- Site-Selective trans-Hydrostannation of 1,3- and 1,n-Diynes: Application to the Total Synthesis of Typhonosides E and F, and a Fluorinated Cerebroside Analogue
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Propargyl alcohols are privileged substrates for stereochemically unorthodox trans-hydrostannation reactions catalyzed by [Cp*RuCl]4 (Cp=pentamethylcyclopentadienyl), because an incipient hydrogen bond between the -OH group and the polarized [Ru-Cl] unit assists substrate binding. For this very reason, it is also possible to subject diyne derivatives carrying one -OH group to site-selective stannylation, even if the acetylene units are conjugated and hence, electronically coupled. An unusual temperature dependence was observed in that heating tends to improve site-selectivity, whereas per-stannylation is favored when the reaction is carried out in the cold. This counterintuitive trend can be rationalized based on spectroscopic data; additional support comes from the isolation of the unusual bimetallic complex 11. The bridging fulvene and enynyl ligands in 11 are thought to reflect an interligand redox isomerization process likely triggered by synchronous activation of the 1,3-diyne substrate by two metal centers. The preparative relevance of site-selective trans-hydrostannation is illustrated by the total synthesis of two members of the typhonoside series of glycolipids, which are endowed with neuroprotective properties. Moreover, the preparation of a fluoroalkene sphingosine analogue shows that the tin residue also serves as a versatile handle for late-stage modification of a bioactive target compound.
- Mo, Xiaobin,Letort, Aurélien,Ro?ca, Drago?-Adrian,Higashida, Kosuke,Fürstner, Alois
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- Synthesis of enantiopure aliphatic acetylene alcohols and determination of their absolute configurations by 1H NMR anisotropy and/or X-ray crystallography
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The MαNP acid method has been applied to racemic aliphatic acetylene alcohols in order to simultaneously prepare enantiopure alcohols and to determine their absolute configurations by 1H NMR anisotropy. Racemic acetylene alcohols 6-8, 11, and 20 were esterified with MαNP acid (S)-(+)-1 to yield diastereomericMαNP esters which were efficiently separated by HPLC on silica gel with separation factors α in the range 1.60-1.93. The 1H NMR anisotropy factors Δδ [= δ(2nd fr.) - δ(1st fr.)] were calculated from the data of the first- (22a-27a) and second-eluted MαNP esters (22b-27b). The absolute configurations of the first-eluted esters were determined from the distribution of Δδ values in the MαNP sector rule. In the case of MαNP ester 26b, the assigned absolute configuration was confirmed by X-ray crystallography. The solvolysis of MαNP esters yielded enantiopure acetylene alcohols 5-8 with established absolute configurations. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Sekiguchi, Satoshi,Akagi, Megumi,Naito, Junpei,Yamamoto, Yoko,Taji, Hiromi,Kuwahara, Shunsuke,Watanabe, Masataka,Ozawa, Yoshiki,Toriumi, Koshiro,Harada, Nobuyuki
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- Lipidic synthetic alkaloids as SK3 channel modulators. Synthesis and biological evaluation of 2-substituted tetrahydropyridine derivatives with potential anti-metastatic activity
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Small Conductance Calcium (Ca2+)-activated potassium (K+) channels (SKCa) are now proved to be involved in many cancer cell behaviors such as proliferation or migration. The SK3 channel isoform was particularly described in breast cancer where it can be associated with the Orai1 Ca2+ channel to form a complex that regulates the Ca2+ homeostasis during tumor development and acts as a potent mediator of bone metastases development in vivo. Until now, very few specific blockers of Orai1 and/or SK3 have been developed as potential anti-metastatic compounds. In this study, we illustrated the synthesis of new families of lipophilic pyridine and tetrahydropyridine derivatives designed as potential modulators of SK3 channel. The toxicity of the newly synthesized compounds and their migration effects were evaluated on the breast cancer cell line MDA-MB-435s. Two molecules (7a and 10c) demonstrated a significant decrease in the SK3 channel-dependent migration as well as the SK3/Orai1-related Ca2+ entry. Current measurements showed that these compounds are more likely SK3-selective. Taken all together these results suggest that such molecules could be considered as promising anti-metastatic drugs in breast cancer.
- Braire, Julien,Chant?me, Aurélie,Dubreuil, Didier,Félix, Romain,Jaffrès, Paul-Alain,Kouba, Sana,Lebreton, Jacques,Mathé-Allainmat, Monique,Pipelier, Muriel,Potier-Cartereau, Marie,Trebak, Mohamed,Vandier, Christophe,Zhang, Xuexin
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- Discovery of Anti-TNBC Agents Targeting PTP1B: Total Synthesis, Structure-Activity Relationship, in Vitro and in Vivo Investigations of Jamunones
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Twenty-three natural jamunone analogues along with a series of jamunone-based derivatives were synthesized and evaluated for their inhibitory effects against breast cancer (BC) MDA-MB-231 and MCF-7 cells. The preliminary structure-activity relationship revealed that the length of aliphatic side chain and free phenolic hydroxyl group at the scaffold played a vital role in anti-BC activities and the methyl group on chromanone affected the selectivity of molecules against MDA-MB-231 and MCF-7 cells. Among them, jamunone M (JM) was screened as the most effective anti-triple-negative breast cancer (anti-TNBC) candidate with a high selectivity against BC cells over normal human cells. Mechanistic investigations indicated that JM could induce mitochondria-mediated apoptosis and cause G0/G1 phase arrest in BC cells. Furthermore, JM significantly restrained tumor growth in MDA-MB-231 xenograft mice without apparent toxicity. Interestingly, JM could downregulate phosphatidylinositide 3-kinase (PI3K)/Akt pathway by suppressing protein-tyrosine phosphatase 1B (PTP1B) expression. These findings revealed the potential of JM as an appealing therapeutic drug candidate for TNBC.
- Hu, Caijuan,Li, Guoxun,Mu, Yu,Wu, Wenxi,Cao, Bixuan,Wang, Zixuan,Yu, Hainan,Guan, Peipei,Han, Li,Li, Liya,Huang, Xueshi
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supporting information
p. 6008 - 6020
(2021/05/06)
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- Rhodium-Catalyzed Remote C(sp3)?H Borylation of Silyl Enol Ethers
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A rhodium-catalyzed remote C(sp3)?H borylation of silyl enol ethers (SEEs, E/Z mixtures) by alkene isomerization and hydroboration is reported. The reaction exhibits mild reaction conditions and excellent functional-group tolerance. This method is compatible with an array of SEEs, including linear and branched SEEs derived from aldehydes and ketones, and provides direct access to a broad range of structurally diverse 1,n-borylethers in excellent regioselectivities and good yields. These compounds are precursors to various valuable chemicals, such as 1,n-diols and aminoalcohols.
- Li, Jie,Qu, Shuanglin,Zhao, Wanxiang
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supporting information
p. 2360 - 2364
(2020/01/02)
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- Acridine Photocatalysis: Insights into the Mechanism and Development of a Dual-Catalytic Direct Decarboxylative Conjugate Addition
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Conjugate addition is one of the most synthetically useful carbon-carbon bond-forming reactions; however, reactive carbon nucleophiles are typically required to effect the addition. Radical conjugate addition provides an avenue for replacing reactive nucleophiles with convenient radical precursors. Carboxylic acids can serve as simple and stable radical precursors by way of decarboxylation, but activation to reactive esters is typically necessary to facilitate the challenging decarboxylation. Here, we report a direct, dual-catalytic decarboxylative radical conjugate addition of a wide range of carboxylic acids that does not require acid preactivation and is enabled by the visible light-driven acridine photocatalysis interfaced with an efficient copper catalytic cycle. Mechanistic and computational studies provide insights into the roles of the ligands and metal species in the dual-catalytic process and the photocatalytic activity of substituted acridines.
- Arman, Hadi D.,Dang, Hang T.,Haug, Graham C.,Larionov, Oleg V.,Nguyen, Viet D.,Nguyen, Vu T.,Vuong, Ngan T. H.
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p. 11448 - 11457
(2020/11/17)
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- Novel Process for the Synthesis of Docosanol
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The present invention relates to a novel process for the preparation of Docosanol (I). More particularly, the invention relates to a novel process for the preparation of Docosanol (I) in a substantially pure form with a purity level of greater than 99.5%. The invention also relates to novel crystalline forms of Docosanol (I) and process for preparation thereof.
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Paragraph 0109; 0110
(2019/06/15)
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- Unexpected AChE inhibitory activity of (2E)α,β-unsaturated fatty acids
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A small library of (E) α,β-unsaturated fatty acids was prepared, and 20 different saturated and mono-unsaturated fatty acids differing in chain length were subjected to Ellman's assays to determine their ability to act as inhibitors for AChE or BChE. While the compounds were only very weak inhibitors of BChE, seven molecules were inhibitors of AChE holding IC50 = 4.3–12.8 M with three of them as significant inhibitors of this enzyme. The results have shown trans 2-mono-unsaturated fatty acids are better inhibitors for AChE than their saturated analogs. Furthermore, the screening results indicate that the chain length is crucial for obtaining an inhibitory efficacy. The best results were obtained for (2E) eicosenoic acid (14) showing inhibition constants Ki = 1.51 ± 0.09 M and Ki′ = 7.15 ± 0.55 M. All tested compounds were mixed-type inhibitors with a dominating competitive part. Molecular modelling calculations indicate a different binding mode of active/inactive compounds for the enzymes AChE and BChE.
- Loesche, Anne,Wiemann, Jana,Al Halabi, Zayan,Karasch, Julia,Sippl, Wolfgang,Csuk, René
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p. 3315 - 3319
(2018/09/17)
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- Trans-2-nonadecyl-4-hydroxymethyl-1,3-dioxolane and method for producing thereof
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The present invention discloses a method for producing trans-2-nonadecyl-4-hydroxymethyl-1,3-dioxolane comprising mixing alkanes and pyridinium chlorochromat for an oxidation reaction; obtaining a product by the oxidation reaction for processing an aldolization reaction and then purifying for obtaining a trans-2-nonadecyl-4-hydroxymethyl-1,3-dioxolane compound. According to the method of the present invention, it is able to promote the productivity and reduce the cost.
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Paragraph 0014-0016
(2015/07/27)
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- TRANS-2-NONADECYL-4-HYDROXYMETHYL-1，3-DIOXOLANE AND METHOD FOR PRODUCING THEREOF
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The present invention relates to a method for preparing a compound and, more specifically, to a method for preparing trans-2-nonadecyl-4-hydroxymethyl-1,3-dioxolane, which comprises the steps of: carrying out an oxidation reaction of an alcohol and pyridinium chlorochromate; proceeding with acetylation of the obtained compound resulting from the oxidation reaction; and purifying the acetylated compound to obtain trans-2-nonadecyl-4-hydroxymethyl-1,3-dioxolane. The preparation method can remarkably improve the compound yield and save production costs.COPYRIGHT KIPO 2015
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Paragraph 0023-0025
(2017/01/02)
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- The synthesis of long-chain α-alkyl-β-hydroxy esters using allylic halides in a Frater-Seebach alkylation
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The Frater-Seebach alkylation is a highly efficient means to diastereoselectively introduce α-substituents to chiral β-hydroxy esters, however, the yields of reactions in which longer chain alkyl halides are used can be disappointing. To provide a more robust protocol for the alkylation of β-hydroxy esters, we prepared a variety of long-chain allylic iodides with the view that the greater reactivity of the allylic system would lead to enhanced efficiency. Indeed, for all substrates studied, the yield of the α-alkylation was greatly improved for the unsaturated allylic halides compared to their analogous saturated counterparts. Our methodology thus provides an improved means by which to access a variety of important lipophilic compounds such as mycolic acids, which are found on the cell wall of M. tuberculosis. An improved methodology for the introduction of α-substituents to chiral β-hydroxy esters using Frater-Seebach methodology is presented. Long-chain allylic iodides resulted in better yields for the α-alkylation compared to their saturated counterparts. This methodology provides an improved means by which to access a variety of important lipophilic compounds such as mycolic acids. Copyright
- Khan, Ashna A.,Chee, Stephanie H.,Stocker, Bridget L.,Timmer, Mattie S. M.
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supporting information; experimental part
p. 995 - 1002
(2012/03/27)
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- A first total synthesis of ganglioside HLG-2
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A first synthesis of the neuri-tegenic ganglioside HLG-2, which was identified in extracts of the sea cucumber Holothuria leucospilota, is described. The characteristic sequence of the trisaccharide part, α-N-glycolylsial-yl-(2,4)-& α-N-acetylsialyl-(2,6)-glucoside, was efficiently assembled by coupling of a highly active N-2,2,2-trichloro- ethoxycarbonyl (Troc)-protected sialyl donor and a 1,5-lactamized sialyl ac- ceptor with high stereoselectivity. The corresponding trisaccharyl imidate donor was directly glycosidated with the primary hydroxyl group of the ceramide part, producing protected HLG-2 in relatively high yield, global deprotection of which furnished ganglioside HLG-2 in highly pure form.
- Iwayama, Yuki,Ando, Hiromune,Ishida, Hideharu,Kiso, Makoto
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experimental part
p. 4637 - 4648
(2010/03/01)
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- Semivolatile and volatile compounds in combustion of polyethylene
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The evolution of semivolatile and volatile compounds in the combustion of polyethylene (PE) was studied at different operating conditions in a horizontal quartz reactor. Four combustion runs at 500 and 850°C with two different sample mass/air flow ratios and two pyrolytic runs at the same temperatures were carried out. Thermal behavior of different compounds was analyzed and the data obtained were compared with those of literature. It was observed that α,ω-olefins, α-olefins and n-paraffins were formed from the pyrolytic decomposition at low temperatures. On the other hand, oxygenated compounds such as aldehydes were also formed in the presence of oxygen. High yields were obtained of carbon oxides and light hydrocarbons, too. At high temperatures, the formation of polycyclic aromatic hydrocarbons (PAHs) took place. These compounds are harmful and their presence in the combustion processes is related with the evolution of pyrolytic puffs inside the combustion chamber with a poor mixture of semivolatile compounds evolved with oxygen. Altogether, the yields of more than 200 compounds were determined. The collection of the semivolatile compounds was carried out with XAD-2 adsorbent and were analyzed by GC-MS, whereas volatile compounds and gases were collected in a Tedlar bag and analyzed by GC with thermal conductivity and flame ionization detectors.
- Font, Rafael,Aracil, Ignacio,Fullana, Andrés,Conesa, Juan A.
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p. 615 - 627
(2007/10/03)
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- Anchor dependency for non-glycerol based cationic lipofectins: Mixed bag of regular and anomalous transfection profiles
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Although detailed structure-activity, physicochemical and biophysical investigations in probing the anchor influence in liposomal gene delivery have been reported for glycerol-based transfection lipids, the corresponding investigation for non-glycerol based simple monocationic transfection lipids have not yet been undertaken. Towards this end, herein, we delineate our structure-activity and physicochemical approach in deciphering the anchor dependency in liposomal gene delivery using fifteen new structural analogues (lipids 1-15) of recently reported non-glycerol based monocationic transfection lipids. The C14 analogues in both series 1 (lipids 1-6) and series 2 (lipids 7-15) showed maximum efficiency in transfecting COS-1 and CHO cells. However, the C12 analogue of the ether series (lipid 3) exhibited a seemingly anomalous behavior compared with its transfection efficient C10 and C14 analogues (lipids 2 and 4) in being completely inefficient to transfect both COS-1 and CHO cells. The present structure-activity investigation also convincingly demonstrates that enhancement of transfection efficiencies through incorporation of membrane re-organizing unsaturation elements in the hydrophobic anchor of cationic lipids is not universal but cell dependent. The strength of the interaction of lipids 1-15 with DNA was assessed by their ability to exclude ethidium bromide bound to the DNA. Cationic lipids with long hydrophobic tails were found, in general, to be efficient in excluding EtBr from DNA. Gel to liquid crystalline transition temperatures of the lipids was measured by fluorescence anisotropy measurement technique. In general (lipid 2 being an exception), transfection efficient lipids were found to have their mid transition temperatures at or below physiological temperatures (37°C).
- Singh, Rajkumar Sunil,Mukherjee, Koushik,Banerjee, Rajkumar,Chaudhuri, Arabinda,Hait, Samik Kumar,Moulik, Satya Priya,Ramadas, Yerramsetti,Vijayalakshmi, Amash,Rao, Nalam Madhusudhana
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p. 900 - 909
(2007/10/03)
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- Preparation of functionalized dialkylzincs via a boron-zinc exchange. Reactivity and catalytic asymmetric addition to aldehydes
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The hydroboration of olefins with Et2BH provides diethyl(alkyl)boranes 2 which readily undergo a boron - zinc exchange with Et2Zn providing a range of polyfunctional primary, secondary, and benzylic diorganozincs. The resulting diorganozincs 3 have been reacted with various electrophiles (allylic halides, acid chlorides, alkylidenemalonates, ethyl propiolate, nitroolefins) in the presence of CuCN·2LiCl with excellent yields. With secondary dialkylzincs prepared from diastereomerically pure diethyl(alkyl)boranes, the boron-zinc exchange occurs with loss of stereochemistry. The asymmetric addition of 3 to aldehydes in the presence of the chiral catalyst 55 furnishes optically active polyfunctional secondary alcohols (50 to over 96% ee).
- Langer, Falk,Schwink, Lothar,Devasagayaraj, Arokiasamy,Chavant, Pierre-Yves,Knochel, Paul
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p. 8229 - 8243
(2007/10/03)
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- Homologous long-chain alkanediols from Papaver leaf cuticular waxes
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In cuticular waxes from leaves of Papaver alpinum sensu Markgr., P. dubium L., P. nudicaule L., P. orientale L., P. rhoeas L. and P. somniferum L., six new alkanediols carrying one primary and one secondary hydroxyl function were identified. Five of them, docosane-1,3-diol, hexacosane-1,7- diol, octacosane-1,9-diol, nonacosane-1,10-diol and triacontane-1,11-diol, form a homologous series. Their molecular geometries and relative proportions suggest a biosynthetic relationship to the corresponding primary alkanols.
- Jetter, Reinhard,Riederer, Markus,Seyer, Andre,Mioskowski, Charles
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p. 1617 - 1620
(2007/10/03)
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- Studies on PPL catalyzed acetylation of 2-alkanols: Its application for the synthesis of 2-dodecanol and 2-tridecyl acetate, the pheromones of Crematogaster ants and Drosophila mulleri flies
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Several aliphatic 2-alkanols with varying chain length has been efficiently resolved by their acetylation using vinyl acetate/PPL in diisopropyl ether. The effect of solvent polarity, position and type of unsaturation and chain length has been probed. This has led to more convenient synthesis of some insect pheromones.
- Sharma, Anubha,Pawar, Archana S.,Chattopadhyay, Subrata
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- Catalytic Asymmetric Reductive Addition of Olefins to Aldehydes Mediated by Boron and Zinc Organometallics
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A procedure involving a hydroboration, boron-zinc exchange and asymmetric addition to an aldehyde allows the reductive addition of olefins to aldehydes in 50-96percent ee.A short and efficient 3 step synthesis of ginnol (61percent overall yield, 92percent ee) demonstrates the synthetic utility of the method.
- Schwink, Lothar,Knochel, Paul
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p. 9007 - 9010
(2007/10/02)
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- AN IMPROVED DIRECT OXIDATION OF ALKYL HALIDES TO ALDEHYDES
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The oxidation of alkyl chlorides and bromides with dimethyl sulfoxide has been performed in the presence of sodium iodide.This method allows a convenient one-step procedure for the preparation of aldehydes from alkyl chlorides and bromides.
- Dave, Paritosh,Byun, Hoe-Sup,Engel, Robert
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p. 1343 - 1346
(2007/10/02)
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- Application of the Rosenmund reaction to the synthesis of saturated fatty aldehydes.
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A method is described for the simple and rapid formation of saturated fatty aldehydes from the corresponding acid chlorides. It is not suitable for the preparation of unsaturated aldehydes because of the partial reduction and positional and geometrical isomerization of the double bond in the chain.
- White Jr.,Sulya,Cain
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p. 158 - 160
(2007/10/10)
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