Showing papers on "Epimer published in 2002"
TL;DR: Several synthetic intermediates and spirotryprostatin analogs were tested for their activity as G2/M phase cell cycle inhibitors and microtuble assembly against 3Y1 and tsFT210 mammalian cells.
95 citations
TL;DR: In this paper, the formation of Zn-enolate that is stabilized by intramolecular chelation to the pyranose ring-oxygen to form a syn chairboat structure was shown to be a useful method for the preparation of manno-β-C-glycosides.
Abstract: 2‘-Aldehydes and 2‘-ketones of α-C-glycosides, including the gluco-, galacto-, and manno- series, were epimerized exclusively to their β-anomers in good-to-excellent yields under basic conditions and in the presence of zinc acetate. The β-stereoselectivity is independent of the neighboring group at 2-O-substitution of sugar substrates. Therefore, this provides a particularly useful method for the preparation of manno-β-C-glycosides. The epimerization is likely initiated by the formation of Zn-enolate that is stabilized by intramolecular chelation to the pyranose ring-oxygen to form a syn chair-boat structure. Due to the activation generated by the Zn−O coordination, fission of the C1−O bond occurs, leading to opening of the pyranose ring, which is spontaneously followed by a change in conformation. The more stable anti chair-boat transition state is favored, and the subsequent hetero-intramolecular Michael addition results in the formation of β-C-glycoside in a ring-closure step.
47 citations
TL;DR: Preliminary studies indicate that each epimer causes time-dependent inactivation of S-adenosyl-L-homocysteine hydrolase, however each presented distinct kinetic characteristics.
38 citations
TL;DR: The first enantiospecific synthesis of phospholipase A2 (PLA2) inhibitor (-)-cinatrin B (2) from the D-arabinose derivative 9 is described.
Abstract: The first enantiospecific synthesis of phospholipase A2 (PLA2) inhibitor (−)-cinatrin B (2) from the d-arabinose derivative 9 is described. The spirolactone system was formed by an Ireland−Claisen rearrangement of the allyl ester 8 followed by hydrolysis and stereoselective iodolactonization. The stereoselectivity of the rearrangement was controlled by the asymmetry in the allylic alcohol fragment. Ester (S)-8 gave the desired rearrangement product 7 and the epimer 13 in high yield as a 73:27 ratio, respectively. The final stereocenter at C2 was introduced via a chelation-controlled addition of the Grignard reagent derived from trimethylsilylacetylene to α-hydroxy ketone 6. Transformation of the terminal alkyne into the methyl ester 21 followed by acetal hydrolysis and selective lactol oxidation afforded cinatrin B methyl ester (22). Base hydrolysis and acid-induced relactonization then gave (−)-cinatrin B (2).
38 citations
TL;DR: The target compound (+)-1 and its epimer 15 were readily obtained from 1,5-diallyl-2-pyrrolidinones 2b and 7b, respectively, via ring-closing metathesis, amide group reduction, and CC-double bond hydrogenation as mentioned in this paper.
36 citations
TL;DR: It is shown that high molecular complexity of conformationally constrained bicyclic systems is not a requirement to achieve highly selective and potent group 2 mGluRs agonists.
Abstract: The asymmetric synthesis and biological activity of (2S,1‘S,2‘S,3‘R)-2-(2‘-carboxy-3‘-methylcyclopropyl) glycine 7 and its epimer at the C3‘ center 6 are described. Compound 7 is a highly potent an...
33 citations
TL;DR: A new sesquiterpene lactone was isolated with known dihydrochrysanolide derivatives from the flowers of Chrysanthemum coronarium L., and their structures were identified by spectroscopic data.
Abstract: A new sesquiterpene lactone (1) was isolated with known dihydrochrysanolide derivatives (2 and 3) from the flowers of Chrysanthemum coronarium L., and their structures were identified by spectroscopic data. The stereochemistry of the epimers (1 and 2) was determined from NOESY data and an X-ray crystallographic analysis. The isolated compounds (1–3) were examined for their cytotoxic activity against such human cell lines as A549, PC-3 and HCT-15.
20 citations
TL;DR: In this paper, tetrose isomerization and C-2 epimerization by the industrially important d -xylose ketol-isomerase (E.C.5) with both the d and l -forms of the sugars were described.
Abstract: We describe novel tetrose isomerizations and C-2 epimerizations by the industrially important d -xylose ketol-isomerase (E.C.5.3.1.5) with both the d - and l -forms of the sugars. We further show that in addition to isomerization to d -fructose, d -glucose is slowly C-2 epimerized to d -mannose. The formation rate of the C-2 epimer was 0.03 mg mg m 1 min m 1 from d -glucose, 0.56 mg mg m 1 min m 1 from d -arabinose and 3.0 mg mg m 1 min m 1 from d -erythrose. The equilibria of the reaction products as a function of temperature were measured for threose/erythrulose/erythrose, arabinose/ribulose/ ribose and glucose/fructose/mannose.
18 citations
TL;DR: A concise enantioselective synthesis of 2,5-imino-2,5,6-trideoxy-d -manno-heptitol (6deoxy-homoDMDP) was achieved by.
Abstract: A concise enantioselective synthesis of 2,5-imino-2,5,6-trideoxy- d -manno-heptitol (6-deoxy-homoDMDP) and 2,5-imino-2,5,6-trideoxy- l -gulo-heptitol has been achieved. These compounds were used as stereochemical references to establish the absolute configuration of the corresponding naturally occurring stereoisomers, recently isolated from Hyacinthus orientalis.
16 citations
TL;DR: In this article, a stereoselective synthesis of the miharamycin sugar moiety epimer at C-3′ was accomplished in high yield starting from an appropriate (Z)-Wittig product, synthesized by Wittig reaction of a 4,6-O-benzylidene protected hexopyranosid-3-ulose with [(ethoxycarbonyl)methylene]triphenylphosphorane followed by iodine promoted isomerisation of the (E)-WITTIG product formed.
15 citations
TL;DR: A new convergent synthesis of the antitumor steroid formestane (4-OHA) 5 has been performed from the easily available epimeric mixture of 5 alpha- and 5 beta-androst-3-en-17-one 1a and 1b in order to attempt a yield improvement.
TL;DR: A REDOR NMR study was performed on the two epimeric covalent hydrates A and B of 6,7-bis(trifluoromethyl)-8-D-ribityllumazine to confirm the stereochemical assignments previously based solely on results for epimer B.
Abstract: The two epimeric covalent hydrates A and B of 6,7-bis(trifluoromethyl)-8-D-ribityllumazine are metabolically stable analogues of hypothetical intermediates proposed in the reactions catalyzed by riboflavin synthase and lumazine synthase. To confirm the stereochemical assignments previously based solely on results for epimer B, a 15 N{ 19 F} REDOR NMR study was performed on the complex formed from epimer A and a recombinant, uniformly 15 N-labeled F22W mutant of Bacillus subtilis lumazine synthase. The results indicate that the fluorines of the ligands are closer to the side chain nitrogens of Arg127 and farther away from the side chain nitrogens of Lys135 in epimer B than in epimer A. These results are consistent with the assignment of the earlier 7R configuration of epimer A and the 7S configuration of epimer B.
TL;DR: In this article, a deterministic synthesis of 12-oxo-PDA starting with (1 R,3 S )-cyclopenten-1,3-diol monoacetate is accomplished.
TL;DR: In this article, the total assignment of the incomplete stereostructure of a new squalene-derived epoxy tri-tetrahydrofuran (THF) diol to the structural formula 3 has been achieved through the first asymmetric syntheses of (22 S )- 3 and its epimer (22 R )- 4.
TL;DR: An efficient and stereoselective synthetic route has been developed to both noviose and its C-(4) epimer, thus providing a platform for the investigation of the structure–activity relationships (SAR) involving the methoxy group ofNoviose.
TL;DR: The tendencies experienced previously in the tryptamine and dopamine series were observed also in the histamine series; that is, at C-1, the R configuration is favored over the S one, and lactamization is faster in the former than in the latter case.
Abstract: The reaction of secologanin (1) (mainly in its tetraacetylated form 1a) with histamine (2) and its benzyl derivative (2b) was investigated. With the benzylated amine (2b), the main product was the normal, tetraacetylated benzyl derivative of histeloside having the R configuration at the new center of chirality, C-1 (5b), with a small amount of an unidentified minor component (probably the 1S epimer 5a). In a slightly acidic medium, the reaction with histamine (2) gave two products in an approximately 6:4 ratio. The main compound proved to be the normal, tetraacetylated derivative of the lactam histelosamide with R configuration at C-1 (7b), and the minor product was the tetraacetylisohisteloside with S configuration at the same C-1 center (3a). When the reaction was carried out under acid-free conditions, in addition to the epimeric pair of the normal tetraacetylated lactam (7a, 7b) and the tetraacetylisohisteloside with 1S configuration (3a), tetraacetylneohistelosamide (8b) was also isolated, in which t...
TL;DR: The synthesis of a lyngbyastatin 1-Ibu-epilyngbyastsatin 1 mixture combined with NMR and molecular modeling studies proved that natural lyng byastatin 2 was only one Ibu epimer rather than a mixture of both and that the configuration of this epimer in the Ibu unit was R.
Abstract: The synthesis of a lyngbyastatin 1-Ibu-epilyngbyastatin 1 mixture combined with NMR and molecular modeling studies proved that natural lyngbyastatin 1 was only one Ibu epimer rather than a mixture of both and that the configuration of this epimer in the Ibu unit was R. The substance isolated with lyngbyastatin 1 was Ibu-epidolastatin 12. The extreme broadness in the proton NMR spectra of lyngbyastatin 1 and Ibu-epidolastatin 12 was exchange broadening due to rotation about the Ibu-Ala amide bond. It was a consequence of (1) a small energy difference between the cis and trans forms of this bond, (2) a substantial difference in conformation between these forms, and (3) a lowered barrier between them compared to most amide bonds (due to steric hindrance). The synthetic lyngbyastatin 1-Ibu-epilyngbyastatin 1 mixture had significant activities against cancer cells and in stimulating actin polymerization, but was less active than dolastatin 11 in all assays.
TL;DR: In this article, a chiral HPLC analysis of the key β-hydroxy ester intermediates in these syntheses revealed that appreciable levels of racemisation had occurred in the aldol and Claisen condensation reactions used in this synthetic sequence.
Abstract: The syntheses of (2R,3S)-2-tert-butyldiphenylsilyloxymethylpyrrolidin-3-ol (TBDPS-protected CYB-3) (21) and its C(3) epimer (25) have been achieved in 9 and 8 steps respectively from D-serine. However, chiral HPLC analysis of the key β-hydroxy ester intermediates in these syntheses (17 and 18) revealed that appreciable levels of racemisation had occurred in the aldol and Claisen condensation reactions used in this synthetic sequence.
TL;DR: 3-demethylhimbacine (3-norhimbACine) 2, bearing an absolute configuration corresponding to that of 1, was found to show more potent muscarinic M(2) subtype receptor binding activity than natural 1.
TL;DR: Starting with (±)-7α-hydroxy-6β-hydroxymethyl-2-oxa-cis-bicyclo[3.3.0] octan-3-one 15α,β-19-carboxy-20-norprostaglandins Fα were synthesized as discussed by the authors.
Abstract: Starting with (±)-7α-hydroxy-6β-hydroxymethyl-2-oxa-cis-bicyclo[3.3.0]octan-3-one 15α,β-19-carboxy-20-norprostaglandins Fα were synthesized.
TL;DR: In this paper, the formation of Zn-enolate that is stabilized by intramolecular chelation to the pyranose ring-oxygen to form a syn chairboat structure was shown to be a useful method for the preparation of manno-β-C-glycosides.
Abstract: 2‘-Aldehydes and 2‘-ketones of α-C-glycosides, including the gluco-, galacto-, and manno- series, were epimerized exclusively to their β-anomers in good-to-excellent yields under basic conditions and in the presence of zinc acetate. The β-stereoselectivity is independent of the neighboring group at 2-O-substitution of sugar substrates. Therefore, this provides a particularly useful method for the preparation of manno-β-C-glycosides. The epimerization is likely initiated by the formation of Zn-enolate that is stabilized by intramolecular chelation to the pyranose ring-oxygen to form a syn chair-boat structure. Due to the activation generated by the Zn−O coordination, fission of the C1−O bond occurs, leading to opening of the pyranose ring, which is spontaneously followed by a change in conformation. The more stable anti chair-boat transition state is favored, and the subsequent hetero-intramolecular Michael addition results in the formation of β-C-glycoside in a ring-closure step.
Patent•
08 Mar 2002
TL;DR: In this paper, a series of processes are continuously executed which comprises (i) an isomerization process in which a fraction of alkyl jasmonate with epimer concentration =20% and (iii) a process where thin-film evaporation treatment is applied to the crude fraction having high epimer concentrations obtained in the process (ii) and a fraction containing impurity of high boiling point is continuously eliminated.
Abstract: PROBLEM TO BE SOLVED: To provide a method of manufacturing continuously and efficiently alkyl jasmonate with epimer concentration >=20% from alkyl jasmonate having low epimer concentration which comes from alkyl jasmonate distillation purification process. SOLUTION: A series of processes are continuously executed which comprises (i) an isomerization process in which a fraction of alkyl jasmonate with epimer concentration =20% and (iii) a process in which thin-film evaporation treatment is applied to the crude fraction having high epimer concentration obtained in the process (ii) and a fraction containing impurity of high boiling point is continuously eliminated.
01 Nov 2002
TL;DR: N3-protection improved the stereoselectivity in the ring-opening reaction and gave N3-benzyloxymethyl (BOM)-1',2'-epoxy nucleoside 11 obtained from 10 gave the target 12 as the sole product.
Abstract: Dimethyldioxirane-mediated epoxidation of 3',5'0-(
TL;DR: In this article, a phosphonic acid analogue of S-adenosyl-L-homocysteine was prepared by a novel method and the epimeric mixture separated.
Abstract: A phosphonic acid analogue of S-adenosyl-L-homocysteine was prepared by a novel method and the epimeric mixture separated. Preliminary studies indicate that each epimer causes time-dependent inactivation of S-adenosyl-L-homocysteine hydrolase, however each presented distinct kinetic characteristics.
TL;DR: In this article, the bromobenzene-derived and enantiopure cis-1,2-dihydrocatechol 3 has been converted, via a reaction sequence involving Diels-Alder cycloaddition, anionic oxy-Cope rearrangement and Wolff ring-contraction steps, into compound 4 and epimer 24, which embody key structural elements associated with the nonadride-type natural products CP-225,917 (1) and CP-263,114 (2).
Abstract: The bromobenzene-derived and enantiopure cis-1,2-dihydrocatechol 3 has been converted, via a reaction sequence involving Diels–Alder cycloaddition, anionic oxy-Cope rearrangement and Wolff ring-contraction steps, into compound 4 and epimer 24, which embody key structural elements associated with the nonadride-type natural products CP-225,917 (1) and CP-263,114 (2).
TL;DR: In this paper, the absolute configuration of natural product (-)-hyrtiosal has been determined, and its C-16 epimer has been prepared from sclareol in moderate yield.
Abstract: (-)-Hyrtiosal and its C-16 epimer have been prepared from sclareol in moderate yield. The absolute configuration of natural product (-)-hyrtiosal has being determined.
28 Apr 2002
TL;DR: 2'-Aldehydes and 2'-ketones of alpha-C-glycosides, including the gluco-, galacto-, and manno- series, were epimerized exclusively to their beta-anomers in good-to-excellent yields under basic conditions and in the presence of zinc acetate.
Abstract: 2'-Aldehydes and 2'-ketones of alpha-C-glycosides, including the gluco-, galacto-, and manno- series, were epimerized exclusively to their beta-anomers in good-to-excellent yields under basic conditions and in the presence of zinc acetate. The beta-stereoselectivity is independent of the neighboring group at 2-O-substitution of sugar substrates. Therefore, this provides a particularly useful method for the preparation of manno-beta-C-glycosides. The epimerization is likely initiated by the formation of Zn-enolate that is stabilized by intramolecular chelation to the pyranose ring-oxygen to form a syn chair-boat structure. Due to the activation generated by the Zn-O coordination, fission of the C1-O bond occurs, leading to opening of the pyranose ring, which is spontaneously followed by a change in conformation. The more stable anti chair-boat transition state is favored, and the subsequent hetero-intramolecular Michael addition results in the formation of beta-C-glycoside in a ring-closure step.
TL;DR: The first enantiospecific synthesis of PL2 inhibitor (−)-cinatrin B (2) from the d-arabinose derivative was described in this article, where the spirolactone system was formed by an Ireland−Claisen rearrangement of the allyl ester 8 followed by hydrolysis and stereoselective iodolactonization.
Abstract: The first enantiospecific synthesis of phospholipase A2 (PLA2) inhibitor (−)-cinatrin B (2) from the d-arabinose derivative 9 is described. The spirolactone system was formed by an Ireland−Claisen rearrangement of the allyl ester 8 followed by hydrolysis and stereoselective iodolactonization. The stereoselectivity of the rearrangement was controlled by the asymmetry in the allylic alcohol fragment. Ester (S)-8 gave the desired rearrangement product 7 and the epimer 13 in high yield as a 73:27 ratio, respectively. The final stereocenter at C2 was introduced via a chelation-controlled addition of the Grignard reagent derived from trimethylsilylacetylene to α-hydroxy ketone 6. Transformation of the terminal alkyne into the methyl ester 21 followed by acetal hydrolysis and selective lactol oxidation afforded cinatrin B methyl ester (22). Base hydrolysis and acid-induced relactonization then gave (−)-cinatrin B (2).
TL;DR: The asymmetric, stereocontrolled total syntheses of (+) and (−)-spirotryprostatin B (2) are described in this paper, where the core pyrrolidine ring was accomplished via a diastereoselective asymmetric [1, 3]-dipolar cycloaddition reaction.
Abstract: The asymmetric, stereocontrolled total syntheses of (+) and (−)-spirotryprostatin B ( 2 ) are described. Formation of the core pyrrolidine ring was accomplished via a diastereoselective asymmetric [1,3]-dipolar cycloaddition reaction. Addition of 3-methoxy-3-methylbutanal to (5R,6S)-2,3,5,6-tetrahydro-5,6-diphenyl-1,4-oxazin-2-one generated an azomethine ylide that reacted with ethyl oxindolylidene acetate to furnish the desired cycloadduct ( 11 ) that possessed the correct relative and absolute stereochemistry of natural spirotryprostatin B. The key dipolar cycloaddition reaction sets four contiguous stereogenic centers. Reductive cleavage of the oxazinone generated the spiro-oxindole pyrrolidine ( 19 ) that was coupled to d -proline benzyl ester and cyclized to the pentacyclic diketopiperazine 22 . A Barton-modified Hunsdiecker protocol effected oxidative decarboxylation to yield 12-epi-spirotryprostatin B ( 30 ). Thermodynamic epimerization of the d -proline stereogenic center with sodium methoxide yielded spirotryprostatin B as the major product. The antipode of the natural product, ent-spirotryprostatin B, was prepared from (5S,6R)-2,3,5,6-tetrahydro-5,6-diphenyl-1,4-oxazin-2-one. Several synthetic intermediates and spirotryprostatin analogs were tested for their activity as G2/M phase cell cycle inhibitors and microtuble assembly against 3Y1 and tsFT210 mammalian cells.