- Enantioselective aldol-type reaction using diketene
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An aldol-type reaction catalyzed by a Ti-(S)-BINOL complex using with a diketene as substrate is described herein. The complex derived from 1.0 molar equivalent of Ti(O-i-Pr)4 and 2.0 molar equivalents of (S)-BINOL gave (5)-isopropyl 5-hydroxy-7-phenyl-3-oxo-6-heptenoate with high enantioselectivity.
- Kawase, Takahiro,Takizawa, Shinobu,Jayaprakash, Doss,Sasai, Hiroaki
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Read Online
- Br?nsted acidic cellulose-PO3H: An efficient catalyst for the chemoselective synthesis of fructones and trans-esterification via condensation of acetoacetic esters with alcohols and diols
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Cellulose is the most abundant organic source and has expedient a great deal of interest as renewable and emerged as sustainable feedstock. The functionalization of cellulose as designed catalytic system intriguing furnished to the production of fine chemicals. Herein, we synthesized an environmental friendly solid acid catalyst by functionalizing cellulose with phosphoric acid (PO3H). The successful functionalization of cellulose with PO3H was confirmed by 31P NMR, ICP-OES, FE-SEM, and XPS analysis. ICP-OES revealed the presence of phosphorus content of ～1.0 wt. % on the catalyst's surface while elemental mapping by FESEM and XPS shows a uniform distribution of phosphorus over the material. The synthesized solid acid catalyst was utilized for condensation of diols with acetoacetic esters in solvent-free conditions to synthesize fine chemicals. The present approach not only circumvented the one-step protection and other products but more fascinatingly provided trans-esterification of acetoacetic esters with diols and n-alcohols. The catalyst was successfully used for chemoselective protection on ethyl acetoacetate with 1, 2 diols to essential fructone molecule with ～100% conversion and 99% selectivity. The results suggested that the catalyst has the advantage over commercial solid acid heterogeneous and homogeneous catalysts.
- Naikwadi, Dhanaji R.,Singh, Amravati S.,Biradar, Ankush V.
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- Revisiting ageless antiques; synthesis, biological evaluation, docking simulation and mechanistic insights of 1,4-Dihydropyridines as anticancer agents
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The historic DHP nucleus was serendipitously discovered by Arthur Hantzsch about 130 years ago and is still considered a hidden treasure for various pharmacological activities. Twenty-one DHP analogues were synthesized using the expedient one pot Hantzsch synthesis for screening as anticancer agents. Initially, the in vitro anti-proliferative single dose against a panel of 18 cancer cell lines showed that compounds 11b and 8f were the superlative candidates regarding their antitumor effect (GI% mean = 66.40% and 50.42%, correspondingly) compared to cisplatin (GI% mean = 65.58%) and doxorubicin (GI% mean = 74.56%). Remarkably, compound 11b showed a remarkable MDA-MB-468 anticancer activity (GI%=80.81%), higher than cisplatin (64.44%) and doxorubicin (76.72%), as well as strong antitumor activity against lung cancer A549 (GI%= 83.02%), more powerful than both cisplatin and doxorubicin. Compound 11b exhibited an exceptional anticancer activity against lung cancer cell line (A549) as its GI50 in nanomolar was (540 nM) with a 9-fold increase greater than cisplatin (GI50 = 4.93 μM) and with a selectivity index = 131 to cancer cells over normal cells. Further mechanistic investigations proved that DHPs anticipate simultaneously TOPI and RTKs (VEGFR-2, HER-2 and BTK) which can stimulate BAX/BAK and the executioner caspases via rtPCR studies.
- Sidhom, Peter A.,El-Bastawissy, Eman,Salama, Abeer A.,El-Moselhy, Tarek F.
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supporting information
(2021/06/21)
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- N, N’-dimethyl formamide (DMF) mediated Vilsmeier–Haack adducts with 1,3,5-triazine compounds as efficient catalysts for the transesterification of β-ketoesters
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N, N’-dimethyl formamide (DMF) mediated Vilsmeier–Haack (VH) adducts with 1,3,5-triazine compunds such as trichloroisocyanuric acid (TCCA) and trichlorotriazine (TCTA) were prepared by replacing classical oxy chlorides POCl3, and SOCl2, which were explored as efficient catalysts for the transesterification of β-ketoesters. The prepared (TCCA/DMF) and (TCTA/DMF) adducts improved greenery of the classical Vilsmeier–Haack reagents (POCl3/DMF), and (SOCl2/DMF), and demonstrated their better efficient catalytic ativity. Reaction times were in the range: 3.5 to 6.5 hr (SOCl2/DMF); 2.8–5.2 hr (POCl3/DMF); 2.5–5.2 hr (TCCA/DMF) and 2.5–5.0 hr (TCTA/DMF) catalytic systems. Ultrasonically (US) assisted protocols with these reagents further reduced the reaction times (two to three times), while microwave assisted (MW) protocols with these reagents were much more effective. The reactions could be completed in only few seconds (less than a minute) in MWassisted protocols as compared to US assited reactions, followed by good product yields.
- Chityala, Yadaiah,Duguta, Govardhan,Kamatala, Chinna Rajanna,Muddam, Bhooshan,Mukka, Satish Kumar
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supporting information
p. 1641 - 1655
(2020/05/25)
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- Nimodipine impurity IV reference substance as well as preparation method and application thereof
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The invention discloses a nimodipine impurity IV reference substance and a preparation method thereof. The method includes the steps that diketene, ethyl alcohol and triethylamine are taken and addedinto a container to be heated and cooled, reaction liquid is washed with water, washing liquid is discarded, anhydrous sodium sulfate is added and placed overnight, filtrate is obtained after filtration, ammonia gas is introduced into the filtrate until the filtrate is saturated, and the nimodipine impurity IV reference substance is obtained; and after the reaction is finished, m-nitrobenzaldehyde, methoxyethyl acetoacetate and ethanol are added, heating refulx is performed, the mixture is cooled and filtered, the solvent is removed through volatilization in a water bath to obtain a yellow viscous liquid, and recrystallization is carried out to obtain a yellow acicular crystal, namely the nimodipine impurity IV reference substance. The invention also discloses an application of the nimodipine impurity IV reference substance in nimodipine tablet consistency evaluation. According to the preparation method, the impurity IV can be prepared in a general analysis laboratory, special preparation equipment is not needed, the operation is simple, the purity of the obtained impurity reference substance can reach 98.4%, the purity requirement of the reference substance is met, and the preparation method can be used for consistency evaluation of the variety.
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Paragraph 0051-0052
(2020/11/22)
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- General [4 + 1] Cyclization Approach to Access 2,2-Disubstituted Tetrahydrofurans Enabled by Electrophilic Bifunctional Peroxides
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A general [4 + 1] cyclization reaction of carbonyl nucleophiles with 2-iodomethylallyl peroxides, which function as unique electrophilic oxygen synthons, for the synthesis of a broad range of 2,2-disubstituted tetrahydrofurans is achieved under operationally simple conditions. The unprecedented asymmetric version of such reaction is also realized via chiral auxiliary-assisted cyclization, thus providing a distinct approach to access chiral tetrahydrofurans with high diastereoselectivities. The new method can be applied to the synthesis of core structure of posaconazole drug.
- Gao, Min,Zhao, Yukun,Zhong, Chen,Liu, Shengshu,Liu, Pengkang,Yin, Qi,Hu, Lin
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supporting information
p. 5679 - 5684
(2019/08/01)
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- Design, synthesis, and bioactivity of dihydropyrimidine derivatives as kinesin spindle protein inhibitors
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A series of twenty-one 3,4-dihydropyrimidine derivatives bearing the heterocyclic 1,3-benzodioxole at position 4 in addition to different substituents at positions 2, 3 and 5 were designed and synthesized as monastrol analogs. The novel synthesized compounds were screened for their cytotoxic activity towards 60 cancer cell lines according to NCI (USA) protocol. Compounds 10b and 15 showed the best antitumor activity against most cell lines. Compound 15 was subsequently tested in 5-doses mode and displayed high selectivity towards CNS, prostate and leukemia subpanel with selectivity ratios of 22.30, 15.38 and 12.56, respectively at GI50 level. The IC50 of compounds 9d, 10b, 12, 15 and 16 against kinesin enzyme were 3.86 ± 0.12, 10.70 ± 0.35, 3.95 ± 0.12, 4.36 ± 0.14, and 14.07 ± 0.45 μM respectively, while the prototype compound, monastrol, reported IC50 value of 20 ± 0.42 μM. The safest compound among test compounds against normal cell line (HEK 293) is 10b with IC50 value of 62.02 ± 2.42 μM/ml in comparison to doxorubicin (IC50 = 11.34 ± 0.44 μM/ml). Cell cycle analysis of SNB-75 cells treated with compound 15 showed cell cycle arrest at G2/M phase. Further, the assay of levels of active caspase-3 and caspase-9 was investigated. Moreover, Molecular docking of compounds, 9d, 10b, 12, 15, 16, monastrol and mon-97 was performed to study the interaction between inhibitors and the kinesin spindle protein allosteric binding site.
- Tawfik, Haytham O.,El-Hamamsy, Mervat H.,Sharafeldin, Nabaweya A.,El-Moselhy, Tarek F.
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- Preparation technology of isopropyl acetoacetate
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The invention discloses a preparation technology of isopropyl acetoacetate. The preparation technology comprises the following steps: adding isopropanol and a catalyst into a reaction vessel, whereinthe catalyst is selected from aliphatic amine catalysts or tertiary amine catalysts; or the catalyst is prepared by mixing one or more of the aliphatic amine catalysts and the tertiary amine catalysts; raising the temperature to 20 to 100 DEG C, dropwise adding diketene, controlling the reaction temperature in the reaction process at 20 to 150 DEG C; after dropwise adding is finished, controllingthe temperature at 20 to 150 DEG C and carrying out thermal insulation for 0.5 to 6 hours, thus obtaining raw isopropyl acetoacetate, wherein the molar ratio of the isopropanol to the diketene is (1 to 1.8) to 1 and the adding amount of the catalyst is 0.1 to 1 weight percent of the total amount. By adopting a combined amine catalyst to carry out esterification reaction of the diketene and the isopropanol, the influence of steric hindrance of the isopropanol is reduced and the yield of esterification is improved; meanwhile, the difficulty of subsequent separation is reduced. After distillation, the yield of esterification liquid reaches 95 percent and the content of the esterification liquid reaches 99 percent or above.
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Paragraph 0038; 0039; 0040; 0042; 0044; 0046; 0048
(2018/05/03)
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- Prussian blue as an efficient catalyst for rate accelerations in the transesterification of β-ketoesters
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Prussian blue triggered transesterification of ethylacetoacetate with various alcohols underwent efficiently. The reaction is mild, eco-friendly, and selective with good yields. The proposed reaction pathway depicts the formation of an intermediate by the interaction of β-ketoesters with catalytic site of the Prussian blue, followed by nucleophilic attack of the alcohol at the electrophilic center followed by successive elimination of the proton to give the product. Observed longer reaction times under conventional conditions reduced amazingly under sonication and microwave irradiation followed enhanced yield of products.
- Srinivas,Rajanna,Krishnaiah,Kumar, M. Satish,Reddy, J. Narender
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p. 1212 - 1220
(2014/04/17)
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- AgOTf-catalyzed transesterification of β-keto esters
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AgOTf proved to be an effective catalyst for the transesterification of β-keto esters with primary, secondary and tertiary alcohols. The products were obtained in high yield within a reasonable reaction time period. The kinetics of the transesterification reaction were also studied and the reaction was found to follow second-order kinetics. Copyright
- Das, Rima,Chakraborty, Debashis
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experimental part
p. 140 - 144
(2012/05/20)
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- Design and synthesis of new 1,4-dihydropyridines containing 4(5)-chloro-5(4)-imidazolyl substituent as a novel calcium channel blocker
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New analogues of nifedipine, in which the ortho-nitro phenyl group at position 4 has been replaced by 4(5)-chloro-5(4)-imidazolyl substituent and which are able to interact with the receptor by hydrogen binding were designed, synthesized, and evaluated as calcium channel antagonists. The designed dihydropyridines were synthesized using the Hantzsch condensation and evaluated as calcium channel antagonists using the high K+ contraction of guineapig ileal longitudinal smooth muscle. A docking study was performed using the AutoDock4 program, and QSAR equations were obtained using multilinear regression. Our computational studies indicated that the oxygen of the ester (O10) and the N3′ of the imidazole ring form a hydrogen bonding interaction with the NH of HIS 363 and NH of LYS354, respectively, and that the sum of the BEHp5 and RDF075p are the most significant descriptors. The results of calcium channel antagonist evaluation demonstrated that increasing the chain length in C3 and C5 ester substituents increased activity. The most potent compound was the bis-phenylpropyl ester (5l) derivative, in that it was more active than the reference drug nifedipine and that the bis-phenylethyl ester (5k) derivative had comparable activity with nifedipine. The present research revealed that the 4(5)-chloro-5(4)-imidazolyl moiety is a bioisoster of o-nitrophenyl in nifedipine and provided novel dihydropyridines with more activity as calcium channel antagonists.
- Iman, Maryam,Davood, Asghar,Nematollahi, Ali Reza,Dehpoor, Ahmad Rerza,Shafiee, Abbas
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experimental part
p. 1417 - 1426
(2012/05/04)
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- Room temperature acylketene formation 1,3-dioxin-4-ones via silver(I) activation of phenylthioacetoacetate in the presence of ketones
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Silver(I) activation of thioacetoacetates in the presence of ketones produces 1,3-dioxin-4-ones. Mechanistic studies addressing the intermediacy of an acylketene intermediate are described.
- May, Aaron E.,Hoye, Thomas R.
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experimental part
p. 6054 - 6056
(2010/11/03)
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- Molecular iodine in ionic liquid: A green catalytic system for esterification and transesterification
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Esterification of carboxylic acids and transesterification of-ketoesters with alcohols have been developed using a catalytic amount of iodine in polyethylene glycol (PEG) ionic liquid (IL 1000) to afford the corresponding esters in good yields. By simple separation of the ionic-liquid phase containing the iodine, the system of I2/IL 1000 can be reused several times. Copyright
- Ren, Yiming,Cai, Chun
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scheme or table
p. 1670 - 1676
(2010/08/03)
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- Mild and high-yielding synthesis of β-keto esters and β-ketoamides
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In the presence of sodium acetate, the reaction between 2,2,6-trimethyl-4H-1,3-dioxin-4-one and secondary or tertiary alcohols (including chiral ones) or primary or secondary amines could be carried out in refluxing tetrahydrofuran, under much milder conditions than those described in the literature. In these new conditions, side products normally observed using the traditional protocol were avoided, and-keto esters and-ketoamides were normally obtained in quantitative yields.
- Sridharan, Vellaisamy,Ruiz, Miriam,Menendez, J. Carlos
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experimental part
p. 1053 - 1057
(2010/06/16)
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- BF3OEt2: An efficient catalyst for transesterification of β-ketoesters
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A facile and selective transesterification of β-ketoesters using BF3OEt2 as catalyst is described. The emphasis has been placed on the reaction of methyl acetoacetate with a series of alcohols of different structures, leading in all cases to good to excellent yields.
- Yang, Jinhui,Ji, Congbin,Zhao, Yanmin,Li, Yunfeng,Jiang, Shizhi,Zhang, Zhiwei,Ji, Yongqiang,Liu, Wanyi
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experimental part
p. 957 - 963
(2010/06/12)
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- PROCESS FOR PRODUCING ORGANIC COMPOUND AND ORGANIC COMPOUND OBTAINED BY THE SAME
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Disclosed herein are a reaction method and a production method of an organic compound which are capable of achieving high reaction selectivity according to the purpose and a high production rate of a target substance. The methods include at least two fluids, wherein at least one kind of the fluids is a fluid containing at least one organic compound and at least one kind of the fluids other than the above fluid is a fluid containing at least one reactant in the form of a liquid or solution, and the respective fluids join together in a thin film fluid formed between processing surfaces arranged to be opposite to each other so as to be able to approach to and separate from each other, at least one of which rotates relative to the other, whereby an organic reaction is performed in the thin film fluid.
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Page/Page column 83
(2010/08/18)
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- Synthesis, study of 3D structures, and pharmacological activities of lipophilic nitroimidazolyl-1,4-dihydropyridines as calcium channel antagonist
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QSAR studies indicated that the potency of nifedipine analogues was dependent upon lipophilicity, an electronic term and separated terms for each position on the DHP ring. Changes in the substitution pattern at the C3, C4, and C5 positions of DHPs alter potency, tissue selectivity, and the conformation of the 1,4-DHP ring. In this project a group of alkyl ester analogues of new derivatives of nifedipine, in which the ortho-nitrophenyl group at position 4 is replaced by a 1-methyl-5-nitro-2-imidazolyl substituent, and the methyl group at position 6 is replaced by a phenyl substituent, were synthesized and evaluated as calcium channel antagonist using the high K+ contraction of guinea-pig ileal longitudinal smooth muscle. The results for asymmetrical esters showed that lengthening of the substituent in C3 ester substituent increased activity. When increasing of the length is accompanied by increasing the hindrance, the activity decreased. The results demonstrate that all compounds were more active or similar in effect to that of the reference drug nifedipine.
- Miri, Ramin,Javidnia, Katayoun,Sarkarzadeh, Hasti,Hemmateenejad, Bahram
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p. 4842 - 4849
(2007/10/03)
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- Niobium(V) oxide: A new and efficient catalyst for the transesterification of β-keto esters
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Niobium(V) oxide is an efficient catalyst for the transesterification of β-keto esters with several kinds of alcohols, leading to good conversions. Moderate to good isolated product yields have been obtained at faster rates than those recently reported for various catalysts.
- De Sairre, Mirela Inês,Bronze-Uhle, érika Soares,Donate, Paulo Marcos
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p. 2705 - 2708
(2007/10/03)
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- ACETOACETYLATION OF ALCOHOLS, THIOLS AND AMINES IN A MICROREACTOR
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The invention relates to a method for the production of β-ketocarboxylic acid derivatives of formula (I) or the salts thereof, where X = NR', O or S, R, R', R1-R4 independently = H, alkyl, alkenyl, aryl or heteroaryl, by reaction of a diketene of formula (II) with a compound comprising an active hydrogen of formula ROH, NHRR' or RSH, characterised in that the reaction is continuously carried out in a microreactor.
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- Method for preparing chiral diphosphines
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The invention concerns a method for preparing a compound of formula (1) wherein: A represents naphthyl or phenyl optionally substituted; and Ar1, Ar2independently represent a saturated or aromatic carbocyclic group, optionally substituted.
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- Microwave-assisted solution-phase synthesis of 1,4,5-trisubstituted pyrazoles
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A small parallel library of 1,4,5-trisubstituted pyrazoles was prepared in solution using a three-step procedure starting from Meldrum acid. The Meldrum acid was acylated with different acyl chlorides and the products opened with different alcohols and amines to give substituted β-keto esters and β-keto amines. Further reaction with N,N-dimethylformamide dimethylacetal and the final cyclisation were effectively carried out under microwave irradiation. Scavenger resins were employed exclusively in the first step, whereas use of microwaves allowed complete conversion of the starting materials in the other two steps. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Giacomelli, Giampaolo,Porcheddu, Andrea,Salaris, Margherita,Taddei, Maurizio
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p. 537 - 541
(2007/10/03)
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- Synthesis and evaluation of pharmacological activities of 3,5-dialkyl 1,4-dihydro-2,6-dimethyl-4-nitroimidazole-3,5-pyridine dicarboxylates
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New analogues of nifedipine, in which the 2-nitrophenyl group at position 4 is replaced by a 1 -methyl-5-nitro-2-imidazolyl substituent, were synthesized. The symmetrical dialkyl 1,4-dihydro-2,6-dimethyl-4-(1-methyl-5-nitro-2-imidazolyl)-3, 5-pyridinedicarboxylates were prepared by a classical Hantzsch condensation. The asymmetrical analogues were synthesized using a procedure reported by Iwanami that involved the condensation of alkylacetoacetate with methyl-, ethyl- or isopropyl-3-aminocrotonate and 1 -methyl-5-nitroimidazole-2-carboxaldehyde. Calcium channel antagonist activities were determined in vitro using a guinea pig ileum longitudinal smooth muscle (GPILSM) assay. Many compounds exhibited superior, or equipotent, calcium antagonist activity (IC50 = 10- 10 to 10-13 M range) relative to the reference drug nifedipine (IC50 = 1.09? 0.12 × 10-11 M). Antinociceptive effects of some compounds were evaluated by the mouse tail-flick assay in vivo. Results demonstrate that some of the compounds were active as an antinociceptive.
- Miri, Ramin,Javidnia,Kebriaie-Zadeh,Niknahad,Shaygani,Semnanian,Shafiee
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p. 422 - 428
(2007/10/03)
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- A Simple and Efficient Method for Transesterification of β-Ketoesters Catalysed by Iodine
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A facile transesterification of β-ketoesters using catalytic iodine is described.
- Chavan, Subhash P.,Kale, Ramesh R.,Shivasankar,Chandake, Sanjay I.,Benjamin, Swapnanjali B.
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p. 2695 - 2698
(2007/10/03)
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- Zinc mediated transesterification of β-ketoesters and coumarin synthesis
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The transesterification of ketoesters using zinc and iodine is described. The reaction has been done on a variety of alcohols and phenols. Alcohols furnish transesterified products whereas phenols gave 4-methylcoumarins. The method is highly promising compared with existing methods.
- Chavan, Subhash P,Shivasankar,Sivappa,Kale, Ramesh
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p. 8583 - 8586
(2007/10/03)
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- Asymmetric hydrogenation method of a ketonic compound and derivative
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The present invention relates to a process for the asymmetric hydrogenation of a ketonic compound and derivative. The invention relates to the use of optically active metal complexes as catalysts for the asymmetric hydrogenation of a ketonic compound and derivative. The process for the asymmetric hydrogenation of a ketonic compound and derivative is characterized in that the asymmetric hydrogenation of said compound is carried out in the presence of an effective amount of a metal complex comprising as ligand an optically active diphosphine corresponding to one of the following formulae: STR1
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- Asymmetric Mn(III)-based radical synthesis of functionalized 2,3-dihydrofurans
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The oxidative radical addition of alkyl acetoacetates to p-methoxycinnamoyl oxazolidinones promoted by Mn(III) has been studied. It only gives trans-disubstituted 2,3-dihydrofurans, with d.r. ranging from 2:1 to 9:1, depending on the substituent of the chiral auxiliary. After chromatographic separation of the two diastereomers, the oxazolidinone can be removed to afford enantiopure dihydrofuranyl esters in good overall yield. (C) 2000 Elsevier Science Ltd.
- Garzino,Meou,Brun
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p. 9803 - 9807
(2007/10/03)
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- Synthesis of optically active N-allyl amino compounds with defined trisubstituted double bonds
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Optically active acyclic N-allylamino compounds with defined configurated trisubstituted double bonds were generated via a three step sequence. The first crucial step was a two-carbon chain elongation of chiral α-aminoacid esters succeeding in a Claisen ester condensation with acetic acid ester enolates. The so formed β-ketoesters were subjected to a one pot procedure of an enol trifluoromethanesulfonate generation and a consecutive palladium catalysed cross-coupling: A Stille or a Sonogashira type reaction allowed to generate selectively the trisubstituted E-olefins.
- Boesche, Uwe,Nubbemeyer, Udo
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p. 6883 - 6904
(2007/10/03)
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- Asymmetric N-(3,3-diphenylpropyl)aminoalkyl esters of 4-aryl-2,6- dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acids with antihypertensive activity
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A series of asymmetric 4-aryl-1,4-dihydropyridine-3,5-dicarboxylates characterized by the presence of a 3,3-diphenylpropylamino moiety in one of the ester groups were synthesized. They exhibited remarkable antihypertensive activity in spontaneously hypertensive rats as well as affinity for the 1,4- dihydropyridines binding site labelled by 3H-nitrendipine in the calcium channel. Introduction of this bulky and lipophilic amine confers to the whole series an elevated level of antihypertensive activity and a long duration of action, a structure-dependent modulation of the activity being found only in the subset characterized by the presence of a branched propylene bridge between the ester and the amino groups. The presence of the amino group is essential for oral activity. Out of this series, compound 9u (Rec 15/2375- lercanidipine) was selected for clinical development and obtained marketing authorization as an antihypertensive in several countries.
- Leonardi, Amedeo,Motta, Gianni,Pennini, Renzo,Testa, Rodolfo,Sironi, Giorgio,Catto, Alberto,Cerri, Alberto,Zappa, Marco,Bianchi, Giorgio,Nardi, Dante
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p. 399 - 420
(2007/10/03)
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- Silyl enol ethers as new protecting groups for alkyl 4-halo-3-oxobutanoates; the preparation of pure (3-alkoxycarbonyl-2-oxopropyl)triphenylphosphonium salts
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A new method has been developed for the preparation of pure (3-alkoxycarbonyl-2-oxopropyl)triphenyl-phosphonium salts 8. Alkyl 4-bromo-3-oxobutanoates and alkyl 4-chloro-3-oxobutanoates 7 are protected as the trimethylsilyl enol ethers prior to treatment of the resulting bromo(trimethylsilyl enol ether) esters 20c and 21c with triphenylphosphine in toluene and then addition of a little water to give pure (3-isopropoxycarbonyl-2-oxopropyl)triphenylphosphonium bromide 8c. Bromo(silyl enol ether) esters react more efficiently with triphenylphosphine than the chloro(silyl enol ether) esters. tert-Butyldimethylsilyl enol ethers of alkyl 4-bromo-3-oxobutanoates and alkyl 4-chloro-3-oxobutanoates 7 also react with triphenylphosphine. Protection of isopropyl 4-bromo-3-oxobutanoate 7c as the enol acetate followed by subsequent reaction with triphenylphosphine gives (Z)-(2-acetoxy-3-isopropoxycarbonylbut-2-enyl)triphenylphosphonium bromide 17.
- Moorhoff, Cornelis M.
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p. 1987 - 1995
(2007/10/03)
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- Synthesis and calcium-channel antagonist activity of 4-imidazolyl-1,4-dihydropyridines
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The o-nitrophenyl group at position 4 of dihydropyridine of nifedipine analogues was replaced by 1-methylimidazole. These compounds were evaluated as calcium-channel antagonists using the high K+ contraction of guinea-pig ileal longitudinal smooth muscle. The results for the symmetrical esters showed that increasing the length of methylene chain of ester more than 3 units decreases activity. For cyclic esters, cyclopropylmethyl ester was more active than cyclohexylmethyl ester. Our results revealed two compounds with activities similar to the reference drug nifedipine; the symmetrical cyclopropylmethyl ester, and the asymmetrical phenethyl ethyl derivatives were the most potent antagonists tested.
- Pourmorad,Hadizadeh,Shafiee
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p. 165 - 168
(2007/10/03)
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- The stereoselective preparation of β-hydroxy esters using a yeast reduction in an organic solvent
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A range of (S)-β-hydroxy esters has been prepared in high yield (56-96%) and with very high enantioselectivity (>94%) using a yeast mediated reduction in light petroleum. It was found that the ester functionality had a marked effect on both the isolated yield and the quantity of yeast required to effect complete reduction.
- Medson, Caroline,Smallridge, Andrew J.,Trewhella, Maurie A.
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p. 1049 - 1054
(2007/10/03)
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- Chemoselectivity in the Reactions of Acetylketene and Acetimidoylketene: Confirmation of Theoretical Predictions
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Acetylketene (1) was generated by flash pyrolysis of 2,2,6-trimethyl-4H-1,3-dioxin-4-one (6). The selectivities of 1 toward a number of representative functional groups were measured for the first time in a series of competitive trapping reactions. The trend in reactivities toward 1 follows the general order amines > alcohols aldehydes ≈ ketones and can be rationalized by considering both the nucleophilicity and the electrophilicity of the reacting species. Alcohols show significant selectivity based on steric hindrance, with MeOH ≈ 1° > 2° > 3°. These selectivities are consistent with the activation energies and the pseudopericyclic transition structure previously calculated for the addition of water to formylketene. The results, presented here, of ab initio transition structure calculations for the addition of ammonia to formylketene are qualitatively consistent with the experimental trends as well. N-Propylacetacetimidoylketene (2) was generated by the solution pyrolysis of tert-butyl N-propyl-3-amino-2-butenoate (9a) and showed similar selectivity toward alcohols as opposed to ketones and similar steric discrimination toward alcohols. This is again in agreement with previous ab initio calculations. Taken together, these experimental trends in the reactivities of both 1 and 2 toward a variety of reagents provide strong, although indirect support for the planar, pseudopericyclic transition structures for these reactions which are predicted by ab initio calculations.
- Birney, David M.,Xu, Xiaolian,Ham, Sihyun,Huang, Xiaomeng
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p. 7114 - 7120
(2007/10/03)
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- Novel 2-amino-1,4-dihydropyridine calcium antagonists. I. Synthesis and antihypertensive effects of 2-amino-1,4-dihydropyridine derivatives having nitroxyalkoxycarbonyl groups at 3- and/or 5-position
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Novel 2-amino-1,4-dihydropyridine derivatives, which contain nitroxy-alkoxycarbonyl groups at the 3- and/or 5-position, were synthesized and their pharmaceutical effect was evaluated in spontaneously hypertensive rats. The structure-activity relationships are discussed in terms of potency, onset-rapidity, and duration of antihypertensive activity. Remarkably prolonged duration of antihypertensive action was observed when a tertiary amino group was introduced on either side of an ester chain.
- Kobayashi,Inoue,Kita,Yoshiya,Nishino,Oizumi,Kimura
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p. 788 - 796
(2007/10/02)
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- Novel 2-amino-1,4-dihydropyridine calcium antagonists. II. Synthesis and antihypertensive effects of 2-amino-1,4-dihydropyridine derivatives having N,N-dialkylaminoalkoxycarbonyl groups at 3- and/or 5-positions
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Novel 2-amino-1,4-dihydropyridine derivatives I, which contain N,N-dialkylaminoalkoxycarbonyl groups at the 3- and/or 5-position, were synthesized and their antihypertensive effects were evaluated in spontaneously hypertensive rats. Remarkably prolonged duration of antihypertensive action was observed when a tertiary amino group was introduced into either the 3- or 5-ester side-chain of the 1,4-dihydropyridine ring. In particular, the compounds containing cyclic amino moieties at the 3-position showed greater potency than those with acyclic amino moieties. Chemical modification studies indicated that the two ester side-chains of 1,4-dihydropyridine at the 3- and 5-position might function in a different manner in relation to the antihypertensive activities. 3-(1-Benzhydrylazetidin-3-yl) 5-isopropyl 2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxyl ate, I-43 (CS-905), exhibited potent and long-lasting antihypertensive effects with gradual onset of action, and is a promising candidate as an antihypertensive drug.
- Kobayashi,Inoue,Nishino,Fujihara,Oizumi,Kimura
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p. 797 - 817
(2007/10/02)
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- Reactive dyes which contain a triazinyl group linked to a substituted alkyl group and an amino group which contains a vinylsulfone-type reactive radical
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Water-soluble dyes, such as, for example, azo dyes, heavy metal complex azo dyes, anthraquinone, phthalocyanine and formazan dyes containing the group of the formula STR1 are described, in which Rx is hydrogen or substituted or unsubstituted lower alkyl, U is hydrogen, cyano, lower alkanoyl, lower alkoxycarbonyl, nitro, lower alkylsulfonyl or substituted or unsubstituted arylsulfonyl, V is cyano, lower alkoxycarbonyl, substituted or unsubstituted aryloxycarbonyl, carboxy, lower alkylaminocarbonyl, substituted or unsubstituted arylaminocarbonyl, lower alkylcarbonyl, substituted or unsubstituted arylcarbonyl or arylsulfonyl, aminocarbonyl, dialkylaminocarbonyl, trifluoromethyl, nitro or lower alkylsulfonyl and Q is an amino group which is mono- or disubstituted by the radical --W--(SO2 --Y)z, in which W is an arylene or alkylene radical or a combination of such radicals, the alkylene radicals being those having 1 to 8 carbon atoms, and it being possible for them to be substituted, and the arylene radicals being substituted or unsubstituted phenylene or napthylene radicals, it being possible for the alkylene radicals to be interrupted by one or more hetero groups and for the alkylene and arylene moieties in the combined alkylene/arylene radicals to be separated from one another by a hetero group, the radical --SO2 --Y is a fiber-reactive group from the vinylsulfone series and z is a number 1 or 2, or Q is an nitrogen-containing radical which is bound to the triazine radical via the nitrogen atom and contains a fiber-reactive group from the vinylsulfone series bound via a lower alkylene radical. The dyes are suitable for dyeing hydroxy and/or carboxamido-containing material, in particular fiber material.
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- Substituted biphenyls
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Substituted biphenyls can be prepared by reduction of appropriate ketones and, if appropriate, subsequent hydrolysis, cyclization, hydrogenation and separation of isomers. The substituted biphenyls can be used as active compounds in medicaments.
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- Calcium channel blocking and positive inotropic activities of ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(phenylsulfonyl)methyl]-4-aryl-3-pyrid ine-carboxylate and analogues. Synthesis and structure-activity relationships
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The synthesis and pharmacological evaluation of a series of 2-[(arylsulfonyl)methyl]-4-aryl-5-cyano-1,4-dihydropyridine-3-carboxyl ic acid esters and analogues are described. These compounds possess a unique profile namely, calcium channel blocking and positive inotropic activities in vitro. Compound 54 was selected as the best compound in the series and was studied in detail. The synthesis and biological profiles of enantiomers of 54 are also reported. The data indicate that although the calcium channel blocking property of 54 is stereospecific the positive inotropic activity is not. Examples of 3- and 6-cyano and other closely related 1,4-dihydropyridine derivatives are described and evaluated for comparison and were found to be devoid of dual activities mentioned above.
- Sircar,Gregor,Anderson,Haleen,Shih,Weishaar,Steffen,Pugsley,Taylor
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p. 2248 - 2260
(2007/10/02)
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- Synthesis of (+/-)-karahana ether and a (+/-)-labdadienoic acid by the electrophilic cyclization of epoxy allylsilanes
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The epoxy allylsilanes 7 and 16 were synthesized by stereoselective routes from β-keto esters and cyclized with Lewis acids in good yield.The monocyclic product from 7 was converted into (+/-)-karahana ether (10), and the bicyclic product from 20 was used in a synthesis of the 3-hydroxylabdadienoic acid 24b.
- Armstrong, Rosemary J.,Weiler, Larry
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p. 584 - 596
(2007/10/02)
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- Oxygen Nucleophile Induced Ring Cleavage of 6-Methyl-1,3-oxazine-2,4(3H)-dione -- A Case of Nucleophilic Attack at C-4
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Alcohols in the presence of triethylamine react with 6-methyl-1,3-oxazine-2,4(3H)-dione (2), preferentially at C-4 instead of C-2 to afford the corresponding alkyl acetoacetates (4), and alkyl carbamates (5).
- Singh, Harjit,Kumar, Subodh
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- Nimodipine: Synthesis and metabolic pathway
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Key step of the synthesis of the calcium antagonistic cerebral vasodilator (±) isopropyl-2-methoxyethyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (Bay e 9736, nimodipine) is the cyclising Michael addition. A pharmacokinetic study with 14C-nimodipine in the rat revealed as major metabolites the dihydropyridines as well as the pyridines. A potential metabolic pathway is discussed involving ether cleavage and oxidation to the pyridine form as primary biotransformation steps. Reference metabolites were synthesized using 1,4-dihydropyridines with appropriate functionalities as precursors.
- Meyer,Wehinger,Bossert,Scherling
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p. 106 - 112
(2007/10/02)
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- Macrocyclic Lactone Formation through Sulfide Contraction. Synthesis of (+/-)-Diplodialide A
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A methodology for the synthesis of macrocyclic β-keto-lactones from ω-hydroxy thioamides is described.The hydroxy thioamides were esterified with chloroacetyl chloride, and the resulting chloro esters underwent Eschenmoser sulfide contraction when treated with sodium iodide, diisopropylethylamine, and triethyl phosphite in acetonitrile.The β-keto lactones were obtained in 25-58 percent yield.The utility of the method was demonstrated by synthesis of diplodialide A.
- Ireland, Robert E.,Brown, Frank R.
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p. 1868 - 1880
(2007/10/02)
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- 1,4-Dihydropyridine esters
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A new class of 1,4-dihydropyridines which are characterized by the presence of ester substitutes at positions 3 and 5 of the nucleus and by the presence of an alkoxyalkyl at position 2. The products exhibit coronary activity and have particular application as coronary dilators, antifibrillators, anti-hypertensives, and as muscular and vascular spasmolytics.
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- 1,4-Dihydropyridine carboxylic acid esters useful as coronary vessel dilators and anti-hypertensives
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Certain 1,4-dihydropyridine carboxylic acid esters or their pharmaceutically acceptable non toxic salts are useful as coronary vessel dilators and antihypertensives.
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