hydrocarbons, concurrent removal of some methyl groups on the main chain adjacent to the large substituents is required to maintain a high population of molecules adopting a helical conformation. This information can now be used to design flexible hydrocarbon chains displaying functional groups in a defined relative orientation for multivalent binding or cooperative reactivity, for example, in targeting the interfaces defined by disease-relevant protein-protein interactions.
- Aggarwal, Varinder K.,Butts, Craig P.,Davy, Matthew,Dutton, Oliver J.,Guo, Lin,Kucukdisli, Murat,Myers, Eddie L.,Wagnières, Olivier
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p. 16682 - 16692
(2021/10/21)
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- STING AGONISTS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same for the modulation of STING, and the treatment of STING-mediated disorders.
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Paragraph 00687
(2020/07/14)
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- Grubbs Catalysts Immobilized on Merrifield Resin for Metathesis of Leaf Alcohols by using a Convenient Recycling Approach
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Three new types of heterogeneous catalysts were prepared using a facile approach by the immobilization of Grubbs catalysts on PEGylated Merrifield resin. One of the immobilized catalysts was more efficient than the free catalyst for the metathesis of leaf alcohols in conversion and selectivity and was reused repeatedly (up to 5 cycles) with only a slight loss of activity (10.5 %). The long-chain PEGylated linker provided an appropriate distance between the resin and the catalytic center so that the ruthenium catalysts acted as the free catalyst.
- Xia, Liang,Peng, Tao,Wang, Gang,Wen, Xiaoxue,Zhang, Shouguo,Wang, Lin
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- Compounds and Their Use in Treating Cancer
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The specification generally relates to compounds of Formula (I): and pharmaceutically acceptable salts and prodrugs thereof, where R1, R4, R5, R6, R7, Linker, X, Y, A, G, D and E have any of the meanings defined herein. This specification also relates to the use of such compounds and pharmaceutically acceptable salts and prodrugs thereof in methods of treatment of the human or animal body, for example in prevention or treatment of cancer. This specification also relates to processes and intermediate compounds involved in the preparation of such compounds and to pharmaceutical compositions containing them.
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Paragraph 0710-0712
(2019/07/10)
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- Synthesis of the C18–C26 tetrahydrofuran-containing fragment of amphidinolide C congeners via tandem asymmetric dihydroxylation and SN2 cyclization
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The C18–C26 fragment of amphidinolide C congeners has been synthesized starting from methyl acetoacetate in 14 steps in >17.0% overall yield. The C20 stereogenic center was secured by asymmetric hydrogenation of a β-keto ester and the configuration at both C23 and C24 was introduced by asymmetric dihydroxylation (AD). The trans-2,5-disubstituted tetrahydrofuran ring was assembled via the tandem AD–SN2 sequence. The latter protocol could be employed for accessing the corresponding cis-2,5-disubstituted tetrahydrofuran rings from the same alkene substrates simply by choosing a suitable AD ligand. Moreover, functional group compatibility was observed for the Ru(II)-catalyzed hydrogenation of β-keto esters and the Pd(0)–Cu(I)-catalyzed Sonogashira cross-coupling reaction. These findings should be valuable for general synthetic design and application.
- Su, Ye-Xiang,Dai, Wei-Min
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p. 1546 - 1554
(2018/02/26)
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- Singlet oxygen-mediated synthesis of bis -spiroketals found in azaspiracids
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Conversion of a simple furan into the ABCD-ring skeleton of the azaspiracids via a singlet oxygen-initiated one-pot process has been accomplished.
- Triantafyllakis, Myron,Tofi, Maria,Montagnon, Tamsyn,Kouridaki, Antonia,Vassilikogiannakis, Georgios
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supporting information
p. 3150 - 3153
(2014/06/23)
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- Synthesis and biological evaluation of new cytotoxic indazolo[4,3-gh] isoquinolinone derivatives
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A series of indazolo[4,3-gh]isoquinolinones derivatives have been synthesized to decrease cardiotoxic side effects in comparison to Mitoxantrone. The antiproliferative effects of different side chains were investigated and tested on at least four different cell lines of cervix, ovarian, CNS, NSCLC (non-small-cell lung cancer) and colon carcinoma. In addition to antiproliferative activities, influence on cell cycle and intercalation behavior have been tested.
- Shahabi, Manochehr,Schirmer, Eva,Shanab, Karem,Leepasert, Theerachart,Ruzicka, Jana,Holzer, Wolfgang,Spreitzer, Helmut,Aicher, Babette,Schmidt, Peter,Blumenstein, Lars,Müller, Gilbert,Günther, Eckhard
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p. 1846 - 1852
(2013/04/10)
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- Synthesis of dipeptide isosteres by cross-metathesis
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This work describes the attachment of two amino acid derivatives by olefin cross-metathesis using Grubbs' second generation catalyst. They were connected at the carboxyl termini. In addition, a cyclic dilactam scaffold was used, which reacted with only a
- Enholm, J. Eric,Low, Tammy,Cooper, Daniel,Ghivirija, Ion
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p. 6920 - 6927
(2012/08/29)
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- Synthesis, redox properties, and conformational analysis of vicinal disulfide ring mimics
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A vicinal disulfide ring (VDR) results from disulfide-bond formation between two adjacent cysteine residues. This eight-membered ring is a rare motif in protein structures and is functionally important to those few proteins that posses it. This article focuses on the construction of strained and unstrained VDR mimics, discernment of the preferred conformation of these mimics, and the determination of their respective disulfide redox potentials.
- Ruggles, Erik L.,Deker, P. Bruce,Hondal, Robert J.
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experimental part
p. 1257 - 1267
(2009/05/07)
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- MACROCYCLIC COMPOUNDS USEFUL AS INHIBITORS OF KINASES AND HSP90
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Disclosed are macrocyclic compounds of formulae I-V,which are analogs of the pochonin resorcylic acid lactones, and processes for the preparation of the compounds. The compounds disclosed are useful as inhibitors of kinases and Heat Shock Protein 90 (HSP 90). Also disclosed are pharmaceutical compositions comprising an effective kinase-inhibiting amount or an effective HSP90-inhibiting amount of the compounds and methods for the treatment of disorders that are mediated by kinases and HSP90.
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Page/Page column 146
(2010/11/30)
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- A biosynthetically-inspired synthesis of the tetrahydrofuran core of obtusallenes II and IV
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Sharpless asymmetric dihydroxylation was regioselective for the frans olefin in an E vs Z vs terminal triene substrate. To test a biosynthetic hypothesis, the resulting diol underwent diastereoselective bromoetherification to provide the des-chloro core o
- Braddock, D. Christopher,Bhuva, Roshni,Millan, David S.,Perez-Fuertes, Yolanda,Roberts, Craig A.,Sheppard, Richard N.,Solanki, Savade,Stokes, Elaine S. E.,White, Andrew J. P.
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p. 445 - 448
(2007/10/03)
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- Synthesis and properties of disulfide-bond containing eight-membered rings
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The cyclocystine ring structure (CRS, 3), which results from a disulfide-bond between adjacent cysteine residues, is a rare motif in protein structures and is functionally important to those few proteins that posses it. This letter will focus on the const
- Ruggles, Erik L.,Hondal, Robert J.
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p. 4281 - 4284
(2007/10/03)
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- Stereoselective synthesis of (-)-jimenezin
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Total synthesis of jimenezin was achieved via radical cyclization of β-alkoxyacrylate and β-alkoxyvinyl sulfoxide intermediates and intramolecular olefin metathesis reaction.
- Hwang, Cheol Hee,Keum, Gyochang,Sohn, Kyoung Il,Lee, Dong Hoon,Lee, Eun
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p. 6621 - 6623
(2007/10/03)
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- Self-selection in olefin cross-metathesis: The effect of remote functionality
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(Chemical Equation Presented) Olefin cross-metathesis (CM) is potentially an attractive method for generating dynamic combinatorial libraries (DCLs). In order for the CM reaction to be useful for DCL production, the course of the reaction and product dist
- McNaughton, Brian R.,Bucholtz, Kevin M.,Camaano-Moure, Ana,Miller, Benjamin L.
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p. 733 - 736
(2007/10/03)
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- Synthesis and Characterization of Potent Bivalent Amyloidosis Inhibitors That Bind Prior to Transthyretin Tetramerization
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The misfolding of transthyretin (TTR), including rate-limiting tetramer dissociation and partial monomer denaturation, is sufficient for TTR misassembly into amyloid and other abnormal quaternary structures associated with senile systemic amyloidosis, fam
- Green, Nora S.,Palaninathan, Satheesh K.,Sacchettini, James C.,Kelly, Jeffery W.
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p. 13404 - 13414
(2007/10/03)
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- A convergent total synthesis of (-)-mucocin: An acetogenin from Annonaceae
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A total synthesis of the Annonaceous acetogenin mucocin has been accomplished. The synthesis follows a convergent strategy, wherein at a very late stage the left part of the molecule is connected with the right part. The key reaction is the stereocontrolled addition of an organomagnesium compound 2 to the aldehyde 3. The THP ring of mucocin is build by a 6-endo epoxide cyclization of an epoxyacetonide precursor (16 → 17). The new modular synthetic approach developed herein should be useful for the synthesis of other related natural products as well as pharmacologically interesting analogues.
- Hoppen, Sabine,Baeurle, Stefan,Koert, Ulrich
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p. 2382 - 2396
(2007/10/03)
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- Preparation of 3-alkylpyridines. Formal total synthesis of haliclamines A and B
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The formal total synthesis of two sponge alkaloids Haliclamines A and B is achieved through the preparation of 3-alkylpyridines 3, 4 and 5 via an advanced common intermediate 6. (C) 2000 Elsevier Science Ltd.
- Baldwin, Jack E.,James, Delyth A.,Lee, Victor
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p. 733 - 736
(2007/10/03)
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- Model studies of the overall 5-endo-trig iodocyclization of homoallylic alcohols
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Overall 5-endo-trig iodocyclizations of homoallylic alcohols, with a range of substitution patterns, leading to β-iodotetrahydrofurans are usually highly efficient and stereoselective when carried out in anhydrous acetonitrile in the presence of sodium hydrogen carbonate. Such cyclizations, which are not exceptions to Baldwin's rules as they are electrophile-driven, appear to proceed via a well-ordered chair-like transition state. The iodine can be replaced by hydroxy, acetoxy and azide groups.
- Bedford, Simon B.,Bell, Kathryn E.,Bennett, Frank,Hayes, Christopher J.,Knight, David W.,Shaw, Duncan E.
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p. 2143 - 2153
(2007/10/03)
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- Synthesis of (tetrahydrofiiranyl)tetrahydrofurans via radical cyclization of bis(-alkoxyacrylates)
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Radical cyclizations of bis(-alkoxyacrylates) obtained from. (3R, 4R)- and mes0-l, 6-dibromohexane-3, 4-diol proceed to form a C2-symmetric and a nieso (tetrahydrofuranyl)tetrahydrofuran derivative. The Royal Society of Chemistry 1999.
- Lee, Eun,Song, Ho Young,Kirn, Hee Jo
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p. 3395 - 3396
(2007/10/03)
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- Design, synthesis, and conformational analysis of a proposed type I β- turn mimic
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In an effort to design a dipeptide structural mimic of protein and peptide β-turns, we have prepared and evaluated the conformation of derivatives of the novel, highly constrained ten-membered lactam, (3S,10S)- (6E)-2-azacyclodec-6-enone (1). A synthetic
- Fink, Brian E.,Kym, Phil R.,Katzenellenbogen, John A.
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p. 4334 - 4344
(2007/10/03)
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- A modular approach to nonracemic cyclo-BINOLs. Preparation of symmetrically and unsymmetrically substituted ligands
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A new series of substituted cyclo-BINOLs is described, constructed using individually fashioned naphthol units which are tethered and oxidized to arrive at nonracemic materials.
- Lipshutz, Bruce H.,Shin, Young-Jun
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p. 7017 - 7020
(2007/10/03)
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- A potentially general intramolecular biaryl coupling approach to optically pure 2,2'-BINOL analogs
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Tethering of two equivalents of mono-protected 2,7-dihydroxynaphthalene gives an intermediate which allows for eventual copper-catalyzed intramolecular biaryl coupling to afford a new nonracemic BINOL documenting a new strategy to modified binaphthyl liga
- Lipshutz, Brace H.,James, Brian,Vance, Shelly,Cairico, Isaac
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p. 753 - 756
(2007/10/03)
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- Syntheses and NMR analyses of the eight geometric isomers of 3,6,8-dodecatrien-1-ol, subterranean termite trail pheromone
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Eight geometric isomers of 3,6,8-dodecatrien-1-ol 1, the trail-following pheromone of subterranean termites (Reticulitermes sp. Banks), were synthesized via a Wittig olefination reaction. The convergent syntheses of 1 consisted of a combination of two fragments, each containing an olefin with a fixed configuration, by formation of a third double bond to give a mixture of two geometric isomers. The mixtures of 1 were resolved by recycle high-performance liquid chromatography methods. 1H and 13C NMR peak assignments of the individual isomers were accomplished by homonuclear COSY, and one-bond CH correlation spectroscopy.
- Eya, Bryan K.,Otsuka, Toshikazu,Kubo, Isao,Wood, David L.
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p. 2695 - 2706
(2007/10/02)
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- Stereocontrolled construction of A.B.C.tricycle via transannular Diels-Alder reaction of 14-membered triene macrocycle
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The synthesis of the four acyclic trienes 11a, b and 20 a, b is reported.The tandem macrocyclization and stereoselective transannular Diels-Alder reaction of acyclic trienes 11b (trans-trans-cis) and 20b (trans-trans-trans) were observed in the presence of Cs2CO3 at 85 deg C to give tricycles 30 (TST) and 32 (CAT) respectively.However, treatment of acyclic trienes 11a (cis-trans-cis) and 20a (cis-trans-trans) under the same conditions yielded the 14-membered macrocycles 21 and 23, which were stereoselectively transformed at 250 deg C into tricycles 22 (CST) and 24 (CAT) respectively in excellent yield.
- Cantin, Michel,Xu, Yao-Chang,Deslongchamps, Pierre
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p. 2144 - 2152
(2007/10/02)
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- Molecules with Twist Bent Bonds. The Synthesis, Properties, and Reactions of trans-Bicyclohept-3-ene and Certain Methylated Derivatives
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trans-Bicyclohept-3-ene, 7-methyl-trans-bicyclohept-3-ene, and 7,7-dimethyl-trans-bicyclohept-3-ene have been synthesized.Comparison of their ease of oxidation with the ease of oxidation of the analogous cis-bicyclohept-3-enes has been made.Both the thermal and transition-metal complex promoted rearrangements of the trans-bicyclohept-3-enes have been studied.These systems thermally convert to the cis-bicyclohept-3-enes above 100 deg C and are catalytically rearranged at ambient temperature.Trans to cis isomerization alsooccurs at ambient temperature under photoinduced single electron transfer conditions.
- Gassman, Paul G.,Bonser, Steven M.,Mlinaric-Majerski, Kata
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p. 2652 - 2662
(2007/10/02)
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- Synthesis and Photoinduced Electron-Transfer Promoted Isomerization of 7,7-Dimethyl-trans-bicyclohept-3-ene
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The title compound, 1, is highly reactive (very sensitive to acid, and, thermally isomerized to the cis isomer 2, at 110 deg C); photosensitized isomerization of 1 to 2 is effected by the excited state of 1-cyanonaphthalene.
- Gassman, Paul G.,Mlinaric-Majerski, Kata
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p. 2397 - 2398
(2007/10/02)
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