1,721,279 research outputs found
Stereoselective Synthesis of Optically Pure gamma-Fluoro-beta-Enaminosulfoxides and Reduction to gamma-Fluoro-beta-Aminosulfoxides
No full textThe aza-Wittig reaction of phospha&5-azenes with optically pure y-fluorosubstituted I~-
ketosulfoxides leads to the corresponding 13-enaminosulfoxides, which were easily isolated in
diastereomerically pure form. The stercoselective reduction of the enamine 3cb afforded the optically
pure [~-sulphinyl-amine5 cb in high overall yield
Synthesis and biological activity of b-fluoroalkyl b-amino alcohols
No full textThis paper reviews the synthesis of unnatural chiral b- ̄uoroalkyl b-amino alcohols, with an emphasis on their biological activity and
pharmaceutical application
Mass spectrometric investigation of some α-trifluoromethyl-α-amino acids
No full textThe fast atom bombardment-induced mass spectrometric behaviour of four fluorinated α-amino acids was studied in detail with the aid of metastable ion studies and accurate mass measurements. Comparison with the behaviour of unfluorinated analogues suggests that the presence of fluorine makes the carbonylic oxygen the most prone to protonation. This hypothesis was confirmed by AM1 semiempirical calculations which indicate that the carbonylic oxygen of the carboxyl group exhibits, in the case of fluorinated compounds only, the highest proton affinity
(R)-Trifluoro- and Difluoropyruvaldehyde N,S-Ketals: Chiral Synthetic Equivalents of alpha-Trifluoro and alpha-Difluoro alpha-Amino Aldehydes
No full textA new, efficient, and stereoselective two-step approach to stereochemically defined chiral nonracemic
ç-tri- and ç-difluoro â-amino alcohols (70% to >95% ee) is described, using tri- and difluoropyruvaldehyde
N,S-ketals (R)-1a,b as starting materials. Addition of Grignard reagents to (R)-1
occurs with moderate to excellent anti-stereocontrol, depending on the nature of the organomagnesium
halides, providing the â-p-tolylthio â-benzyloxycarbonylamino secondary carbinols 5.
The stereochemical outcome of these reactions can be rationalized by means of a chelated Cram’s
cyclic model, where the NCbz group is the chelating ligand and the p-tolylthio residue acts as the
stereocontrolling “large” group. Reductive displacement of the 2-p-tolylthio substituent of 5
efficiently takes places by means of the NaBH4/pyridine system, probably via the corresponding
intermediate transient imines 13, providing sulfur-free ç-tri- and ç-difluorinated â-amino alcohols
7 with high levels of anti-stereoselectivity. A considerable shift toward syn-stereoselectivity was
obtained performing the reaction on the corresponding phenylacetates 8. Cleavage and reduction
of the NHCbz moiety of 7 provided tri- and difluoro analogues of, respectively, norephedrine (11)
and ephedrine (12)
Probing the PI3K/Akt/mTor pathway using 31P-NMR spectroscopy : routes to glycogen synthase kinase 3
Full text linkProfessor Matteo Zanda and Professor Marcel Jaspars are gratefully acknowledged for the use of the NMR system and Russell Gray for running some of the NMR samples.Peer reviewe
Stereoselective Total Synthesis of Enantiomerically Pure 1-Trifluoromethyl Tetrahydroisoquinoline Alkaloids
No full textEnantiomerically pure 1-trifluoromethyl-tetrahydroisoquino- fluoro-â-iminosulfoxide (R)-3, and subsequent elaborations
line alkaloid analogues, in which C-1 is a quaternary stereo- of the sulfinyl auxiliary. The absolute stereochemistry of the
genic centre, have been synthesized by stereoselective intra- stereogenic centre was determined by X-ray diffraction on
molecular Pictet-Spengler reaction of the N-arylethyl ã-tri- the á-phenylpropionic ester (1R,29S)-1
gem-Difluoro-cyclohexene and -cycloheptene derivatives through cyclization of gem-difluoroallyl radicals
No full text6-Alkoxy-7-chloro-7,7-difluoro-5- [ (S)-(4-methylphenyl)sulfinyl]-I $heptadieneshave been transformed, through chlorine atom abstraction
by tributyltin radical, into the corresponding difluoroallyl radicals, which, via intramolecular trapping by the vinyl group and reduction
of the cyclohexenylmethyl and cycloheptenyl radicals obtained, gave gem-difluoro-cyclohexene and -cycloheptene derivatives. Reduction of
the intermediate difluoroallyl radical afforded the corresponding dechlorinated open-chain difluoro compounds as side-products
Unusual Trifluoroacetic Anhydride Promoted Fragmentation of a g,g,g-Trifluoro-b-(p-methoxyphenylamino) Sulfoxide
No full textThe reaction of a g,g,g-trifluoro-b-(p-methoxyphenylamino) sulfoxide with trifluoroacetic anhydride under Pummerer
conditions occurs in an abnormal fashion, providing an excellent yield of the cyclic six-membered sulfonium salt arising
from intramolecular interception of the usual trifluoroacetoxy-sulfonium intermediate by the electron rich p-methoxyphenyl group
NESS002ie: A new fluorinated thiol endopeptidase inhibitor with antinociceptive activity in an animal model of persistent pain
No full textor the past few decades membrane zinc metallopeptidases have been identified as important therapeutic targets in the control of pain. In particular, neutral endopeptidase (NEP) has been shown to play critical roles in the metabolism of the endogenous peptides Met- and Leu-enkephalins. In this study, we have evaluated the activity of a new fluorinated peptidase inhibitor NESS002ie in both in vitro and in vivo assays. NESS002ie has been compared to the peptidomimetic compound thiorphan and the previously reported NEP selective thiol inhibitor C20. The metallopeptidases inhibitory activity of NESS002ie was tested in vitro using a highly, sensitive, continuous, fluorometric, enzyme assay. Also, the analgesic propriety of NESS002ie, thiorphan and C20 have been evaluated in vivo, by intraplantar, intravenous and intrathecal administration, through nociception assays based on formalin test in mice. Metallopeptidases assays have shown an inhibitory potency of NESS002ie in the nanomolar range for NEP and angiotensin-converting enzyme (ACE). The new fluorinated inhibitor showed higher analgesic activity and bioavailability compared to thiorphan and C20 when administered by both intravenous and intrathecal injections. More significantly, intrathecal injection of NESS002ie reduced both the first and the second phases of the formalin biphasic pain response. In addition, naltrindole and naloxone reversed the analgesic effect of NESS002ie with a diverse profile. This study shows an improvement in relief of inflammation and pain, in vivo, using NESS002ie compared to reference compounds thiorphan and C20. This significant effect could be due to the replacement of isobutyl chain of the thiol C20 with the trifluoromethyl group
Synthesis of N-Cbz-fluoropyruvaldehyde N,S-ketals: construction of highly stereoselective and high yielding synthetic reactions using multivariate modelling and design
No full textThe synthesis of (R)-fluoropyruvaldehyde-N,S-ketals via a tandem
self-immolative Pummerer-type rearrangement of enantiopure (R)-ot-fluoroalkyl-13-
sulfinylenamines has been studied using statistical experimental design and multivariate
modelling. By this study a procedure has been established which simultaneously gives
excellent enantioselectivity and synthetically useful yields. The improvement of the ee of
the trifluoro derivative was from 69% to 82%. The optimised procedure has been scaled
up (10 fold) and extended to the corresponding difluoro and chlorodifluoro derivatives,
with similarly good results. The chemometric analysis, along with a crossover experiment,
strongly supports the hypothesis of a strictly intramolecular process, according to the
previously proposed mechanism
- …
