Synthesis of four diastereomeric enkephalins incorporating cyclopropyl phenylalanine

Four diastereomeric D-Ala2, Leu5-enkephalins have been synthesized and their CD spectra and rat brain binding affinities determined. Only the peptides containing Z-cyclopropyl phenylalanine residues showed strong binding affinity. No correlation between CD spectra and bioactivity could be made.     

Synthesis and NMR characterization of diastereomeric CPSMeG derivatives

Synthesis and stereochemical characterization of enantiomerically pure CPSMeG derivatives by NMR methods are reported. The effect of 5'-dimethoxytrityl on the conformational properties is described. It was found that in P-diastereomers the conformational differences about the C3'-O3' bond, as discernible from the delta J values, are enhanced by the presence of this protecting group.     

Synthesis of heteroaromatic analogues of prostaglandins

Synthesis of some thiazole and oxazole analogues of prostaglandins is reported.     

Synthesis and stereochemical characterization of diastereomeric nucleoside-phosphorothioselenoates by NMR methods

Synthesis and stereochemical characterization of enantiomerically pure nucleoside-phosphorothioselenoates are reported. The effects of solvent and temperature on the vicinal carbon-phosphorus couplings are described and the results are interpreted in terms of conformational changes influenced by stacking interactions between the bases and the phenyl rings.     

Synthesis and biological activity of modified amino prostaglandins

The synthesis of 15-hydroxy-15-methyl-9-oxo-prostanoic acid derivatives containing a C₂₀-dimethylamino group as well as the synthesis of 1-methyl-3-{6-[2-(3-hydroxy-3-methyl-octyl)-5-oxocyclopentyl]-n-hexyl}-thiourea are herein described.     

Synthesis of ring halogenated prostaglandins (1)

The synthesis of nine mono- and difluoro prostaglandins , , , , , , and , and two monochloro prostaglandins and , from appropriately protected derivatives of natural PGF₂ is described.     

Synthesis of isomeric 11-hydroxy 11-methyl prostaglandins

The synthesis of several novel 11-substituted prostaglandins has been achieved from PGA₂ methyl ester from the marine coral . The configuration of the substituents at position 11 is based on the nuclear magnetic resonance properties.     

Luteolytic prostaglandins. Synthesis and biological activity.

Analogues of PGF2 alpha with enhanced luteolytic activity were synthesized using the Corey synthesis. The luteolytic activity of the new prostaglandins was tested in the hamster. In addition the smooth muscle activity of the new compounds was compared with that of PGA2 on the longitudinal strip of rat stomach fundus. Structure-activity relationships in the new series of 17,18,19,20-tetranor-16-thienyl-oxy-PGF2 alpha are discussed.     

Synthesis of lower chain allenic prostaglandins (1)

The synthesis of four lower chain allenic prostaglandin F_α analogues IXA-D is described.The allenyl moiety has only occasionally been incorporated into the prostanoid skeleton and in all the examples thus far reported ·(2,3), this functionality is located in the upper side chain at carbons 4–6. This communication describes the synthesis of four isomeric allenyl PGF_α derivatives wherein the cumulated diene system is situated at positions 13–15.     

Synthesis of pregnenoic acid derivatives possessing structural elements of prostaglandins

Pregneoic acid derivative V in which the character of functional groups and distances between them (expressed in terms of C-C bonds) resemble those occurring in prostaglandins has been synthetised. 3beta-Hydroxyandrost-5-en-17-one acetate VII was converted to ethyl 3beta-acetoxypregn-5-en-21-oate XIIa via a Reformatsky reaction followed by dehydration of adduct VIIIa and selective hydrogenation of the diene X. Compound XIIa was then transformed into trienone XIII by oxidation of the 3beta-hydroxy-5-ene XIIc with DDQ. The trienone XIII was subsequently epoxidised with alkaline hydrogen peroxide and m-chloroperbenzoic acid to give diepoxide XV which was reduced with aluminum amalgam to the final product V.     

Synthesis of prostaglandins by subpopulations of human peripheral blood monocytes

The ability of monocytes/macrophages to regulate various aspects of immunologic responses may in part depend on their release of soluble substances such as prostaglandins. Using quantitative gas-liquid chromatography/mass spectrometry, prostaglandin E₂ was found to be the major prostaglandin synthesized in culture by human peripheral blood monocytes. Subjecting these cells to discontinuous density gradient fractionation demonstrated significant differences in the synthesis of prostaglandins E₂ and E₁ among the resulting monocyte subpopulations.     

Synthesis and nucleic acids binding properties of diastereomeric aminoethylprolyl peptide nucleic acids (aepPNA)

A general synthetic method for Fmoc-protected monomers of all four diastereomeric aminoethyl peptide nucleic acid (aepPNA) has been developed. The key reaction is the coupling of nucleobase-modified proline derivatives and Fmoc-protected aminoacetaldehyde by reductive alkylation. Oligomerization of the aepPNAs up to 10mer was achieved by Fmoc-solid phase peptide synthesis methodology. Preliminary binding studies of these aepPNA oligomers with nucleic acids suggested that the "cis-" homothymine aepPNA decamers with (2'R,4'R) and (2'S,4'S) configurations can bind, albeit with slow kinetics, to their complementary RNA [poly(adenylic acid)] but not to the complementary DNA [poly(deoxyadenylic acid)]. On the other hand, the trans homothymine aepPNA decamers with (2'R,4'S) and (2'S,4'R) configurations failed to form stable hybrid with poly(adenylic acid) and poly(deoxyadenylic acid). No hybrid formation could be observed between a mixed-base (2'R,4'R)-aepPNA decamer with DNA and RNA in both antiparallel and parallel orientations.     

Synthesis and antiproliferative activity of two diastereomeric lignan amides serving as dimeric caffeic acid-l-DOPA hybrids

Two new diastereomeric lignan amides (4 and 5) serving as dimeric caffeic acid-l-DOPA hybrids were synthesized. The synthesis involved the FeCl₃-mediated phenol oxidative coupling of methyl caffeate to afford trans-diester 1a as a mixture of enantiomers, protection of the catechol units, regioselective saponification, coupling with a suitably protected l-DOPA derivative, separation of the two diastereomers thus obtained by flash column chromatography and finally global chemoselective deprotection of the catechol units. The effect of hybrids 4 and 5 and related compounds on the proliferation of two breast cancer cell lines with different metastatic potential and estrogen receptor status (MDA-MB-231 and MCF-7) and of one epithelial lung cancer cell line, namely A-549, was evaluated for concentrations ranging from 1 to 256 μM and periods of treatment of 24, 48 and 72 h. Both hybrids showed interesting and almost equipotent antiproliferative activities (IC₅₀ 64–70 μM) for the MDA-MB-231 cell line after 24–48 h of treatment, but they were more selective and much more potent (IC₅₀ 4–16 μM) for the MCF-7 cells after 48 h of treatment. The highest activity for both hybrids and both breast cancer lines was observed after 72 h of treatment (IC₅₀ 1–2 μM), probably as the result of slow hydrolysis of their methyl ester functions.     

Synthesis of prostaglandins by the ductus arteriosus of the bovine fetus

Previous studies demonstrated that prostaglandins are local or tissue hormones which can be released from blood vessel walls. In the present study, we investigated the capacity of bovine ductus arteriosus to synthetize prostaglandins . After incubation of slices of ductus arteriousus in Krebs' solution with (1-¹⁴C) arachidonic acid for 3 hours, more than 40% of the radiolabeled material recovered from the incubating medium were metabolites of arachidonic acid. The major product was indistinguisable from 6 keto-PGF_1α as determined by its chromatographic mobility and resistance to alkaline conversion to PGB.The PGI₂ synthetic capacity of the ductus arteriosus, as revealed by the predominance of its major metabolite 6 keto-PGF_1α, suggests that this metabolic pathway of arachidonic acid may contribute to the hemodynamic changes occurring during fetal life and at birth.     

Synthesis of prostaglandins by the ductus arteriosus of the bovine fetus

Previous studies demonstrated that prostaglandins are local or tissue hormones which can be released from blood vessel walls. In the present study, we investigated the capacity of bovine ductus arteriosus to synthetize prostaglandins in vitro. After incubation of slices of ductus arteriosus in Krebs' solution with (1-14C) arachidonic acid for 3 hours, more than 40% of the radiolabeled material recovered from the incubating medium were metabolites of arachidonic acid. The major product was indistinguishable from 6 keto-PGF1alpha as determined by its chromatographic motility and resistance to alkaline conversion to PGB. The PGI2 synthetic capacity of the ductus arteriosus, as revealed by the predominance of its major metabolite 6 keto-PGF1alpha, suggests that this metabolic pathway of arachidonic acid may contribute to the hemodynamic changes occurring during fetal life and at birth.