Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug.

ABSTRACT: Four enantiomerically pure stereoisomers of rosaprostol (1), an antiulcer drug, were efficiently synthesized from the enantiomers of 2-(dimethoxyphosphoryl)-3-hexylcyclopentanone (3) as chiral substrates. The latter were obtained by resolution of racemic 3 with (+)-(R)-1-(1-naphthyl)ethylamine. The conversion of (+)-3 into rosaprostol stereoisomer (-)-1a was accomplished in four steps in 56% overall yield. According to the same protocol, the second stereoisomer (+)-1c was obtained from (-)-3 in 55% overall yield. A slightly improved procedure of the last two steps of the transformation of (+)-3 into (-)-1a allowed an increase in the overall yield to 64%. The remaining two stereoisomers, (-)-1b and (+)-1d, were obtained from (-)-1a and (+)-1c in 71 and 68% yield, respectively, by a two-reaction sequence, in which a Mitsunobu inversion of configuration at C-5 was the key step.

SUBMITTER: Perlikowska W

PROVIDER: S-EPMC5082602 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug.

Perlikowska Wiesława W Żurawiński Remigiusz R Mikołajczyk Marian M

Beilstein journal of organic chemistry 20161021

Four enantiomerically pure stereoisomers of rosaprostol (1), an antiulcer drug, were efficiently synthesized from the enantiomers of 2-(dimethoxyphosphoryl)-3-hexylcyclopentanone (3) as chiral substrates. The latter were obtained by resolution of racemic 3 with (+)-(R)-1-(1-naphthyl)ethylamine. The conversion of (+)-3 into rosaprostol stereoisomer (-)-1a was accomplished in four steps in 56% overall yield. According to the same protocol, the second stere ...[more]

PMID: 27829932

Similar Datasets

Enantiomerically Pure Tetravalent Neptunium Amidinates: Synthesis and Characterization.

Project description:The synthesis of a tetravalent neptunium amidinate [NpCl((S)-PEBA)3 ] (1) ((S)-PEBA=(S,S)-N,N'-bis-(1-phenylethyl)-benzamidinate) is reported. This complex represents the first structurally characterized enantiopure transuranic compound. Reactivity studies with halide/pseudohalides yielding [NpX((S)-PEBA)3 ] (X=F (2), Br (3), N3 (4)) have shown that the chirality-at-metal is preserved for all compounds in the solid state. Furthermore, they represent an unprecedented example of a structurally characterized metal-organic Np complex featuring a Np-Br (3) bond. In addition, 4 is the only reported tetravalent transuranic azide. All compounds were additionally characterized in solution using para-magnetic NMR spectroscopy showing an expected C3 -symmetry at low temperatures.

| S-EPMC7497184 | biostudies-literature

Diastereoselective synthesis and biological evaluation of enantiomerically pure tricyclic indolines.

Project description:Tricyclic indolines are common in both natural products and synthetic chemical probes. In this study we demonstrated that enantiomerically pure tricyclic indolines can be prepared from an inexpensive commercially available chiral starting material, pyroglutamic acid. The synthesis features a highly diastereoselective gold-catalyzed cyclization of alkyne-tethered indoles and subsequent diastereoselective reductive ring-opening reaction. Using this approach, we synthesized analogs of our previously discovered tricyclic indoline probes that possess antibacterial and resistance-modifying activity. The biological activity against methicillin-resistant Staphylococcus aureus (MRSA) of these analogues was evaluated and reported. The synthetic approach reported may be leveraged in the future to prepare diastereopure chemical probes for the determination of biological targets for drug discovery.

| S-EPMC5518930 | biostudies-literature

New Enantiomerically Pure Alkylimido Mo-Based Complexes. Synthesis, Characterization, and Activity as Chiral Olefin Metathesis Catalysts.

Project description:Molybdenum olefin metathesis catalysts that contain aliphatic 1-phenylcyclohexylimido (NPhCy) and 2-phenyl-2-adamantylimido (NPhAd) groups and (S)-Biphen or (R)-Trip)(THF) ligands (Biphen = 3,3'-di-tert-butyl-5,5',6,6'-tetramethyl-1,1'-biphenyl-2,2'-diolate; Trip = 3,3'-bis(2,4,6-triisopropylphenyl)-2,2'-binaphtholate) have been prepared. Their catalytic activity and enantioselectivity in desymmetrization reactions such as ring-closing metathesis of amines and lactams and ring-opening/cross-metathesis of substituted norborneols with styrene were compared to the results obtained with the only known alkylimido catalyst Mo(NAd)(CHCMe(2)Ph)[(S)-Biphen]. The activities and enantioselectivities provided by these new chiral complexes vary significantly, but in virtually all instances explored were not superior to the adamantylimido analogs.

| S-EPMC2600727 | biostudies-literature

Enantiomerically Pure 5,13-Dicyano-9-oxa[7]helicene: Synthesis and Study.

Project description:Optically pure dicyano oxa[7]helicenes and helicene-like molecules have been prepared and investigated for their optical behavior. The isomers of the intermediate 4,4'-biphen-anthrene-3,3'-diol were resolved by physically separating their 1-menthyl carbonate derivatives. In this work a mild method was developed to cleave ArOMe in presence of a cyano group. The optical rotation of atropisomeric diol, helicenes-like compounds and the oxa[7]helicenes was observed to be in increasing order, while the molecules also showed good response to circularly polarized luminescence.

| S-EPMC6402497 | biostudies-literature

Synthesis of enantiomerically pure N-(2,3-dihydroxypropyl)arylamides via oxidative esterification.

Project description:A highly efficient synthesis of enantiomerically pure (S) and (R)-isomers of N-(2,3-dihydroxypropyl)arylamides has been developed with good overall yields in a two step process. The key step involves the ring opening of the chiral epoxide with a nitrogen heterocyclic carbene (NHC) and further rearrangement to chiral N-(2,3-dihydroxypropyl)arylamides in high yields and enantioselectivity. During the reaction, no erosion in chiral purity was observed.

| S-EPMC3817507 | biostudies-literature

Enantiomerically Pure Quinoline-Based ?-Opioid Receptor Agonists: Chemoenzymatic Synthesis and Pharmacological Evaluation.

Project description:Racemic K -opioid receptor (KOR) agonist 2-(3,4-dichlorophenyl)-1-[(4aRS,8SR,8aSR)-8-(pyrrolidin-1-yl)-3,4,4a,5,6,7,8,8a-octahydroquinolin-1(2H)-yl]ethan-1-one ((±)-4) was prepared in a diastereoselective synthesis. The first key step of the synthesis was the diastereoselective hydrogenation of the silyl ether of 1,2,3,4-tetrahydroquinoin-8-ol ((±)-9) to afford cis,cis-configured perhydroquinoline derivative (±)-10. Removal of the TBDMS protecting group led to a ?-aminoalcohol that reacted with SO2 Cl2 to form an oxathiazolidine. Nucleophilic substitution with pyrrolidine resulted in the desired cis,trans-configured perhydroquinoline upon inversion of the configuration. In order to obtain enantiomerically pure KOR agonists 4 (99.8?% ee) and ent-4 (99.0?% ee), 1,2,3,4-tetrahydroquinolin-8-ols (R)-8 (99.1?% ee) and (S)-8 (98.4?% ee) were resolved by an enantioselective acetylation catalyzed by Amano lipase PS-IM. The absolute configuration was determined by CD spectroscopy. The 4aR,8S,8aS-configured enantiomer 4 showed sub-nanomolar KOR affinity (Ki =0.81?nM), which is more than 200 times higher than the KOR affinity of its enantiomer ent-4. In the cAMP assay and the Tango ?-arrestin-2 recruitment assay, 4 behaved as a KOR agonist. Upon incubation of human macrophages, human dendritic cells, and mouse myeloid immune cells with 4, the number of cells expressing co-stimulatory receptor CD86 and proinflammatory cytokines interleukin 6 and tumor necrosis factor ? was significantly reduced; this indicates the strong anti-inflammatory activity of 4. The anti-inflammatory effects correlated well with the KOR affinity: (4aR,8S,8aS)-4 was slightly more potent than the racemic mixture (±)-4, and the distomer ent-4 was almost inactive.

| S-EPMC7496650 | biostudies-literature

Microbial Synthesis of the Forskolin Precursor Manoyl Oxide in an Enantiomerically Pure Form.

Project description:Forskolin is a promising medicinal compound belonging to a plethora of specialized plant metabolites that constitute a rich source of bioactive high-value compounds. A major obstacle for exploitation of plant metabolites is that they often are produced in small amounts and in plants difficult to cultivate. This may result in insufficient and unreliable supply leading to fluctuating and high sales prices. Hence, substantial efforts and resources have been invested in developing sustainable and reliable supply routes based on microbial cell factories. Here, we report microbial synthesis of (13R)-manoyl oxide, a proposed intermediate in the biosynthesis of forskolin and other medically important labdane-type terpenoids. Process optimization enabled synthesis of enantiomerically pure (13R)-manoyl oxide as the sole metabolite, providing a pure compound in just two steps with a yield of 10 mg/liter. The work presented here demonstrates the value of a standardized bioengineering pipeline and the large potential of microbial cell factories as sources for sustainable synthesis of complex biochemicals.

| S-EPMC4249197 | biostudies-literature

Synthesis of Enantiomerically Pure N-Boc-Protected 1,2,3-Triaminopropylphosphonates and 1,2-Diamino-3-Hydroxypropylphosphonates.

Project description:All possible isomers of 1,2,3-tri(N-tert-butoxycarbonylamino)propylphosphonate 6 were synthesized from the respective diethyl [N-(1-phenylethyl)]-1-benzylamino-2,3-epiiminopropylphosphonates 5 via opening the aziridine ring with trimethylsilyl azide (TMSN3) followed by hydrogenolysis in the presence of di-tert-butyl dicarbonate (Boc2O). [N-(1-phenylethyl)]-1-benzylamino-2,3-epiiminopropylphosphonates (1R,2R,1'S)-5a and (1S,2S,1'R)-5c were smoothly transformed into diethyl 3-acetoxy-1-benzylamino-2-[N-(1-phenylethyl)amino]propylphosphonates (1R,2R,1'S)-9a and (1S,2S,1'R)-9c, respectively by the opening of the aziridine ring with acetic acid. Transformations of [N-(1-phenylethyl)]-1-benzylamino-2,3-epiiminopropylphosphonates (1S,2R,1'S)-5b and (1R,2S,1'R)-5d into diethyl 3-acetoxy-1-benzylamino-2-[(1-phenylethyl)amino]propylphosphonates (1S,2R,1'S)-9b and (1R,2S,1'R)-9d were accompanied by the formation of ethyl {1-(N-benzylacetamido)-3-hydroxy-2-[(1-phenylethyl)amino]propyl}phosphonate (1S,2R,1'S)-10b and (1R,2S,1'R)-10d and 3-(N-benzylacetamido)-4-[N-(1-phenylethyl)]amino-1,2-oxaphospholane (3S,4R,1'S)-11b and (3R,4S,1'R)-11d as side products. Diethyl (1R,2R)-, (1S,2S)-, (1S,2R)- and (1R,2S)-3-acetoxy-1,2-di(N-tert-butoxycarbonylamino)propylphosphonates 7a-7d were obtained from the respective 3-acetoxy-1-benzylamino-2-[N-(1-phenylethyl)amino]propylphosphonates 9a-9d by hydrogenolysis in the presence of Boc2O.

| S-EPMC6864986 | biostudies-literature

Preparation of Enantiomerically Pure Perfluorobutanesulfinamide and Its Application to the Asymmetric Synthesis of ?-Amino Acids.

Project description:A high yielding and practical two-step synthesis of enantiomerically pure perfluorobutanesulfinamide from Senanayake's 2-aminoindanol-derived sulfinyl transfer reagent was developed and carried out on a multigram scale. Straightforward condensation of this sulfinamide with ethyl glyoxylate provided the N-perfluorobutanesulfinyl imino ester. The utility of this activated N-sulfinyl imino ester was demonstrated for reactions that gave either no product or very low yields with the corresponding less electrophilic N-tert-butanesulfinyl derivative. Specifically, the Rh(III)-catalyzed C-H bond addition of aromatic compounds to the N-perfluorobutanesulfinyl imino ester provided arylglycines with very high diastereoselectivities for a range of directing groups including pyrrolidine amide, azo, sulfoximine, 1-pyrazole, and 1,2,3-triazole functionalities. Thermal asymmetric aza-Diels-Alder reactions also proceeded in good yields and with high selectivity, including for the substituted dienes (E)-1,3-pentadiene and (2E,4E)-2,4-hexadiene.

| S-EPMC4761297 | biostudies-literature

Synthesis of enantiomerically pure D- and L-bicyclo[3.1.0]hexenyl carbanucleosides and their antiviral evaluation.

Project description:Based upon the fact that L-nucleosides have been generally known to be less cytotoxic than D-counterparts, L-bicyclo[3.1.0]hexenyl carbanucleoside derivatives with a fixed north conformation were designed and synthesized by employing a novel synthetic strategy starting from (R)-epichlorohydrin in order to search for new anti-HIV agents with high potency and less cytotoxicity. A tandem alkylation, ?-lactonization, a chemoselective reduction of ester in the presence of ?-lactone functional group, a RCM reaction, and a Mitsunobu coupling reaction were used as key reactions. D-Counterpart nucleosides were also prepared according to the same synthetic method. Among the synthesized carbanucleosides, D-thymine nucleoside, D-2 and L-thymine nucleoside, L-2 exhibited excellent anti-HIV-1 and -2 activities, in MT-4 cells, which were higher than those of ddI, an anti-AIDS drug. Whereas D-2 exhibited high cytotoxicity in MT-4 cell lines, L-2 did not show any discernible cytotoxicity in all cell lines tested, reflecting that L-2 may be a good candidate for an anti-AIDS drug. L-2 also showed weak anti-HSV-2 activity without cytotoxicity. However, none of the synthesized nucleosides exhibited antiviral activities against RNA viruses including coxsakie, influenza, corona and polio viruses, maybe due to their 2',3'-dideoxy structure. Potent antiviral effects of D-2 and L-2 indicate that nucleosides belonging to a class of D4Ns can be an excellent candidate for anti-DNA virus agents. This research strongly supports L-nucleosides of a class of D4Ns to be a very promising candidate for antiviral agents due to its low cytotoxicity and a good antiviral activity.

| S-EPMC7126181 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data