Ab Initio Study of Prednisolone, 6α-Fluoroprednisolone, 9α-Fluoroprednisolone,and 6α,9α-Difluoroprednisolone

A theoretical study of prednisolone, 6-fluoroprednisolone, 9-fluoroprednisolone, and 6,9-difluoroprednisolone has been performed at the ab initio HF/6-31G, MP2/6-31G, and B3LYP/6-31G levels. Structural information and the electronic features of prednisolone and its derivatives and the synergistic effect of 6,9-difluoroprednisolone was examined. Contrary to the AM1 and MNDO results, we found 9-fluoroprednisolone is more stable than the 6-fluoroprednisolone. The increased corticosteroid activity of the 6,9-difluoroprednisolone is most likely due to electronic effects, mainly related to the receptor binding.     

Automatic assembly of skeleton structures. 3. Stereoselective synthesis,stereochemistry, and cyclization ofd,l-α,α'-dioxy-α,α'-di-tert-butylglutaric acid

Stereoselective synthesis of d,l-,-dioxy-,-di-tert-butylglutaric acid hydroxyiminolactonitrile (3) was conducted by the reaction of dipivaloylmethane with HCN in ether. The corresponding hydroxylacetonitrile (4) and amide (5), acid (6), and its ester (7), from which dilactone (8) was synthesized with preparative yields, were obtained from3. Benzyl amide (9) was obtained by the reaction of8 with BnNH₂. The iminolactone structure3 of dipivaloylmethane bis-cyanohyrin, thecis-pseudo-a orientation of the functional substituents in3–7 and9, and the structure of the dilactone8 were confirmed by the¹H,¹³C NMR,IR and mass spectra.For previous communication, see [2].N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 117977 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 7, pp. 1591–1601, July, 1992.     

α,α-Dicyanoethyl Acetate. A Reagent for Selective N-Acetylation

N-Aoetylation is one of the classical methods for protection of primary and secondary amino groups.¹ While there is a lavish repertoire of reagents and conditions available for its execution, few exhibit the desirable feature of discriminative action between hydroxyl and anino functions. This communication disseminates the use of α,α-dicyanoethyl acetate (1) as a selective N-acetylation agent.     

Stereoselective synthesis of uncommon α,α′-dialkyl-α-aminoacids. Part 1

The alkylation of the diastereomeric mixture of chiral morpholinone derivatives 4 and 5 occurs with good yield and trans induction. Cleavage of the alkylated products 6a,b,c,e gives enantiomerically pure uncommon (and sterically constrained) α,α′-dialkyl-α-aminoacids. The absolute configuration of the new stereocentres of 4, 5, 6 and 7 has been assigned on the basis of the ¹H-NMR spectra and NOE measurements.     

Mono-Protected Diamines. N-tert-Butoxycarbonyl-α,ω-Alkanediamines from α,ω-Alkanediamines

We wish to report a convenient pathway to N-tert-butoxycarbonyl-α,ω-alkanediamines 2a-e [H₂N(CH₂)χNHBOC; χ=2, 3, 4, 5 and 6; (75–90% yields)] by treatment of the corresponding α,ω-alkanediamine with di-tert-butyl dicarbonate in dioxane as the solvent. Only small amounts of the bis-substituted N.N′-tert-butoxycarbonyl-α,ω-alkanediamines 3a-e were formed (2–9%) which were easily removed by an aqueous workup. The α,ω-alkane-aza-diamine 4 was also mono-protected (62% yield of 5) by the same methodology.     

An enantiomerically pure bilirubin. Absolute configuration of (αR,α′R)-dimethylmesobilirubin-XIIIα

Enantiomerically pure (+)-(αR,α′R)-dimethylmesobilirubin-XIIIα 1 and its (αS,α′S) enantiomer ent-1 were synthesized in ten steps from simple precursors. Resolution was achieved at an early stage in the synthesis, with a racemic monopyrrole precursor rac-6 being converted to its amides 8 with (1S)-camphor-2,10-sultam. Resolution of 8 to 99% d.e. was accomplished in three crystallizations, and the absolute configuration of the acid 6 was deduced by X-ray crystallography of the more crystalline, diastereomerically pure amide 7. Circular dichroism spectroscopy of 1 showed intense bisignate Cotton effects: Δε^max₄₃₅=+344, Δε^max₃₉₁=−193 (CHCl₃), as expected for a molecular exciton, and consistent with a P-helical intramolecularly hydrogen-bonded ridge-tile conformation. The Cotton effect magnitudes of 1 match almost exactly those found for (−)-(βS,β′S)-dimethylmesobilirubin-XIIIα 11 and (+)-(αR,β′R)-dimethylmesobilirubin-XIIIα. However, the Cotton effect of the pseudo-meso diastereomer (αR,β′S)-dimethylmesobilirubin-XIIIα 12 is not zero. Its large positive exciton couplet and ¹H NMR NOE analysis confirm that an α-CH₃ exerts a greater steric demand than a β-CH₃—by a factor of ∼3.     

Untersuchungen über Phenthiazinderivate, 18. Mitt. Neue Derivate desα-Oxo-4, 10-trimethylen-phenthiazins

Zusammenfassung Aus der durch Einwirkung von Salzsäure auf Phenthiazin-9-oxyd-10-propionsäure gebildeten 2-Chlor-phenthiazin-10-propionsäure entsteht durch Ringschluß ein Gemisch zweier Chlor--oxo-4,10-trimethylen-phenthiazine. Bei der Umsetzung von -Oxo-4,10-trimethylen-phenthiazin-9-oxyd mit Salzsäure entstand nicht, wie erwartet, ein Chlorderivat, sondern ein dehydriertes -Oxo-4,10-trimethylen-phenthiazin, dessen Konstitution bewiesen wurde.     

Aminosäuren, 9. Mitt.: Farbreaktionen mit cyclischen Di- und Triacetylverbindungen

Zusammenfassung In früheren Arbeiten^{1, 3} haben wir über das Verhalten von o-Diacetylbenzol (I) und einer größeren Anzahl cyclischer Verbindungen mit zwei oder drei analogen Carbonylfunktionen gegenüber Aminosäuren berichtet, wobei außer I und Homologen das vicinale Triacetylbenzol (II) und ein Diacetylcyclohexen-Isomers (trans-IV)¹ Farbstoffbildung zeigten. Diese und einige weitere, auscis- undtrans-Diacetyläthylen und entsprechenden Dienen synthetisierten cyclischen o-Diacetylverbindungen (Tab. 1) werden im folgenden in ihrem Verhalten gegenüber den 6 Aminosäuren Gly, Lys, His, Met, Asp, Cys quantitativ geprüft.Mit 1 AbbildungFortsetzung der 4. Mitt., Mh. Chem.90, 924 (1959); 8. Mitt.: Mh. Chem.93, 841 (1962).Gleichzeitig 21. Mitt. der Reihe Acylderivate cyclischer Verbindungen; 20. Mitt.: Mh. Chem.93, 616 (1962).     

Untersuchungen über Phenthiazinderivate. 9. Mitteilung

Zusammenfassung -(10-Phenthiazinyl)-propionsäure und das daraus gebildete 4,10-(-Oxo-trimethylen)-phenthiazin sind wichtige Ausgangsprodukte für weitere Synthesen. Es wurden daher einige Derivate der ersteren Verbindung für die pharmakologische Untersuchung bereitgestellt und eine rationelle Darstellungsmethode der letzteren ausgearbeitet. Endlich wurden Nomenklaturvorschläge für das Keton diskutiert.     

Nitroderivate vonβ,β,β-Trihalo-α,α-bis-(4-alkoxybzw. 4-oxy-phenyl)-äthanen

Zusammenfassung Auf Grund von Modellbetrachtungen wurde die Existenz der in der Literatur beschriebenenOctanitro-Derivate von ,,-Trihalo-,-bis-(4-alkoxy-phenyl)-äthanen in Zweifel gezogen. Entsprechende Untersuchungen ergaben, daß es sich bei ihnen umTetranitro-Verbindungen handelt und daß es nicht möglich ist, diese DDT-Analogen mehr als vierfach zu nitrieren. Die Konstitution der Tetranitro-Verbindungen wurde durch Abbau bewiesen: Beim ,,-Trichlor-,-bis-(3,5-dinitro-4-methoxy-phenyl)-äthan (II) durch Überführung in das entsprechende Keton (VII), beim ,,-Trichlor-,-bis-(3,5-dinitro-4-äthoxy-phenyl)-äthan (IV) durch Entalkylierung und Methylierung zu II. Der Beweis der 3,3, 5,5-Stellung der Nitrogruppen in II und IV ist auch für andere Tetranitro-Derivate von ,,-Trihalo-,-bis-(4-X-phenyl)-äthanen (X=Substituenten I. Ordnung) von Bedeutung.Mitt. II der Reihe: Stereochemische Untersuchungen in der Diphenylmethanreihe.     

Comment on "Autoionization at the surface of neat water: is the top layer pH neutral, basic, or acidic?" by R. Vácha, V. Buch, A. Milet, J. P. Devlin and P. Jungwirth, Phys. Chem. Chem. Phys., 2007, 9, 4736

The surface of near-neutral water is basic due to the adsorption of hydroxide ions, not acidic as has been recently claimed.     

New variants in the total synthesis of 14β-hydroxy-17α,R-8α,9β-estradiol derivatives

Two procedures were developed for the synthesis of 17-alkyl-8,9-estra-1,3,5(10)-triene-3,14,17-triols from 3-methoxy-estra-1,3,5(10),8(9),14(15)-pentaene-17-one (1) using photosensitized oxidation by atmospheric oxygen or ionic hydrogenation in the presence of oxygen. It was shown that 17-hexynyl-8,9-estra-1,3,5(10)-triene-3,14,17-triol (23) and its 3-methoxy derivative (26) inhibit K⁺,Na⁺-ATPase, with inhibition degree increasing on introduction of an oxygen-containing substituent into position 17. For the first time steroids were found with ₂-adrenoblocking action.Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 1, pp. 207–212, January, 1993.