- Click, Release, and Fluoresce: A Chemical Strategy for a Cascade Prodrug System for Codelivery of Carbon Monoxide, a Drug Payload, and a Fluorescent Reporter
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A chemical strategy was developed wherein a single trigger sets in motion a three-reaction cascade leading to the release of more than one drug-component in sequence with the generation of a fluorescent side product for easy monitoring. As a proof of conc
- De La Cruz, Ladie Kimberly C.,Benoit, Stéphane L.,Pan, Zhixiang,Yu, Bingchen,Maier, Robert J.,Ji, Xingyue,Wang, Binghe
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- Stereoselective Synthesis of Coreoside D and Determination of Its Absolute Configuration
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We report the stereoselective synthesis of (3 S)- and (3 R)-coreoside D. The conjugated diyne in the C1-C14 moiety was synthesized through two types of palladium-catalyzed cross-coupling reaction. The introduction of the glucopyranose was achieved by a gl
- Imaizumi, Ryoya,Ogawa, Narihito
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supporting information
p. 1409 - 1412
(2020/11/23)
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- Diboration of 3-substituted propargylic alcohols using a bimetallic catalyst system: access to (Z)-allyl, vinyldiboronates
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The diboration of substituted propargylic alcohols has been achieved using a bimetallic Pd/Cu catalyst system. Thein situformation of a pentrafluoroboronic acid intermediate sufficiently activates the C-O bond towards dual catalysis affording (Z)-allyl, vinyldiboronates stereoselectively.
- Peck, Cheryl L.,Nekvinda, Jan,Santos, Webster L.
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supporting information
p. 10313 - 10316
(2020/09/16)
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- Second-Generation Synthesis of the Northern Fragment of Mandelalide A: Role of π-Stacking on Sharpless Dihydroxylation of cis-Enynes
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The development of a π-stacking-based approach for increased stereoselectivity in Sharpless asymmetric and diastereomeric dihydroxylation of cis-enynes is disclosed. The use of neighboring, electron-rich benzoate esters proved key to the success of this process. Density functional theory study suggests that the substrate benzoate ester group rigidifies the dihydroxylation transition states by forming a favorable π-stacking interaction in both Major-TS and Minor-TS. The energetic preference for the Major-TS was found in part because of the favorable eclipsing conformation of the alkene substituent as opposed to the disfavored bisecting conformation found in the Minor-TS. The application to a second-generation synthesis of the C15-C24 northern portion of mandelalide A is demonstrated.
- Ghosh, Ankan,Brueckner, Alexander C.,Cheong, Paul Ha-Yeon,Carter, Rich G.
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p. 9196 - 9214
(2019/08/12)
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- Improved synthesis of 2,4,6-trialkylpyridines from 1,5-diketoalkanes: The total synthesis of Anibamine
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Many pyridine syntheses have been developed to date. In this study, we focused on pyridine synthesis with 1,5-diketone derivatives and hydroxylamine. Treatment of simple 1,5-diketoalkanes and hydroxylamine in basic or acidic conditions gave aldol adducts without any pyridine compounds. However, by screening the reaction conditions, we found that acidic conditions produced via the formation of oxime intermediates derived from 1,5-diketoalkanes allowed the formation of the corresponding pyridine derivatives. This is the first example of 2,4,6-trialkylpyridine synthesis from quite simple 1,5-diketoalkanes. In order to demonstrate the utility of the reaction, we demonstrated the synthesis of pyridine derivatives and the total synthesis of a 6-substituted pyridyl-natural product, anibamine. This was achieved by following the above methodology using a reported compound as the starting material to give the product in 12% yield.
- Miyakoshi, Takeru,Konno, Hiroyuki
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p. 2896 - 2905
(2019/03/21)
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- Stereoselective total synthesis and structural revision of the diacetylenic diol natural products strongylodiols H and I
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The stereoselective total synthesis of strongylodiol H and I has been accomplished. The synthetic procedure comprised the stereoselective reduction of a ketone functionality in an ene–yne–one employing CBS as a catalyst and a Cadiot–Chodkiewicz coupling r
- Gangadhar, Pamarthi,Ramakrishna, Sayini,Venkateswarlu, Ponneri,Srihari, Pabbaraja
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supporting information
p. 2313 - 2320
(2018/09/14)
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- An Atom-Economic and Stereospecific Access to Trisubstituted Olefins through Enyne Cross Metathesis Followed by 1,4-Hydrogenation
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The combination of intermolecular enyne cross metathesis and subsequent 1,4-hydrogenation opens a stereocontrolled and atom-economic access to trisubstituted olefins. By investigating different combinations of functionalized alkyne and alkene substrates, we found that the outcome (yield, E / Z ratio) of the Grubbs II-catalyzed enyne cross-metathesis step depends on the substrate's structure, the amount of the alkene (used in excess), and the (optional) presence of ethylene. In any case, the 1,4-hydrogenation, catalyzed by 1,2-dimethoxybenzene-Cr(CO) 3, proceeds stereospecifically to yield exclusively the E -products from both the E- and Z- 1,3-diene intermediates obtained by metathesis. A rather broad scope and functional group compatibility of the method is demonstrated by means of 15 examples.
- Ratsch, Friederike,Schmalz, Hans-Günther
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supporting information
p. 785 - 792
(2018/01/27)
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- A remarkably useful sulfur bridge as synthetic lever in an approach to Javanicin B
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A concise and efficient synthesis of a non-racemic advanced intermediate to the quassinoid javanicin B is disclosed. The strategy is centred on a triple diene-transmissive Diels-Alder cycloaddition to form the four rings of javanicin B. A sulfur bridge plays several crucial roles allowing an intramolecular cycloaddition to occur with complete stereoselectivity, controlling the stereochemical outcome of another cycloaddition, and transforming into a pivotal electrophile for the introduction of a particularly hindered methyl group.
- Dion, Amélie,Spino, Claude
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p. 894 - 919
(2017/07/27)
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- Activity-Based Probes for 15-Lipoxygenase-1
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Human 15-lipoxygenase-1 (15-LOX-1) plays an important role in several inflammatory lung diseases, such as asthma, COPD, and chronic bronchitis, as well as various CNS diseases, such as Alzheimer's disease, Parkinson's disease, and stroke. Activity-based probes of 15-LOX-1 are required to explore the role of this enzyme further and to enable drug discovery. In this study, we developed a 15-LOX-1 activity-based probe for the efficient activity-based labeling of recombinant 15-LOX-1. 15-LOX-1-dependent labeling in cell lysates and tissue samples was also possible. To mimic the natural substrate of the enzyme, we designed activity-based probes that covalently bind to the active enzyme and include a terminal alkene as a chemical reporter for the bioorthogonal linkage of a detectable functionality through an oxidative Heck reaction. The activity-based labeling of 15-LOX-1 should enable the investigation and identification of this enzyme in complex biological samples, thus opening up completely new opportunities for drug discovery.
- Eleftheriadis, Nikolaos,Thee, Stephanie A.,Zwinderman, Martijn R. H.,Leus, Niek G. J.,Dekker, Frank J.
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supporting information
p. 12300 - 12305
(2016/10/13)
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- Gold-Catalyzed Intramolecular Tandem Cyclization of Indole-Ynamides: Diastereoselective Synthesis of Spirocyclic Pyrrolidinoindolines
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A gold-catalyzed intramolecular tandem cyclization of indole-ynamide affords tetracyclic spirocyclic pyrrolidinoindoline bearing an all-carbon quaternary stereocentre in a single step; however, when the reaction was carried out in the presence of BF3·Et2O, the corresponding tricyclic spirocyclic pyrrolidinoindoline-based enones are produced through a key 1,5-hydride shift. The developed chemistry provides a diastereoselective and straightforward entry to structurally diverse polycylic pyrrolidinoindolines from indole-ynamides in one-pot reactions under mild conditions.
- Zheng, Nan,Chang, Yuan-Yuan,Zhang, Li-Jie,Gong, Jian-Xian,Yang, Zhen
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supporting information
p. 371 - 375
(2016/05/19)
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- 2-ACYLAMINOTHIAZOLES FOR THE TREATMENT OF CANCER
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The present invention relates to inhibitors of the oncogenic protein kinase ALK of formula (I) as herein described and pharmaceutical compositions thereof. The compounds of formula (I) are useful in the preparation of a medicament, in particular for the treatment of cancer.
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Page/Page column 82
(2015/01/16)
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- δ-deuterium isotope effects as probes for transition-state structures of isoprenoid substrates
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The biosynthetic pathways to isoprenoid compounds involve transfer of the prenyl moiety in allylic diphosphates to electron-rich (nucleophilic) acceptors. The acceptors can be many types of nucleophiles, while the allylic diphosphates only differ in the number of isoprene units and stereochemistry of the double bonds in the hydrocarbon moieties. Because of the wide range of nucleophilicities of naturally occurring acceptors, the mechanism for prenyltransfer reactions may be dissociative or associative with early to late transition states. We have measured δ-secondary kinetic isotope effects operating through four bonds for substitution reactions with dimethylallyl derivatives bearing deuterated methyl groups at the distal (C3) carbon atom in the double bond under dissociative and associative conditions. Computational studies with density functional theory indicate that the magnitudes of the isotope effects correlate with the extent of bond formation between the allylic moiety and the electron-rich acceptor in the transition state for alkylation and provide insights into the structures of the transition states for associative and dissociative alkylation reactions.
- Choi, Seoung-Ryoung,Breugst, Martin,Houk, Kendall N.,Poulter, C. Dale
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supporting information
p. 3572 - 3580
(2014/05/06)
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- Alkoxyboration: Ring-closing addition of B-O σ bonds across alkynes
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For nearly 70 years, the addition of boron-X σ bonds to carbon-carbon multiple bonds has been employed in the preparation of organoboron reagents. However, the significantly higher strength of boron-oxygen bonds has thus far precluded their activation for addition, preventing a direct route to access a potentially valuable class of oxygen-containing organoboron reagents for divergent synthesis. We herein report the realization of an alkoxyboration reaction, the addition of boron-oxygen σ bonds to alkynes. Functionalized O-heterocyclic boronic acid derivatives are produced using this transformation, which is mild and exhibits broad functional group compatibility. Our results demonstrate activation of this boron-O σ bond using a gold catalysis strategy that is fundamentally different from that used previously for other boron addition reactions.
- Hirner, Joshua J.,Faizi, Darius J.,Blum, Suzanne A.
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supporting information
p. 4740 - 4745
(2014/04/17)
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- Catalytic C-H activation of phenylethylamines or benzylamines and their annulation with allenes
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Tetrahydro-3-benzazepines and tetrahydroisoquinolines are synthesized in one step from allenes and phenylethylamines or benzylamines, respectively. Mechanistically, it is assumed that activation of a C-H bond of an aromatic ring with Pd(II) occurs, directed by the primary amine, leading to the formation of a palladacycle into which an allene then undergoes insertion. The resulting π-allyl intermediate cyclizes to the products by an intramolecular allylic alkylation. The process is particularly useful with 2,3-butadienoates and amines having a quaternary carbon at the α-position. (Chemical Equation Presented).
- Rodrguez, Aleix,Albert, Joan,Ariza, Xavier,Garcia, Jordi,Granell, Jaume,Farrs, Jaume,La Mela, Andrea,Nicols, Ernesto
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p. 9578 - 9585
(2015/02/19)
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- Synthesis of novel derivatives of murrayafoline a and their inhibitory effect on LPS-stimulated production of pro-inflammatory cytokines in bone marrow-derived dendritic cells
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A series of N-substituted-1,2,3-triazole murrayafoline A derivatives were successfully synthesized using click azide-alkyne Huisgen cycloaddition reaction between 1-methoxy-3-methyl-9-(3-azido)-propyl-9H-carbazole and substituted alkynes. Their chemical structures were confirmed by 1H, 13C NMR and HR-ESI-MS spectral data. In addition, the interested effects on LPS-stimulated production of pro-inflammatory cytokines in bone marrow-derived dendritic cells of synthetic murrayafoline A derivatives were also investigated. Our results indicated that murrayafoline A derivatives containing 1,2,3-triazole nucleus potentially possessed anti-inflammatory action through inhibiting production of IL-6, IL-12 p40 and TNF-α.
- Thuy, Tran Thi Thu,Cuong, Nguyen Manh,Toan, Tran Quoc,Thang, Ngo Ngoc,Tai, Bui Huu,Nhiem, Nguyen Xuan,Hong, Hye-Jin,Kim, Sohyun,Legoupy, Stephanie,Koh, Young Sang,Kim, Young Ho
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p. 832 - 839
(2013/07/26)
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- Unprecedented biological cyclopropanation in the biosynthesis of FR-900848
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We were able to show the predominant incorporation of a single enantiomer and intact incorporation of multiply labelled synthetic diketide precursors (14 and 16), which established the intermediacy of cyclopropanated diketide and led to our proposal for t
- Tokiwano, Tetsuo,Watanabe, Hiroaki,Seo, Takashi,Oikawa, Hideaki
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scheme or table
p. 6016 - 6018
(2009/05/06)
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- Highly convergent three component benzyne coupling: The total synthesis of ent-clavilactone B
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The first total synthesis of (+)-clavilactone B, a potent antifungal agent and novel tyrosine kinase inhibitor, is described. The absolute configuration of clavilactones has been unambiguously established by using Sharpless asymmetric epoxidation to gener
- Larrosa, Igor,Da Silva, Marianne I.,Gomez, Patricio M.,Hannen, Peter,Ko, Eunjung,Lenger, Steven R.,Linke, Simon R.,White, Andrew J. P.,Wilton, Donna,Barrett, Anthony G. M.
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p. 14042 - 14043
(2007/10/03)
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- Stille reactions catalytic in tin: A "Sn-F" route for intermolecular and intramolecular couplings
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(Chemical Equation Presented) Polymethylhydrosiloxane (PMHS) made hypercoordinate by KF(aq) allows Me3SnH to be recycled during a Pd(0)-catalyzed hydrostannation/Stille cascade. Starting with a variety of alkynes, in situ vinyltin formation is followed by Stille reaction with aryl, styryl, benzyl, or vinyl electrophiles present in the reaction mixture. Both inter- and intramolecular versions of the process are possible with tin loads of approximately 6 mol %. Regeneration of the organotin hydride is believed to proceed through a Me3SnF intermediate. Given the aggregated nature of organotin fluorides and the ability to use these organotins in substoichiometric quantities, the hazards and purification problems associated with the removal of organotin wastes from reaction mixtures are minimized.
- Gallagher, William P.,Maleczka Jr., Robert E.
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p. 841 - 846
(2007/10/03)
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- A stereodivergent approach to amino acids, amino alcohols, or oxazolidinones of high enantiomeric purity
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(-)-Menthone, an inexpensive chiral auxiliary, was used to prepare both enantiomers of α-amino acids, amino alcohols, or oxazolidinones. The sequence includes the SN2′ displacement by a cuprate reagent and a Curtius rearrangement as key steps.
- Spino, Claude,Tremblay, Marie-Claude,Gobdout, Cedrickx
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p. 2801 - 2804
(2007/10/03)
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- Synthesis and Cycloaromatization of a Cyclic Enyne-Allene Prodrug
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A simple and stable cyclic enediynone (4) has been synthesized using an intramolecular Nozaki-Hiyama-Kishi cyclization as the key step. Reaction with a thiolate nucleophile led to rapid cycloaromatization of 4. Trapping experiments using 1,4-cyclohexadien
- Bekele, Tefsit,Brunette, Steven R.,Lipton, Mark A.
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p. 8471 - 8479
(2007/10/03)
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- Stille couplings catalytic in tin: a "Sn-F" approach.
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A new tin recycling method for Stille couplings catalytic in tin is reported. PMHS made hypercoordinate by KF((aq)) allows Me(3)SnH to be efficiently recycled during a Pd(0)-catalyzed hydrostannation/Stille cascade. Relative to previously disclosed protoc
- Maleczka Jr.,Gallagher
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p. 4173 - 4176
(2007/10/03)
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- Effect of amines on the selective bromination of some β-substituted-2- butenoic esters
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The effect of amines on the selective bromination of some β- substituted-2-butenoic esters is described. The bromination of methyl (Z)4-t- butyldiphenylsilyloxy-3-methylbutenoate 2 in the presence of DIPEA (N, N- diisopropylethylamine) and the successive
- Nakada, Masahisa,Kojima, Ei-Ichi,Ichinose, Hidehiro
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p. 863 - 868
(2007/10/03)
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- α,β-Unsaturated acyl silanes
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A rapid method for the synthesis of αβ-unsaturated acyl silanes from allenyl trialkylsilyl ethers and aldehydes or ketones has been developed. The method is general and leads to the acyl silane products in good to excellent yields.
- Stergiades, Ioanna A.,Tius, Marcus A.
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p. 7547 - 7551
(2007/10/03)
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- Axial chiral liquid crystals - Synthesis of trisubstituted allenyl ethers
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The synthesis of racemic and enantiomerical enriched axial chiral liquid crystalline compounds incorporating a trisubstituted allene unit is described. All compounds 16-28 display the smectic C-phase and mostly also a nematic mesophase. All investigated e
- Lunkwitz, Ralph,Zab, Kerstin,Tschierske, Carsten
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scheme or table
p. 662 - 668
(2011/10/11)
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- Stereoselective total synthesis of the pseudopterolide kallolide A
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A total synthesis of the pseudopterolides, kallolide A (36) and kallolide A acetate (35), has been achieved. The racemic forms were prepared from the syn adduct 20 of furan 13 and stannane 17 (BF3·OEt2-promoted addition) via the 15-membered propargylic allylic ether 25. [2,3]Wittig ring contraction led to the cis, anti, cis product 26. Alcohol 26 was transformed to butenolide 34 with net retention of configuration by Pd(PPh3)4- catalyzed carbonylation of the mesylate 27 and ensuing AgNO3-catalyzed cyclization of the derived allenic acid 29. Solvolysis of the SEM ether (at C2) 34 in acetic acid or aqueous t-BuOH afforded racemic kallolide A acetate (35) and kallolide A (36), respectively, with inversion of stereochemistry by an S(N)1 process. Key elements of stereocontrol, including the steric outcome of the [2,3]Wittig ring contraction, the allenic ester isomerization, and the solvolysis reactions, were predicted from molecular mechanics calculations. The C8 and C2 epimers 45 and 46 of the cis, anti, cis kallolide A SEM ether precursor 34 were also prepared. The synthetic route originated from the anti adduct 19 of aldehyde 13 and the allylic chloride 16 and CuCl (cat), HSiCl3, and i-Pr2NEt. Adduct 19 was subjected to the same sequence as the syn counterpart 20 to produce the trans, anti, cis[2,3]Wittig ring contraction product 42. The derived alleonate 44 afforded a 1:1 mixture of butenolides 45 and 46 upon sequential treatment with TBAF and AgNO3. Finally, the natural enantiomer (+)-36 of kallolide A was synthesized from the enantioenriched syn adduct (+)-20, prepared by addition of allylic stannane 17 to aldehyde 13 promoted by a modified chiral acyloxyborane Lewis acid.
- Marshall, James A.,Liao, Junkai
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p. 5962 - 5970
(2007/10/03)
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- Molecular design, chemical synthesis, and study of novel enediyne-sulfide systems related to the neocarzinostatin chromophore
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The design and synthesis of the novel monocyclic enediyne-sulfide systems and their chemical and DNA cleavage properties are described. The parent enediyne-sulfide 6 possessing a hydroxy group at the allylic position was effectively synthesized via the cr
- Toshima, Kazunobu,Ohta, Kazumi,Ohashi, Aya,Nakamura, Takatsugu,Nakata, Masaya,Tatsuta, Kuniaki,Matsumura, Shuichi
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p. 4822 - 4831
(2007/10/02)
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- Synthesis of Novel Fused β-Lactams by Intramolecular 1,3-Dipolar Cycloadditions. Part 9. Preparation of the 7-Oxo-1,3-dizabicycloheptane-2-carboxylate and 8-Oxo-1,3-dizabicyclooctane-2-carboxylate Ring Systems
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4-Vinylazetidin-2-one (24) has been converted into 1--4-vinylazetidin-2-one (27) and 1--4-(2-methoxycarbonylvinyl)-azetidin-2-one (43) which on thermolysis in toluene gave (2RS,5RS)-ben
- Branch, Clive L.,Pearson, Michael J
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p. 1077 - 1096
(2007/10/02)
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