Showing papers on "Epimer published in 2012"
TL;DR: Development of a highly sensitive method for 3-epi-25(OH)D(3) measurement is described and the prevalence of this epimer in adult clinical serum specimens is established and it is found in the majority of human serum specimens.
Abstract: Context: Epimers have identical molecular structure but differ in stereochemical configuration. It is widely believed that the C-3 epimer of 25-hydroxyvitamin D3 [3-epi-25(OH)D3] is found only in neonates. However, this epimer was recently detected in a limited number of adults. The physiological importance of 3-epi-25(OH)D3 is uncertain but might affect 25-hydroxyvitamin D test results and thereby reliability of the 25-hydroxyvitamin D3 [25(OH)D3] measurement. Objective: This project describes development of a highly sensitive method for 3-epi-25(OH)D3 measurement and establishes the prevalence of this epimer in adult clinical serum specimens. Design, Setting, Participants, and Main Outcome Measure: Serum 25(OH)D3, 3-epi-25(OH)D3, and 25(OH)D2 concentrations were determined in a cohort of patients (n = 214; age neonate to 80+ yr). High-performance liquid chromatography with ultraviolet detection and high-performance liquid chromatography tandem mass spectrometry with atmospheric pressure chemical ionizat...
170 citations
TL;DR: Stereoselective oxylactonization of ortho-alkenylbenzoate with chiral hypervalent iodine is applied to the asymmetric synthesis of 4-oxyisochroman-1-one polyketide metabolites including 4-hydroxymellein.
79 citations
TL;DR: This study demonstrates that use of 2,4,6-trimethylpyridine as the base in peptide couplings produces glycopeptides with high efficiency and low epimerization, and demonstrates that this preference for the unnatural epimer over the natural epimer can be the major product in some reactions.
Abstract: Glycopeptides are extremely useful for basic research and clinical applications, but access to structurally defined glycopeptides is limited by the difficulties in synthesizing this class of compounds. In this study, we demonstrate that many common peptide coupling conditions used to prepare O-linked glycopeptides result in substantial amounts of epimerization at the α position. In fact, epimerization resulted in up to 80% of the non-natural epimer, indicating that it can be the major product in some reactions. Through a series of mechanistic studies, we demonstrate that the enhanced epimerization relative to nonglycosylated amino acids is due to a combination of factors, including a faster rate of epimerization, an energetic preference for the unnatural epimer over the natural epimer, and a slower overall rate of peptide coupling. In addition, we demonstrate that use of 2,4,6-trimethylpyridine (TMP) as the base in peptide couplings produces glycopeptides with high efficiency and low epimerization. The in...
58 citations
TL;DR: Various steroidal benzylidenes were synthetized from pregnenolone with benzaldehyde and p-substituted benzaldehydes, resulting in a mixture of two steroidal pyrazoline epimers which could be separated only in their acetylated form.
53 citations
TL;DR: A comparison of 20R isomer to its 20S counterpart in biological evaluation demonstrates that they have different behaviors in antiproliferative and metabolic studies.
Abstract: The non-naturally occurring 20R epimer of 20-hydroxyvitamin D3 is synthesized based on chemical design and hypothesis. The 20R isomer is separated by semipreparative HPLC, and its structure is characterized. A comparison of 20R isomer to its 20S counterpart in biological evaluation demonstrates that they have different behaviors in antiproliferative and metabolic studies.
27 citations
TL;DR: The synthesis of four candidate stereoisomers of cephalosporolide H is described, made possible by a zinc-chelation strategy for controlling the stereochemistry of oxygenated 5,5-spiroketals.
Abstract: The synthesis of four candidate stereoisomers of cephalosporolide H is described, made possible by a zinc-chelation strategy for controlling the stereochemistry of oxygenated 5,5-spiroketals. The same strategy likewise enables the first stereocontrolled synthesis of cephalosporolide E, which is typically isolated and prepared admixed with its spiroketal epimer, cephalosporolide F.
22 citations
TL;DR: The absolute configurations of onchidione, previously reported from the marine pulmonate Onchidium sp.
21 citations
TL;DR: The structure of 18,21-diisopropyl-geldanamycin hydroquinone was proven by its independent synthesis from the natural product and was shown to be generally applicable to the racemization-free conversion of several aldehydes into the respective α-chloroethyl ketone and to the coupling protocol.
Abstract: The title compounds were synthesized in a longest sequence of 27 linear steps and with an overall yield of 2.9 and 3.9?%. In the course of the synthesis, two aldehydes representing carbon fragments C1?C7 (Eastern fragment) and C9?C21 (Western fragment) were prepared from D-mannitol, each of which incorporated a key stereogenic center at the respective secondary methyl ether group (C6, C12) from the chiral pool material. The assembly of the two aldehydes was achieved employing a-chloroethyl magnesium chloride as a two-carbon building block. The carbenoid reagent was generated from a-chloroethyl para-tolylsulfoxide by sulfoxidemagnesium exchange and it added smoothly to the highly sensitive aldehyde of the Eastern fragment (C1?C7). Upon oxidation, an a-chloroethyl ketone was generated, which underwent a clean and high-yielding reductive SmI2-promoted addition to the other aldehyde fragment. Dehydration delivered the key double bond between C8 and C9 in an overall yield of 72?% over four steps. The method was shown to be generally applicable to the racemization-free conversion of several aldehydes into the respective a-chloroethyl ketone (11 examples, 6495?%) and to the coupling protocol (5 examples, 6690?%). The further course of the geldanamycin hydroquinone synthesis included a diastereoselective reduction at C7 and the implementation of the amino group at C20. Since deprotection of the two isopropyl protecting groups could not be achieved in significant yields, the structure of 18,21-diisopropyl-geldanamycin hydroquinone was proven by its independent synthesis from the natural product.
16 citations
TL;DR: The total syntheses of the 3,6-dihydroxydecanolide from Cordyceps militaris and the novel C-3 epimer are reported using a diastereoselective Nozaki-Hiyama-Kishi reaction in the key cyclization to generate the 6R stereocenter.
16 citations
TL;DR: A flexible synthesis of the C1-C12 fragment of Tedanolide C has been accomplished in eight steps from 2-methyl-2,4-pentadienal.
16 citations
TL;DR: Putaminoxin E, a natural nonanolide, and its C-9 epimer were synthesized for the first time starting from pentane-1,5-diol and butyraldehyde.
TL;DR: A new secoiridoid and its known epimer olenoside B, were isolated from olive mill wastewater as a mixture of two isomers by spectroscopic methods including 2-D NMR.
TL;DR: In this paper, the synthesis of polyalthenol from ent-halimic acid as starting material has been carried out and the structure of the natural product has been confirmed in this way, and the synthesized indole sesquiterpenes 10 and 11 and their acetylderivatives 32 and 33 inhibited cellular proliferation of human leukaemic and solid tumour cell lines.
TL;DR: A stereoselective synthesis of the C20-C32 tetrahydropyran core of the phorboxazoles has been achieved in only seven steps and in a 31% overall yield.
TL;DR: The tin(iv) bromide promoted reaction of 7-hydroxy-7-phenylhept-2-enyl(tributyl)stannane 11 with benzaldehyde gave a mixture of the epimeric 1,8-diphenyloct-3-ene-1, 8-diols 12 and so indirect methods were developed for aliphatic 1,7-stereocontrol to complete diastereoselective syntheses of
Abstract: The tin(IV) bromide promoted reaction of 7-hydroxy-7-phenylhept-2-enyl(tributyl)stannane 11 with benzaldehyde gave a mixture of the epimeric 1,8-diphenyloct-3-ene-1,8-diols 12 and so indirect methods were developed for aliphatic 1,8-stereocontrol to complete diastereoselective syntheses of (±)-patulolide C 1 and (±)-epipatulolide C 40. (5Z)-3,7-syn-7-(2-Trimethylsilylethoxy)methoxyocta-1,5-dien-3-ol 17 was prepared from the tin(IV) chloride promoted reaction of 4-(2-trimethylsilylethoxy)methoxypent-2-enyl(tributyl)stannane 16 with acrolein (1,5-syn : 1,5-anti = 96 : 4). An Ireland–Claisen rearrangement of the corresponding benzoyloxyacetate 21 with in situ esterification of the resulting acid using trimethylsilyldiazomethane gave methyl (4E,7Z)-2,9-anti-2-benzyloxy-9-(2-trimethylsilylethoxy)methoxydeca-4,7-dienoate 22 together with 10–15% of its 2,9-syn-epimer 26, the 2,9-syn- : 2,9-anti-ratio depending on the conditions used. An 88 : 12 mixture of esters was taken through to the tert-butyldiphenylsilyl ether 38 of (±)-patulolide C 1 together with 6% of its epimer 39, by reduction, a Wittig homologation and deprotection/macrocyclisation. Following separation of the epimeric silyl ethers, deprotection of the major epimer 38 gave (±)-patulolide C 1. The success of 2,3-Wittig rearrangements of allyl ethers prepared from (5Z)-3,7-syn-7-(2-trimethylsilylethoxy)methoxyocta-1,5-dien-3-ol 17 was dependent on the substituents on the allyl ether. Best results were obtained using the pentadienyl ether 56 and the cinnamyl ether 49 that rearranged with >90 : 10 stereoselectivity in favour of (1E,5E,8Z)-3,10-syn-1-phenyl-10-(2-trimethylsilylethoxy)methoxyundeca-1,5,8-trien-3-ol 50. This product was taken through to the separable silyl ethers 38 and 39, ratio 7 : 93 by regioselective epoxidation and alkene reduction using diimide, followed by deoxygenation, ozonolysis, a Wittig homologation and selective deprotection/macrocyclisation. Deprotection of the major epimer 39 gave (±)-epipatulolide C 40.
TL;DR: The spatial orientation of the hydroxyl moiety in 3b, 4b, 2a, and 2b is proposed to be the structural requirement for high μ-opioid receptor binding affinity and their agonist or antagonist activity.
TL;DR: A profile of impurities in bortezomib anhydride, produced by a recently developed convergent technology, has been characterized and two epimeric products of oxidative degradation of boron are revealed.
Abstract: A profile of impurities in bortezomib anhydride, produced by a recently developed convergent technology, has been characterized. HPLC-MS analysis of the drug essence revealed three impurities: an epimer of bortezomib, resulting from partial racemization of l-phenylalanine's stereogenic center during the chemical synthesis, and two epimeric products of oxidative degradation of bortezomib, in which boron is replaced by the OH group. The impurities were obtained by chemical synthesis and characterized by physical methods.
TL;DR: In this article, the potential of vibrational circular dichroism (VCD) for discerning between pairs of epimers or inverse epimmers was considered in principle for the alnumycin A1 pair and the C-1 epimer of A1α ( ent -A1β) by DFT-calculated spectra obtained at the M06-2X/6-31G(d) level of theory.
01 Jan 2012
TL;DR: In this paper, Eupatorium lasiophthalmum yielded fourteen sesquiterpene lactones (1-14) including one new epimer (7) and a revision of the reported stereochemistry of 2 is suggested.
Abstract: An investigation of Eupatorium lasiophthalmum yielded fourteen sesquiterpene lactones (1-14) including one new epimer (7) and a revision of the reported stereochemistry of 2 is suggested. One known sesquiterpene (15) and one triterpene (16) with a novel skeleton were found. Two known flavonoids (17-18) were also isolated. Michael adducts were prepared out of 1, 4 and 5 and their reversibility studied. The isolates 1-5, 7, 9, 15 and a cysteine ester adduct (19) were subjected to biological test to determine cytotoxicity against five different breast cancer cell lines. The adduct 19 showed significantly less cytotoxic efficacy compared to the sesquiterpene lactones. The anti-inflammatory activity of 4 was evaluated on LPS stimulated human monocytes.
Patent•
27 Dec 2012
TL;DR: In this article, a histone deacetylase inhibitor named ZYJ-D08a and its epimer named ZyJD08ae were described as histone-deacetylases inhibitors in pharmacy field and their preparative methods and medical use for inhibiting tumor.
Abstract: The present invention discloses ZYJ-D08a and its epimer ZYJ-D08ae as histone deacetylase inhibitors in pharmacy field, and their preparative methods and medical use for inhibiting tumor. ZYJ-D08a and its epimer ZYJ-D08ae are represented by formula (I).
TL;DR: The 4'-epimer of 2-fluoronoraristeromycin was synthesized by employing bis-t-butoxycarbonyl (Boc) protected 2- fluoroadenine as a superior substrate for the Mitsunobu reaction with the appropriate cyclopentenol.
TL;DR: In this paper, an enantioselective total synthesis of (−)-FR182877 is described, which includes the ABCD ring system of (−−)-FR2877 with the correct seven stereogenic centers.
Abstract: An enantioselective total synthesis of (−)-FR182877 is described. This total synthesis features 1) the one-pot stereoselective tandem IMDA-IMHDA reaction which affords the tetracyclic compound including the ABCD ring system of (−)-FR182877 with the correct new seven stereogenic centers, 2) the palladium-mediated 7-exo-trig intramolecular Heck reaction for the construction of the highly strained seven-membered F-ring, and 3) the iridium-mediated isomerization of the allylic alcohol to the α-methyl ketone followed by epimerization and the stereoselective reduction to furnish all the stereogenic centers of (−)-FR182877.
Patent•
05 Dec 2012
TL;DR: In this article, a preparation method and medical application to an anti-tumor aspect of a histone deacetylase inhibitor ZYJ-D08a and an epimer ZyJ-d08ae thereof in the technical field of drugs is described.
Abstract: The invention discloses a preparation method and medical application to an anti-tumor aspect of a histone deacetylase inhibitor ZYJ-D08a and an epimer ZYJ-D08ae thereof in the technical field of drugs. The histone deacetylase inhibitor ZYJ-D08a and the epimer ZYJ-D08ae thereof have a structure shown as a formula (I).