- Antitubercular agents. Part 2: New thiolactomycin analogues active against Mycobacterium tuberculosis
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Structurally modified analogues of naturally occurring antibiotic thiolactomycin, substituted at 4-position of the thiolactone ring have been prepared and evaluated for their antitubercular activity. Some of the compounds have exhibited potential activity against Mycobacterium tuberculosis.
- Kamal, Ahmed,Ali Shaik, Ahmad,Sinha, Rakesh,Yadav,Arora, Sudarshan K.
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- Origins of stereoselectivity in the α-alkylation of chiral hydrazones
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Density functional theory calculations and experiment reveal the origin of stereoselectivity in the deprotonation-alkylation of chiral N-amino cyclic carbamate (ACC) hydrazones. When the ACC is a rigid, camphor-derived carbamate, the two conformations of the azaenolate intermediate differ in energy due to conformational effects within the oxazolidinone ring and steric interactions between the ACC and the azaenolate. An electrophile adds selectively to the less-hindered π-face of the azaenolate. Although it was earlier reported that use of ACC auxiliaries led to α-alkylated ketones with er values of 82:18 to 98:2, B3LYP calculations predict higher stereoselectivity. Direct measurement of the dr of an alkylated hydrazone prior to removal of the auxiliary confirms this prediction; the removal of the auxiliary under the reported conditions can compromise the overall stereoselectivity of the process.
- Krenske, Elizabeth H.,Houk,Lim, Daniel,Wengryniuk, Sarah E.,Coltart, Don M.
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- Convenient and efficient syntheses of β-keto esters and β-keto amides directly from α-alkylacetyl chlorides
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The α-alkylacetyl chlorides were slowly treated with dried triethylamine, followed by treatment with alcohols or amines, to produce β-keto esters or β-keto amides, respectively. The process is a convenient alternative to prepare β-keto esters and β-keto amides.
- Sung,Wu
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- Chemoenzymatic synthesis of (5S)- and (5R)-hydroxymethyl-3,5-dimethyl-4-(methoxymethoxy)-5H-thiophen-2-one: a precursor of thiolactomycin and determination of its absolute configuration
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A convenient enantioselective synthesis of (5S)- and (5R)-hydroxymethyl-3,5-dimethyl-4-(methoxymethoxy)-5H-thiophen-2-one, a key intermediate in the synthesis of thiolactomycin has been carried out by a Carica papaya lipase-mediated resolution protocol to
- Kamal, Ahmed,Shaik, Ahmad Ali,Azeeza, Shaik,Malik, M. Shaheer,Sandbhor, Mahendra
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- Formation, Alkylation, and Hydrolysis of Chiral Nonracemic N-Amino Cyclic Carbamate Hydrazones: An Approach to the Enantioselective α-Alkylation of Ketones
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The α-alkylation of ketones is a fundamental synthetic transformation. The development of asymmetric variants of this reaction is important given that numerous natural products, drugs, and related compounds exist as α-functionalized ketones or derivatives thereof. We previously reported our preliminary studies on the development of a new enantioselective ketone α-alkylation procedure using N-amino cyclic carbamate (ACC) auxiliaries. In comparison to other auxiliary-based methods, ACC alkylation offers a number of advantages and is both highly enantioselective and high yielding. Herein, we provide a full account of our studies on the enantioselective ACC ketone α-alkylation method.
- Huynh, Uyen,McDonald, Stacey L.,Lim, Daniel,Uddin, Md. Nasir,Wengryniuk, Sarah E.,Dey, Sumit,Coltart, Don M.
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p. 12951 - 12964
(2018/11/30)
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- Unexpected Direct Synthesis of N-Vinyl Amides through Vinyl Azide–Enolate [3+2] Cycloaddition
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The unexpected synthesis of industrially important N-vinyl amides directly from aldehydes and α,β-unsaturated N-vinyl amides from esters is reported. This reaction probably proceeds through an initial [3+2] azide–enolate cycloaddition involving a vinyl azide generated in situ. A survey of the reaction scope and preliminary mechanistic findings supported by quantum computational analysis are reported, with implications for the future development of atom-efficient amide synthesis. Intriguingly, this study suggests that (cautious) reevaluation of azidoethene as a synthetic reagent may be warranted.
- Choi, Hans,Shirley, Harry J.,Hume, Paul A.,Brimble, Margaret A.,Furkert, Daniel P.
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supporting information
p. 7420 - 7424
(2017/06/13)
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- On the regioselectivity and diastereoselectivity of ACC hydrazone alkylation
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The asymmetric α-allylation of 3-pentanone using several different N-amino cyclic carbamate (ACC) auxiliaries is described. The level of asymmetric induction was found to range from er?=?93:7 to er?=?99:1. The factors that lead to compromised selectivity
- Huynh, Uyen,Uddin, Md. Nasir,Wengryniuk, Sarah E.,McDonald, Stacey L.,Coltart, Don M.
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supporting information
p. 432 - 436
(2017/01/13)
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- Synthesis, antimalarial evaluation and molecular docking studies of some thiolactone derivatives
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In present study novel thiolactone derivatives were designed, synthesized and characterized by various analytical techniques such as IR, 1H NMR, 13C NMR, mass spectral data and elemental analysis. All synthesized compounds were evaluated for in?vitro antimalarial activity against Dd2 and 3d7 strain of P.?falciparum. All synthesized compounds were also subjected for molecular docking study with pf KASI/II enzyme to analyze their binding orientation in the active site of the enzyme. Compounds 5d, 5e, and 5i found to be most potent with IC50 in the range of 0.09–0.19?μM and 0.03–0.04?μM against the Dd2 strain and 3D7 strain respectively as well as they showed good binding affinities with the residues of the active site of pf KASI/II.
- Sainy, Jitendra,Sharma, Rajesh
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p. 350 - 359
(2017/01/10)
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- Regioselective synthesis of substituted piperidine-2,4-diones and their derivatives via Dieckmann cyclisations
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Abstract A flexible route to piperidine-2,4-diones variously substituted at the 6-, 5,6- and 2,6-positions, both with and without 1-substitution, is described; no N-protective group is required. A related regioselective Dieckmann cyclisation is also described that uses Davies' α-methylbenzylamine auxiliary and affords 6-substituted piperidine-2,4-diones enantioselectively.
- Marson, Charles M.,Yau, Kin Cheung
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p. 7459 - 7469
(2015/08/24)
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- Access to enantiopure α-alkyl-β-hydroxy esters through dynamic kinetic resolutions employing purified/overexpressed alcohol dehydrogenases
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α-Alkyl-β-hydroxy esters were obtained via dynamic kinetic resolution (DKR) employing purified or crude E. coli overexpressed alcohol dehydrogenases (ADHs). ADH-A from R. ruber, CPADH from C. parapsilosis and TesADH from T. ethanolicus afforded syn-(2R,3S) derivatives with very high selectivities for sterically not impeded ketones ('small-bulky' substrates), while ADHs from S. yanoikuyae (SyADH) and Ralstonia sp. (RasADH) could also accept bulkier keto esters ('bulky-bulky' substrates). SyADH also provided preferentially syn-(2R,3S) isomers and RasADH showed in some cases good selectivity towards the formation of anti-(2S,3S) derivatives. With anti-Prelog ADHs such as LBADH from L. brevis or LKADH from L. kefir, syn-(2S,3R) alcohols were obtained with high conversions and diastereomeric excess in some cases, especially with LBADH. Furthermore, due to the thermodynamically favoured reduction of these substrates, it was possible to employ just a minimal excess of 2-propanol to obtain the final products with quantitative conversions. Copyright
- Cuetos, Anibal,Rioz-Martinez, Ana,Bisogno, Fabricio R.,Grischek, Barbara,Lavandera, Ivan,De Gonzalo, Gonzalo,Kroutil, Wolfgang,Gotor, Vicente
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supporting information; experimental part
p. 1743 - 1749
(2012/07/28)
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- Dynamic kinetic resolution of α-substituted β-ketoesters catalyzed by Baeyer-Villiger monooxygenases: Access to enantiopure α-hydroxy esters
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BVMOs make a play: The dynamic kinetic resolution of racemic α-alkyl-β-ketoesters was performed through a selective Baeyer-Villiger oxidation employing different Baeyer-Villiger monooxygenases (BVMOs) in mild basic media. The product diesters were obtained with excellent yields and enantioselectivities, and used as precursors for optically active α-hydroxy esters.
- Rioz-Martínez, Ana,Cuetos, Aníbal,Rodríguez, Cristina,De Gonzalo, Gonzalo,Lavandera, Iván,Fraaije, Marco W.,Gotor, Vicente
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supporting information; experimental part
p. 8387 - 8390
(2011/10/09)
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- INDOLE AND AZAINDOLE MODULATORS OF THE ALPHA 7 NACHR
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This invention relates to modulation of the α7 nicotinic acetylcholine receptor (nAChR) by a compound of formula (I) or a pharmaceutically acceptable salt thereof.
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Page/Page column 55
(2011/05/05)
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- Thiadiazole carbamates: Potent inhibitors of lysosomal acid lipase and potential niemann-pick type C disease therapeutics
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Niemann-Pick type C (NPC) disease is a lysosomal storage disorder characterized at the cellular level by abnormal accumulation of cholesterol and other lipids in lysosomal storage organelles. Lysosomal acid lipase (LAL) has been recently identified as a potential therapeutic target for NPC. LAL can be specifically inhibited by a variety of 3,4-disubstituted thiadiazole carbamates. An efficient synthesis of the C(3) oxygenated/C(4) aminated analogues has been developed that furnishes the products in high yields and high degrees of purity. Common intermediates can also be used for the synthesis of the C(3) carbon substituted derivatives. Herein we tested various thiadiazole carbamates, amides, esters, and ketones for inhibition of LAL. In addition, we tested a diverse selection of commercially available non-thiadiazole carbamates. Our studies show that, among the compounds examined herein, only thiadiazole carbamates are effective inhibitors of LAL. We present a mechanism for LAL inhibition by these compounds whereby LAL transiently carbamoylates the enzyme similarly to previously described inhibition of acetylcholinesterase by rivastigmine and other carbamates as well as acylation of various lipases by orlistat.
- Rosenbaum, Anton I.,Cosner, Casey C.,Mariani, Christopher J.,Maxfield, Frederick R.,Wiest, Olaf,Helquist, Paul
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supporting information; experimental part
p. 5281 - 5289
(2010/10/19)
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- HETEROARYLTHIOMETHYL PYRIDINE DERIVATIVE
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The present invention relates to a compound represented by a formula (I): wherein X is a group represented by or the like; Y is a group represented by or the like; and Ar1 is a group represented by or a pharmaceutically acceptable salt thereof.
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Page/Page column 41
(2010/11/17)
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- Stereoselective chemoenzymatic synthesis of sitophilate: a natural pheromone
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The aggregation pheromone of the granary weevil Sitophilus granarius, (2S,3R)-1-ethylpropyl 3-hydroxy-2-methylpentanoate, has been synthesized in 63% total isolated yield and high chemical and enantiomeric purity (98% de, >99% ee) from readily available m
- Kalaitzakis, Dimitris,Kambourakis, Spiros,Rozzell, David J.,Smonou, Ioulia
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p. 2418 - 2426
(2008/03/13)
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- Ti-Crossed-Claisen condensation between carboxylic esters and acid chlorides or acids: A highly selective and general method for the preparation of various β-keto esters
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Ti-crossed-Claisen condensation between a 1:1 mixture of carboxylic esters and acid chlorides promoted by TiCl4-Bu3N-N-methylimidazole proceeded successfully to give various β-keto esters in good yields with excellent selectivities (19 examples, ~48-95% yield; cross/self-selectivity = ~96/4-99/1). The present method was extended to the condensation between a 1:1 mixture of carboxylic acids and carboxylic esters (six examples, ~70-92% yield; cross/self-selectivity = ~91/9-99/1). To demonstrate the utility of the present two Ti-crossed-Claisen condensations, we performed a couple of efficient short-step syntheses of two natural, representative, and useful perfumes, cis-jasmone and (R)-muscone. Copyright
- Misaki, Tomonori,Nagase, Ryohei,Matsumoto, Kunshi,Tanabe, Yoo
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p. 2854 - 2855
(2007/10/03)
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- Analogues of thiolactomycin as potential anti-malarial and anti-trypanosomal agents
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A series of analogues of the naturally occurring antibiotic thiolactomycin (TLM) have been synthesised and evaluated for their ability to inhibit the growth of the malaria parasite, Plasmodium falciparum. Thiolactomycin is an inhibitor of Type II fatty acid synthase which is found in plants and most prokaryotes, but not an inhibitor of Type I fatty acid synthase in mammals. A number of the analogues showed inhibition equal to or greater than TLM. The introduction of hydrophobic alkyl groups at the C3 and C5 positions of the thiolactone ring lead to increased inhibition, the best showing a fourteenfold increase in activity over TLM. In addition, some of the analogues showed activity when assayed against the parasitic protozoa, Trypanosoma cruzi and Trypanosoma brucei.
- Jones, Simon M.,Urch, Jonathan E.,Brun, Reto,Harwood, John L.,Berry, Colin,Gilbert, Ian H.
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p. 683 - 692
(2007/10/03)
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- Benzofurylpyrone derivatives
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There is provided benzofuryl-α-pyrone derivative represented by the following structural formula (I): wherein R1represents a hydrogen atom or an alkyl group of 1 to 5 carbons; R2represents hydrogen, —CO—R5or —SO2/sub
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- The Magnesium Bromide Induced Claisen Condensation Reaction of N-Acylpyrazoles
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N-Acylpyrazoles formed the 5-membered C=O...Mg...N-2 chelate complexes with magnesium bromide which afforded the Claisen condensation products by the action of tertiary amine through the corresponding enolate.
- Kashima, Choji,Takahashi, Katsumi,Fukusaka, Kiyoshi
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p. 1775 - 1778
(2007/10/03)
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- THE SELECTIVE CLAISEN AND DIECKMANN ESTER CONDENSATION PROMOTED BY DICHLOROBIS(TRIFLUOROMETHANESULFONATO)TITANIUM(IV)
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Inter and intramolecular condensations (the Claisen and the Dieckmann condensations) between ester functions have been performed by the combined use of dichlorobis(trifluoromethanesulfonato)titanium(IV) (=dichlorobis(triflato)titanium(IV)) and tertiary amine under mild reaction conditions.These results led to the development of the selective (crossed) Claisen and Dieckmann ester condensation between methoxymethyl ester and methyl ester, in that, dichlorobis(triflato)titanum(IV) contribute to control the direction of the reaction.
- Tanabe, Yoo
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p. 1917 - 1924
(2007/10/02)
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- Alternative Synthesis of (+/-)-Trisporol B wia (+/-)-6-Hydroxymethyl-2,6-dimethyl-2-cyclohexen-1-one
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(+/-)-Methyl 1,3-dimethyl-2-oxo-3-cyclohexene-1-carboxylate (7) was synthesized from methyl propionate via Claisen condensation followed by Robinson annelation with acrolein.Lithium aluminum hydride reduction and manganese dioxide oxidation of 7 gave (+/-
- Takahashi, Shunya,Oritani, Takayuki,Yamashita, Kyohei
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p. 1143 - 1148
(2007/10/02)
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- REACTIONS OF ALLYLIC CARBONATES CATALYZED BY PALLADIUM, RHODIUM, RUTHENIUM, MOLYBDENUM, AND NICKEL COMPLEXES; ALLYLATION OF CARBONUCLEOPHILES AND DECARBOXYLATION-DEHYRDOGENATION
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Allylation of carbonucleophiles with allylic carbonates catalyzed by various transition metal complexes has been studied.Palladium, rhodium, ruthenium, nickel, and molybdenum complexes were found to be active catalysts.The rhodium catalyst showed a different regioselectivity from the other catalysts, the reaction can proceed without allylic rearrangement.In the absence of nucleophiles, allyl alkyl carbonates were converted into ketones by decarboxylation-dehydrogenation; the ruthenium catalyst was the most active in this reaction.
- Minami, Ichiro,Shimizu, Isao,Tsuji, Jiro
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p. 269 - 280
(2007/10/02)
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- DICHLORO-BIS(TRIFLUOROMETHANESULFONATO)TITANIUM(IV) AS AN EFFECTIVE PROMOTER IN THE CLAISEN ESTER CONDENSATION
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Inter- and intra-molecular condensation (the Claisen and the Dieckmann condensations) between ester functions have been effected by the combined use of dichloro-bis(trifluoromethanesulfonato)titanium(IV) and tertiary amine under mild conditions.
- Tanabe, Yoo,Mukaiyama, Teruaki
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p. 1867 - 1870
(2007/10/02)
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- REFORMATSKY INTERMEDIATE. A C-METALLED SPECIES.
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13C-NMR and 1H-NMR spectra of the Reformatsky reagent from t-butylbromoacetate, evidence a C-metalled species: within the limits of detectability of the methods, no O-metallated species can be detected in solution.
- Orsini, F.,Pelizzoni, F.,Ricca, G.
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p. 3945 - 3948
(2007/10/02)
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