9,12-Dibenzothiazolylhypericin and 10,11-Dibenzothiazolyl-10,11-didemethylhypericin: Photochemical Properties of Hypericin Derivatives Depending on the Substitution Site

Summary. Investigating the properties of similar but regioselectively differently substituted hypericin derivatives, 9,12-dibenzothiazolylhypericin was synthesized and compared with the recently prepared 10,11-analogue. A significant difference in the ability to generate singlet oxygen and/or reactive oxygen species and different absorption spectra of these two derivatives were observed.     

Syntheses and Properties of Two Heterocyclically Substituted Hypericin Derivatives: 10,11-Dibenzothiazolyl-10,11-didemethylhypericin and 10,11-Dibenzoxazolyl-10,11-didemethylhypericin

Summary. The syntheses of the two heterocyclically substituted title hypericin derivatives were achieved starting either from 6-benzothiazolyl-tri-O-methyl-6-demethylemodin or 6-benzoxazolyl-tri-O-methyl-6-demethylemodin. The use of microwave assisted synthesis for the preparation of these anthraquinone synthons and the chemical as well as photochemical properties of the corresponding unique hypericin derivatives, which might constitute new photodynamic therapy agents, are reported. The tautomeric and stereochemical aspects of these hypericin derivatives were investigated by means of semiempirical calculations (AM1).     

Syntheses and Properties of Two Heterocyclically Substituted Hypericin Derivatives: 10,11-Dibenzothiazolyl-10,11-didemethylhypericin and 10,11-Dibenzoxazolyl-10,11-didemethylhypericin

The syntheses of the two heterocyclically substituted title hypericin derivatives were achieved starting either from 6-benzothiazolyl-tri-O-methyl-6-demethylemodin or 6-benzoxazolyl-tri-O-methyl-6-demethylemodin. The use of microwave assisted synthesis for the preparation of these anthraquinone synthons and the chemical as well as photochemical properties of the corresponding unique hypericin derivatives, which might constitute new photodynamic therapy agents, are reported. The tautomeric and stereochemical aspects of these hypericin derivatives were investigated by means of semiempirical calculations (AM1).     

Synthesis of 10,11‐Didehydro Cinchona Alkaloids and Key Derivatives

A series of 10,11‐didehydro Cinchona alkaloids containing an ethynyl group at C(3) were prepared efficiently in two steps from the naturally occurring Cinchona alkaloids (Scheme 1). 10,11‐Didehydroquinine ( 4c ) and 10,11‐didehydroquinidine ( 4a ) belong to a significantly new class of semi‐natural Cinchona alkaloids. They are more polar and basic than the natural compounds and serve as versatile building blocks for further functionalization; they were transformed into the corresponding 11‐halo and 11‐pseudohalo derivatives and (Z)‐vinyl halides (Schemes 2 and 3). The conformation of the alkaloids was elucidated by NOE and X‐ray crystal diffraction analysis of 4a (Fig.), and the cytostatic activity of selected didehydroquinidine derivatives was evaluated (Table 5).     

Synthesis of fluorosubstituted 10,11-dihydrodibenz[b,f][1,4]oxazepines

The synthesis of a series of polyfluorinated derivatives of 10,11-dihydrodibenz[b,f][1,4]oxazepine and dibenz[b,f][1,4]oxazepine-11(10 H)-one has been effected.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1679–1682, December, 1990.     

Derivatives of 10,11-dihydro-5H-dibenzo[a,d] cycloheptene and related compounds. III. Azaketones

The preparation and properties of four isomeric azadibenzoeycloheptenones 3 and their 10,11-dihydro derivatives 2 are described. The ketones 2 were prepared by cyclization of appropriately substituted phenethylpyridine carboxylic acids and dehydrogenated to 3 . Four monochloro derivatives 24 of the 4-azaketone 2d are also described.     

Neurotrope und psychotrope Substanzen, 5. Mitt.: Synthese neuer Aminoderivate von 10,11-Dihydrodibenzo-[a,d]cyclohepten und 10,11-Dihydrodibenzo[b,f]thiepin

Zusammenfassung Im Rahmen der Suche nach neuen neurotropen und psychotropen Substanzen, besonders nach antidepressiv wirkenden Psychopharmaka, wurde eine systematische präparative Arbeit in den Gruppen der 10-substituierten Derivate des 10,11-Dihydrodibenzo[a,d]cycloheptens (I) und des 10,11-Dihydrodibenzo[b,f]-thiepins (II) unternommen. Im ersten Fall war die Ausgangssubstanz das Keton XIV, das mit üblichen Methoden zum basischen Äther XVI, zu Aminen und Derivaten XVIII–XXII und schließlich in dieMannich-Base XXVI übergeführt wurde. DieBeckmannsche Umlagerung des Oxims XVII eröffnete den Weg zu Derivaten eines neuen Systems, des 5,6,7,12-Tetrahydrodibenz[b,e]azocins (Verbindungen XXVIII, XXX und XXXI). Auch im zweiten Fall bildete das entsprechende Keton (XXXVIII) die Schlüsselsubstanz, die einerseits zu Aminen mit der Aminogruppe in der Seitenkette (XXXIX, XL, XLII, LV, LVI), anderseits zu Aminen mit der direkt am Skelett haftenden Aminogruppe (XLIV–LIII) umgesetzt wurde. Außer den angeführten Aminen wurde in allen drei Gruppen eine Reihe von neutralen Verbindungen hergestellt (Zwischenprodukte und Nebenprodukte), deren Struktur meistens mit Hilfe der Spektren geklärt wurde. Die vorläufigen Ergebnisse der pharmakologischen Prüfung einiger Produkte deuten interessante Wirksamkeit an, besonders vom Standpunkt der erwarteten neurotropen und psychotropen Eigenschaften aus.

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In the effort to find new neurotropic and psychotropic substances a systematic chemical study was undertaken in the groups of the 10-substituted derivatives of 10,11-dihydrodibenzo[a,d]-cycloheptene (I) and 10,11-dihydrodibenzo[b,f]thiepine (II). In the first case the ketone XIV was transformed by usual methods into the basic ether XVI, to the amines and derivatives XVIII–XXII, and to theMannich base XXVI. TheBeckmann rearrangement of the oxime XVII opened the way to derivatives of a new system — 5,6,7,12-tetrahydrodibenz[b,e]azocine (compounds XXVIII, XXX and XXXI). In the second case (derivatives of II) the syntheses started from the ketone XXXVIII and two series of amines were prepared: with the amino group in the side chain (XXXIX, XL, XLII, LV, LVI) and with the amino group attached directly to the skeleton (XLIV–LIII). In addition to the amines several neutral compounds in either group were synthesized (intermediates and byproducts), the structure of which was elucidated mainly by means of the spectra. Preliminary results of the pharmacological testing show a rather important degree of activity of some substances, especially in the line of the expected neurotropic and psychotropic properties.

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mit technischer Hilfe von

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Herrn Professor Dr.Hermann Bretschneider zum 60. Geburtstag gewidmet

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4. Mitt.:J. O. Jílek, K. Pelz, D. Pavlíková undM. Protiva, Coll. Czechoslov. Chem. Commun.30, im Druck (1965).     

Visible-Light-Mediated Dearomatisation of Indoles and Pyrroles to Pharmaceuticals and Pesticides

Dearomatisation of indole derivatives to the corresponding isatin derivatives has been achieved with the aid of visible light and oxygen. It should be noted that isatin derivatives are highly important for the synthesis of pharmaceuticals and bioactive compounds. Notably, this chemistry works excellently with N-protected and protection-free indoles. Additionally, this methodology can also be applied to dearomatise pyrrole derivatives to generate cyclic imides in a single step. Later this methodology was applied for the synthesis of four pharmaceuticals and a pesticide called dianthalexin B. Detailed mechanistic studies revealed the actual role of oxygen and photocatalyst.     

Synthesis of 2,2''''-(Substituted Arylmethylene)bis(1,6,6-trimethyl- 6,7,8,9-tetrahydrophenanthro[1,2-b]furan-10,11-dione) Derivatives

Tanshinones are a series of quinone diterpenes which are isolated from Salvia miltiorrhiza Bunge known as “Danshen” in Chinese traditional medicine. They have broad pharmacological activities, such as antibacterial, anti-tumor and anti-platelet aggregation1. Tanshinones’ derivatives have been used to treat the coronary disease, cerebrovascular diseases as well as neurasthenic insomnia in clinic2. Tanshinone IIA is one of the main components of tanshinones and characterized by the presenc…     

Metallations of 5 H-dibenz [b,f] azepine and 10,11-dihydro-5H-dibenz [b,f] azepine. Synthesis of 4-substituted derivatives

The synthesis of 4-substituted 5 H-dibenz [b, f] azepines and 10, 11-dihydro-5 H-dibenz [b, f] azepine resulting from the reaction of the corresponding 4, 5-dilithio derivatives and different N, N-dimethylamides is reported. The total assignment of the pmr spectra of the prepared formyl derivatives based on decoupling experiments is also described.     

Synthesis of substituted 10,11-dihydro-5H-dibenz[b,f]azepines; key synthons in syntheses of pharmaceutically active compounds

Substituted 10,11-dihydro-5H-dibenz[b,f]azepines are key synthons in the syntheses of a number of pharmaceutically active compounds such as imipramine, chlorimipramine, and desimipramine analogues. A facile synthesis of substituted 10,11-dihydro-5H-dibenz[b,f]azepines is described, starting out from com mercially available 2-bromotoluenes or 2-nitrotoluenes. Initial α-bromination with N-bromosuccinimide and subsequent reaction with triethylphosphite afforded the corresponding benzyl phosphonic ester deriva tives. After reaction with benzaldehyde derivatives, the expected Horner-Emmons reaction products were obtained. Hydrogenation gave the amino derivatives which were transformed into the corresponding formamides. Under Goldberg conditions [1], the final ring closing step was performed to give the substituted 10,11-dihydro-5H-dibenz[b,f]azepines in 46–75% yield.     

Photoinduced activation of molecular oxygen by various porphyrins,bis-porphyrins,phthalocyanines, pyridinoporphyrazins,and their metal derivatives

Aerobic irradiation of tetraphenylporphyrins, phthalocyanines, tetra-t-butylphthalocyanines, tetracarboxylphthalocyanines, tetrapyridinoporphyrazins and some of their metal derivatives with visible light (λ > 420 nm) give singlet oxygen by energy transfer and oxygen superoxide by electron transfer, but some of their Cu, Zn of Pt derivatives are efficient quenchers for superoxide formation.     

10,11-Methylene and 11-methyl-prostaglandins

The title compounds 6 and 7 have been prepared from a natural occurring PG-A₂ derivative. The structure and configuration of these novel prostaglandins are deduced from their mode of preparation and from their spectroscopic properties.     

The polar nature of 2,1,3-benzoxadiazole, -benzothiadiazole, -benzoselenadiazole and derivatives as determined by their electric dipole moments

Permanent electric dipole moments have been determined in benzene solutions at 25° for the oxygen, sulfur, and selenium series of 2,1,3-benzodiazoles. The derivatives studied contained 4, 5, and 6 substituted methyl, chloro, nitro, and amino groups. The dipole moment data of the derivatives were analyzed relative to that of the parent species which allowed deductions to be made about the mesomeric structures operating in the compounds. The mesomeric charge transfer increases regularly from the oxygen to the selenium structures, being nearly undetected in 2,1,3-benzoxadiazole derivatives and very pronounced in the 2,1,3-benzoselenadiazoles.     

Synthesis and Photochemistry of Novel 3,5-Diacetyl-1,4-dihydropyridines. II [1]

In continuation of previous work some novel 3,5-diacetyl-1,4-dihydropyridine derivatives were synthesized and their photochemical behavior was studied under oxygen and argon atmosphere. Oxidation of the dihydropyridine ring and formation of pyridine derivatives was the result of the reaction. The presence of oxygen affects not only on the rate of oxidation, but also the formation of some unidentified by-products was observed on irradiation under this atmosphere.     

An ESR Study on Singlet Oxygen Photoproduction of the Meso-Tetrakis-(Substituted Phenyl) Porphine Derivatives

The ability of meso-tetrakis- (substituted phenyl) porphine derivatives for photo-generating singlet oxygen (O2) is studied by ESR spectrometry. The results show that the singlet oxygen yields of most of porphine derivatives are higher than that of HPD. It is also exhibited that the nature and structure of the substituent at the meso position are closely related to the photo-sensitizing ability of meso-tetrakis-(substituted phenyl) porphine.     

Synthesis and Photochemistry of Novel 3,5-Diacetyl-1,4-dihydropyridines. II [1]

Summary. In continuation of previous work some novel 3,5-diacetyl-1,4-dihydropyridine derivatives were synthesized and their photochemical behavior was studied under oxygen and argon atmosphere. Oxidation of the dihydropyridine ring and formation of pyridine derivatives was the result of the reaction. The presence of oxygen affects not only on the rate of oxidation, but also the formation of some unidentified by-products was observed on irradiation under this atmosphere.     

SYNTHESIS,REACTIVITY AND CONFORMATION OF 10,11-DIHYDRODIBENZO-[b,f]PHOSPHEPIN AND DIBENZO[b,f]PHOSPHEPIN DERIVATIVES. PHOSPHORUS ANALOGUES OF IMINOBIBENZYL ANTIDEPRESSANTS

Abstract

Derivatives of the novel dibenzo[b,f]phosphepin system are prepared from 10,11-dihydro-5-phenyl-5H-bibenzo[b,f]phosphepin 5-oxide (2). New members in the 10,11-dihydro-5H-dibenzo[b,f]phosphepin series, including phosphorus analogues (7, 10) of the andidepressant drug imipramine (30), are also reported. Products of nucleophilic substitution at tetrahedral phosphorus in 2 appear to be determined by the relative apicophilicity of the nucleophile. Conformational analysis based on ¹H NMR data suggests folded (“butterfly”) conformation for the tricyclic compounds. The twisted boat conformation of the central ring in the 10,11-dihydro compounds bears a pseudo-equatorial P[dbnd]O oxygen or a P[dbnd]S sulfur, in solution. Symmetric AA‘BB’ spin systems are found in 4,5 and 7, and their solution conformations appear to be similar to those of analogous 10,11-dihydrodibenzo[b,f]azepine derivatives. The interaction of some compounds with NMR shift reagents and their mass spectral fragmentations are discussed.     

meso—四—（取代苯基）卟吩衍生物产生单线态氧的ESR研究

随着肿瘤光动力疗法(Photodynamic Therapy,PDT)的不断发展,出现了一系列新光敏剂,其中,meso-四-(取代苯基)卟吩衍生物是一类肿瘤选择性摄入率高、理化性质稳定的光动力敏化剂,近年来,作者设计并合成了一组meso-四-(取代苯基)卟吩衍生物,并初步观察了它们对细胞及小鼠移植瘤的光动力学效应,为了进一步比较不同卟吩衍生物的光敏化     

Highly regioselective synthesis of dicyano-8a,10,11-trihydropyrrolo[1,2-a][1,10]phenanthrolines via a domino-Knoevenagel-cyclization

1,10-Phenanthrolinium N-ylides,can react with malonitrile and aromatic aldehydes via a domino-Knoevenagel cyclization to afford a new class of trihydropyrrolo[1,2-a][l,10]phenanthroline derivatives as stable helical compounds in a simple,mild,and efficient protocol in excellent yields.