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1.
Quinolone Analogs 13: Synthesis of Novel 1,1′‐(2‐Methylenepropane‐1,3‐diyl)di(4‐quinolone‐3‐carboxylate) and Related Compounds
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Yoshihisa Kurasawa Kiminari Yoshida Naoki Yamazaki Eisuke Kaji Kenji Sasaki Yoshito Zamami Takatoshi Fujii Min Zhao Hideyuki Ito Haruhiko Fukaya 《Journal of heterocyclic chemistry》2014,51(6):1720-1726
The reaction of the 4‐hydroxyquinoline‐3‐carboxylate 6 with pentaerythritol tribromide gave the 1,1′‐(2‐methylenepropane‐1,3‐diyl)di(4‐quinolone‐3‐carboxylate) 11 , whose reaction with bromine afforded the 1,1′‐(2‐bromo‐2‐bromomethylpropane‐1,3‐diyl)di(4‐quinolone‐3‐carboxylate) 12 . Compound 12 was transformed into the (Z)‐1,1′‐(2‐acetoxymethylpropene‐1,3‐diyl)di(4‐quinolone‐3‐carboxylate) 13 or (E)‐1,1′‐[2‐(imidazol‐1‐ylmethyl)propene‐1,3‐diyl]di(4‐quinolone‐3‐carboxylate) 14 . Hydrolysis of the dimer (Z)‐ 13 or (E)‐ 14 with potassium hydroxide provided the (E)‐1,1′‐(2‐hydroxymethylpropene‐1,3‐diyl)di(4‐quinolone‐3‐carboxylic acid) 15 or (Z)‐1,1′‐[2‐(imidazol‐1‐ylmethyl)propene‐1,3‐diyl]di(4‐quinolone‐3‐carboxylic acid) 16 , respectively. The nuclear Overhauser effect (NOE) spectral data supported that those hydrolysis resulted in the geometrical conversion of (Z)‐ 13 into (E)‐ 15 or (E)‐ 14 into (Z)‐ 16 . 相似文献
2.
Concise Approach to (ent)‐14 β‐Hydroxysteroids through Highly Diastereo‐/Enantioselective Diels–Alder Reactions
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Clovis Peter Dr. Blandine Ressault Dr. Philippe Geoffroy Dr. Michel Miesch 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(31):10808-10812
14β‐Hydroxysteroids, especially 14β‐hydroxyandrostane derivatives are closely related to the cardenolide skeletons. The latter were readily available through highly diastero/enantioselective Diels–Alder (DA) reactions requiring high pressure or Lewis acid activation. Moreover, in the presence of (R)‐ or (S)‐carvone as a chiral dienophile, the DA‐reaction takes place under chemodivergent parallel kinetic resolution control affording highly enantiomerically enriched 14β‐hydroxysteroid derivatives or the corresponding (ent)‐14β‐hydroxysteroid derivatives. 相似文献
3.
Optical resolution of racemic 5‐oxo‐1‐phenyl‐pyrazolidine‐3‐carboxylic acid 2 with L‐amino acid methyl ester via the diastereomers formation was investigated. Treatment of racemic 5‐oxo‐1‐phenyl‐pyrazolidine‐3‐carboxylic acid 2 with L‐valine methyl ester gave diastereomers with a total yield of 86%. The diastereomeric dipeptides can be easily separated by flash column chromatography. Acidic cleavage of the derived diastereomers gave both the optically pure (+)‐(R)‐ and (‐)‐(S)‐5‐oxo‐1‐phenyl‐pyrazolidine‐3‐carboxylic acid ((+)‐(R)‐ 2 and (‐)‐(S)‐ 2 ) with a total yield of 94% and 95%, respectively. 相似文献
4.
Cheng‐Jian Tan Ping Yi Masuo Goto Susan L. Morris‐Natschke Li‐Na Liu Kuo‐Hsiung Lee Bao‐Yu Zhao 《Helvetica chimica acta》2016,99(3):225-227
A new matrine alkaloid derivative (+)‐(14β)‐14‐ethylmatridin‐15‐one ( 1 ) was isolated from the poisonous plant Oxytropis ochrocephala Bunge . The structure was established by spectroscopic methods, including extensive 1D‐ and 2D‐NMR experiments. 相似文献
5.
Peter Grundt Fernando Martinez‐Bermejo JohnW. Lewis StephenM. Husbands 《Helvetica chimica acta》2003,86(3):793-798
A series of 14β‐alkyl‐ and 14β‐alkenyl‐5β‐methylindolomorphinans was synthesized and evaluated in opioid binding and functional assays. While being relatively nonselective in binding assays, the 14‐cinnamyl and 14‐isopentyl members showed selective opioid δ‐receptor partial agonist activity in [35S]GTPγS assays. 相似文献
6.
Dieter Seebach Bernhard Jaun Radovan Sebesta RaveendraI. Mathad Oliver Flgel Michael Limbach Holger Sellner Sylvain Cottens 《Helvetica chimica acta》2006,89(9):1801-1825
Twelve peptides, 1 – 12 , have been synthesized, which consist of alternating sequences of α‐ and β‐amino acid residues carrying either proteinogenic side chains or geminal dimethyl groups (Aib). Two peptides, 13 and 14 , containing 2‐methyl‐3‐aminobutanoic acid residues or a ‘random mix’ of α‐, β2‐, and β3‐amino acid moieties were also prepared. The new compounds were fully characterized by CD (Figs. 1 and 2), and 1H‐ and 13C‐NMR spectroscopy, and high‐resolution mass spectrometry (HR‐MS). In two cases, 3 and 14 , we discovered novel types of turn structures with nine‐ and ten‐membered H‐bonded rings forming the actual turns. In two other cases, 8 and 11 , we found 14/15‐helices, which had been previously disclosed in mixed α/β‐peptides containing unusual β‐amino acids with non‐proteinogenic side chains. The helices are formed by peptides containing the amino acid moiety Aib in every other position, and their backbones are primarily not held together by H‐bonds, but by the intrinsic conformations of the containing amino acid building blocks. The structures offer new possibilities of mimicking peptide–protein and protein–protein interactions (PPI). 相似文献
7.
Biswanath Das D. Nandan Kumar Keetha Laxminarayana B. Ravikanth 《Helvetica chimica acta》2007,90(7):1330-1334
The synthesis of 14‐aryl‐ or 14‐alkyl‐14H‐dibenzo[a,j]xanthenes 3 involving the treatment of naphthalen‐2‐ol ( 1 ) with arenecarboxaldehydes or alkanals 2 in the presence of HClO4?SiO2 as a heterogeneous catalyst was achieved (Table 1), and this reaction was extended to the preparation of N‐[(2‐hydroxynaphthalen‐1‐yl)methyl]amides 5 by a three‐component reaction with urea ( 4a ) or an amide 4b – d as a third reactant (Table 2). 相似文献
8.
The heterospirocyclic N‐methyl‐N‐phenyl‐5‐oxa‐1‐azaspiro[2.4]hept‐1‐e n‐2‐amine (6 ) and N‐(5‐oxa‐1‐azaspiro[2.4]hept‐1‐en‐2‐yl)‐(S)‐proline methyl ester ( 7 ) were synthesized from the corresponding heterocyclic thiocarboxamides 12 and 10 , respectively, by consecutive treatment with COCl2, 1,4‐diazabicyclo[2.2.2]octane, and NaN3 (Schemes 1 and 2). The reaction of these 2H‐azirin‐3‐amines with thiobenzoic and benzoic acid gave the racemic benzamides 13 and 14 , and the diastereoisomeric mixtures of the N‐benzoyl dipeptides 15 and 16 , respectively (Scheme 3). The latter were separated chromatographically. The configurations and solid‐state conformations of all six benzamides were determined by X‐ray crystallography. With the aim of examining the use of the new synthons in peptide synthesis, the reactions of 7 with Z‐Leu‐Aib‐OH to yield a tetrapeptide 17 (Scheme 4), and of 6 with Z‐Ala‐OH to give a dipeptide 18 (Scheme 5) were performed. The resulting diastereoisomers were separated by means of MPLC or HPLC. NMR Studies of the solvent dependence of the chemical shifts of the NH resonances indicate the presence of an intramolecular H‐bond in 17 . The dipeptides (S,R)‐ 18 and (S,S)‐ 18 were deprotected at the N‐terminus and were converted to the crystalline derivatives (S,R)‐ 19 and (S,S)‐ 19 , respectively, by reaction with 4‐bromobenzoyl chloride (Scheme 5). Selective hydrolysis of (S,R)‐ 18 and (S,S)‐ 18 gave the dipeptide acids (R,S)‐ 20 and (S,S)‐ 20 , respectively. Coupling of a diastereoisomeric mixture of 20 with H‐Phe‐OtBu led to the tripeptides 21 (Scheme 5). X‐Ray crystal‐structure determinations of (S,R)‐ 19 and (S,S)‐ 19 allowed the determination of the absolute configurations of all diastereoisomers isolated in this series. 相似文献
9.
LC/MS3‐Guided biotransformation of p‐coumaric acid (=(2E)‐3‐(4‐hydroxyphenyl)prop‐2‐enoic acid; CA) with H2O2/Momordica charantia peroxidase at pH 5.0 and 45° in the presence of acetone has resulted in the isolation of three CA trimers, triCA1 ( 1 ), triCA2 (trans‐ 2 ), and triCA3 (cis‐ 2 ), and seven CA dimers, diCA1–diCA7, i.e., 3 – 9 , among which seven (triCA1–triCA3 and diCA1–diCA4) are new compounds and three (diCA5–diCA7) are known compounds. The structures were established by 2D‐NMR such as HSQC, HMBC, and NOESY measurements. The possible mechanism for the formation of the products is also discussed (Schemes 1–3). This is the first time that the biotansformation of p‐coumaric acid catalyzed by peroxidase in vitro was achieved. Compounds triCA3 (cis‐ 2 ), diCA1 ( 3 ), diCA5 ( 7 ), and diCA7 ( 9 ) exhibit a stronger antioxidative activity than the parent CA. 相似文献
10.
Thomas Baumann Reinhard Brückner 《Angewandte Chemie (International ed. in English)》2019,58(14):4714-4719
On the 1H NMR timescale, 2,2′‐biindolyls with (R)‐configured (1‐alkoxyprop)‐2‐yl, (1‐hydroxyprop)‐2‐yl, or (1‐siloxyprop)‐2‐yl substituents at C‐1 and C‐1′ are atropisomerically stable at <0 °C and interconvert at >30 °C. A 2,2′‐biindolyl (R,R)‐ 17 a of that kind and achiral (!) brominating reagents gave the atropisomerically stable 3,3′‐dibromobiindolyls (M)‐ and/or (P)‐ 18 a at best atropselectively—because of point‐to‐axial asymmetric inductions—and atropdivergently, exhibiting up to 95 % (M)‐ and as much (P)‐atropselectivity. This route to atropisomerically pure biaryls is novel and should extend to other substrates and/or different functionalizations. The dibromobiindolyls (M)‐ and (P)‐ 18 a furnished the biindolyldiphosphanes (M)‐ and (P)‐ 14 without atropisomerization. These syntheses did not require the resolution of a racemic mixture, which distinguishes them from virtually all biaryldiphosphane syntheses known to date. (M)‐ and (P)‐ 14 acted as ligands in catalytic asymmetric allylations and hydrogenations. Remarkably, the β‐ketoester rac‐ 25 c was hydrogenated trans‐selectively with 98 % ee; this included a dynamic kinetic resolution. 相似文献
11.
Elisabetta Brenna Marco Delmonte Claudio Fuganti Stefano Serra 《Helvetica chimica acta》2001,84(1):69-86
The (−)‐ and (+)‐β‐irones ((−)‐ and (+)‐ 2 , resp.), contaminated with ca. 7 – 9% of the (+)‐ and (−)‐trans‐α‐isomer, respectively, were obtained from racemic α‐irone via the 2,6‐trans‐epoxide (±)‐ 4 (Scheme 2). Relevant steps in the sequence were the LiAlH4 reduction of the latter, to provide the diastereoisomeric‐4,5‐dihydro‐5‐hydroxy‐trans‐α‐irols (±)‐ 6 and (±)‐ 7 , resolved into the enantiomers by lipase‐PS‐mediated acetylation with vinyl acetate. The enantiomerically pure allylic acetate esters (+)‐ and (−)‐ 8 and (+)‐ and (−)‐ 9 , upon treatment with POCl3/pyridine, were converted to the β‐irol acetate derivatives (+)‐ and (−)‐ 10 , and (+)‐ and (−)‐ 11 , respectively, eventually providing the desired ketones (+)‐ and (−)‐ 2 by base hydrolysis and MnO2 oxidation. The 2,6‐cis‐epoxide (±)‐ 5 provided the 4,5‐dihydro‐4‐hydroxy‐cis‐α‐irols (±)‐ 13 and (±)‐ 14 in a 3 : 1 mixture with the isomeric 5‐hydroxy derivatives (±)‐ 15 and (±)‐ 16 on hydride treatment (Scheme 1). The POCl3/pyridine treatment of the enantiomerically pure allylic acetate esters, obtained by enzymic resolution of (±)‐ 13 and (±)‐ 14 , provided enantiomerically pure cis‐α‐irol acetate esters, from which ketones (+)‐ and (−)‐ 22 were prepared (Scheme 4). The same materials were obtained from the (9S) alcohols (+)‐ 13 and (−)‐ 14 , treated first with MnO2, then with POCl3/pyridine (Scheme 4). Conversely, the dehydration with POCl3/pyridine of the enantiomerically pure 2,6‐cis‐5‐hydroxy derivatives obtained from (±)‐ 15 and (±)‐ 16 gave rise to a mixture in which the γ‐irol acetates 25a and 25b and 26a and 26b prevailed over the α‐ and β‐isomers (Scheme 5). The (+)‐ and (−)‐cis‐γ‐irones ((+)‐ and (−)‐ 3 , resp.) were obtained from the latter mixture by a sequence involving as the key step the photochemical isomerization of the α‐double bond to the γ‐double bond. External panel olfactory evaluation assigned to (+)‐β‐irone ((+)‐ 2 ) and to (−)‐cis‐γ‐irone ((−)‐ 3 ) the strongest character and the possibility to be used as dry‐down note. 相似文献
12.
James Gardiner Raveendra I. Mathad Berhard Jaun Jürg V. Schreiber Oliver Flögel Dieter Seebach 《Helvetica chimica acta》2009,92(12):2698-2721
β3‐Peptides consisting of six, seven, and ten homologated proteinogenic amino acid residues have been attached to an α‐heptapeptide (all d‐ amino acid residues; 4 ), to a hexaethylene glycol chain (PEGylation; 5c ), and to dipicolinic acid (DPA derivative 6 ), respectively. The conjugation of the β‐peptides with the second component was carried out through the N‐termini in all three cases. According to NMR analysis (CD3OH solutions), the (M)‐314‐helical structure of the β‐peptidic segments was unscathed in all three chimeric compounds (Figs. 2, 4, and 5). The α‐peptidic section of the α/β‐peptide was unstructured, and so was the oligoethylene glycol chain in the PEGylated compound. Thus, neither does the appendage influence the β‐peptidic secondary structure, nor does the latter cause any order in the attached oligomers to be observed by this method of analysis. A similar conclusion may be drawn from CD spectra (Figs. 1, 3, and 5). These results bode well for the development of delivery systems involving β‐peptides. 相似文献
13.
Regio‐ and Enantio‐selective Chemo‐enzymatic C−H‐Lactonization of Decanoic Acid to (S)‐δ‐Decalactone
Jack Manning Michele Tavanti Joanne L. Porter Nico Kress Sam P. DeVisser Nicholas J. Turner Sabine L. Flitsch 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(17):5724-5727
The conversion of saturated fatty acids to high value chiral hydroxy‐acids and lactones poses a number of synthetic challenges: the activation of unreactive C?H bonds and the need for regio‐ and stereoselectivity. Here the first example of a wild‐type cytochrome P450 monooxygenase (CYP116B46 from Tepidiphilus thermophilus) capable of enantio‐ and regioselective C5 hydroxylation of decanoic acid 1 to (S)‐5‐hydroxydecanoic acid 2 is reported. Subsequent lactonization yields (S)‐δ‐decalactone 3 , a high value fragrance compound, with greater than 90 % ee. Docking studies provide a rationale for the high regio‐ and enantioselectivity of the reaction. 相似文献
14.
Srivari Chandrasekhar Birudaraju Saritha Police Naresh Marelli Udayakiran Chada Raji Reddy Bharatam Jagadeesh 《Helvetica chimica acta》2008,91(7):1267-1276
The conformational control of a 14‐helix nucleating template, cis‐β‐furanoid sugar amino acid (FSAA), over a flexible δ‐amino acid, ornithine is studied in a FSAA‐ornithine cyclic tetrapeptide. Extensive NMR and MD studies reveal that the cyclic peptide adopts a three‐dimentional bowl‐shape cavity, which promotes six‐ and seven‐membered intra‐ and inter‐residue H‐bonding, in polar and non‐polar solvents, respectively. 相似文献
15.
Synthesis of Novel,Chiral Bicyclo[3.1.0]hex‐2‐ene Amino Acid Derivatives as Useful Synthons in Medicinal Chemistry
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Heinz Stadler 《Helvetica chimica acta》2015,98(9):1189-1201
A short and concise synthesis of novel, chiral bicyclo[3.1.0]hex‐2‐ene amino acid derivatives 13 and 14 has been developed. The key step is a stereo‐ and regioselective allylic amination of exo‐ and endo‐methyl bicyclo[3.1.0]hex‐2‐ene‐6‐carboxylates 8 and 9 , which were prepared from 7,7‐dichlorobicyclo[3.2.0]hept‐2‐en‐6‐one ( 1 ). These amino acid derivatives are useful building blocks in medicinal chemistry and can be prepared as chiral compounds by using either (+)‐ 1 or (?)‐ 1 as starting material. 相似文献
16.
3-氨甲酰甲基-5-甲基-己酸经拆分后得到的(R)-构型体是合成抗癫痫药物普瑞巴林(pregabalin, PGB)的关键中间体,余下的对映体(S)-构型体一般经酸化成无手性中心的3-异丁基戊二酸后再通过化学反应使之生成3-氨甲酰甲基-5-甲基-己酸的消旋体以重复利用,该方法步骤较多,费时较长(约40小时),收率只有29.5%。本文在二甲苯中加热(S)-构型体,使之转化为3-异丁基戊二酰亚胺,后者在氢氧化钠水溶液中经水解得到3-氨甲酰甲基-5-甲基-己酸的消旋体。此方法耗时短(约20小时)且收率高(76.4%)。 相似文献
17.
Johannes Schütz Wolfgang Brandt Mariana Spetea Klaus Wurst Gerhard Wunder Helmut Schmidhammer 《Helvetica chimica acta》2003,86(6):2142-2148
The novel morphinans 13 – 18 , which carry amino acid substituents at C(6), with potentially limited access to the central nervous system were prepared in two steps from 14‐O‐methyloxymorphone ( 5 ). Reductive amination with amino acid tert‐butyl esters gave compounds 7 – 12 , which were hydrolyzed with tetrafluoroboric acid. Structure elucidation (including X‐ray analysis), preliminary μ‐opioid receptor binding studies, and calculations of pharmacokinetic parameters were carried out. 相似文献
18.
An optically active α‐ethylated α,α‐disubstituted amino acid, (S)‐butylethylglycine (=(2S)‐2‐amino‐2‐ethylhexanoic acid; (S)‐Beg; (S)‐ 2 ), was prepared starting from butyl ethyl ketone ( 1 ) by the Strecker method and enzymatic kinetic resolution of the racemic amino acid. Homooligopeptides containing (S)‐Beg (up to hexapeptide) were synthesized by conventional solution methods. An ethyl ester was used for the protection at the C‐terminus, and a trifluoroacetyl group was used for the N‐terminus of the peptides. The structures of tri‐ and tetrapeptides 5 and 6 in the solid state were solved by X‐ray crystallographic analysis, and were shown to have a bent planar C5‐conformation (tripeptide) and a fully planar C5‐conformation (tetrapeptide) (see Figs. 1 and 2, resp.). The IR and 1H‐NMR spectra of hexapeptide 8 revealed that the dominant conformation in CDCl3 solution was also a fully planar C5‐conformation. These results show for the first time that the preferred conformation of homopeptides containing a chiral α‐ethylated α,α‐disubstituted amino acid is a planar C5‐conformation. 相似文献
19.
The title bis(phosphane) ligands have been prepared starting from optically pure diisopropyl (P)‐ and (M)‐8,12‐diphenylbenzo[a]heptalene‐6,7‐dicarboxylates ((P)‐ 1b and (M)‐ 1b ) that had been obtained by HPLC separation of rac‐ 1b on a semi‐preparative Chiralcel OD column. Reduction of (P)‐ 1b and (M)‐ 1b with diisobutylaluminum hydride (DIBAH) gave optically pure (P)‐ and (M)‐dimethanols 3 (Scheme 6 and Fig. 5). Unfortunately, the almost quantitative chlorination of rac‐ 3 with PCl5 in CHCl3 at −60° led with (M)‐ 3 to nearly complete loss of optical integrity. However, mesylate formation of (P)‐ 3 , followed by phosphanylation with LiP(BH3)Ph2 gave (P)‐ 6 with only a small loss of optical activity. Optically pure (P)‐ 6 was obtained by crystallization from Et2O/hexane, which removed the nearly insoluble rac‐ 6 . The pure bis(phosphane) ligands (P)‐ 2 and (M)‐ 2 can be liberated quantitatively from 6 by warming 6 in toluene in the presence of 1,4‐diazabicyclo[2.2.2]octane (DABCO). First RhI‐catalyzed asymmetric hydrogenation reactions of (Z)‐α‐(acetamido)cinnamic acid ((Z)‐ 14 ) in the presence of (P)‐ 2 led to (R)‐N‐acetylphenylalanin ((R)‐ 15 ) in optical purities up to 77% (see Table 1). 相似文献
20.
The crystal structures of salt 8 , which was prepared from (R)‐2‐methoxy‐2‐(2‐naphthyl)propanoic acid ((R)‐MβNP acid, (R)‐ 2 ) and (R)‐1‐phenylethylamine ((R)‐PEA, (R)‐ 6 ), and salt 9 , which was prepared from (R)‐2‐methoxy‐2‐(1‐naphthyl)propanoic acid ((R)‐MαNP acid, (R)‐ 1 ) and (R)‐1‐(p‐tolyl)ethylamine ((R)‐TEA, (R)‐ 7 ), were determined by X‐ray crystallography. The MβNP and MαNP anions formed ion‐pairs with the PEA and TEA cations, respectively, through a methoxy‐group‐assisted salt bridge and aromatic CH???π interactions. The networks of salt bridges formed 21 columns in both salts. Finally, (S)‐(2E,6E)‐(1‐2H1)farnesol ((S)‐ 13 ) was prepared from the reaction of (2E,6E)‐farnesal ( 11 ) with deuterated (R)‐BINAL‐H (i.e., (R)‐BINAL‐D). The enantiomeric excess of compound (S)‐ 13 was determined by NMR analysis of (S)‐MαNP ester 14 . The solution‐state structures of MαNP esters that were prepared from primary alcohols were also elucidated. 相似文献