ACTION OF WITTIG‐HORNER REAGENTS ON o-QUINONES

Abstract

When 3,4,5,6-tetrachloro-1,2-benzoquinone (1) was reacted with two molar amounts of triethylphosphonoacetate (I), the corresponding 5,6,7,8-tetrachlorocoumarin-4-carbethoxy-3-diethylphosphonate (4) was obtained. Moreover, phenanthrene-9,10-quinone (2) was converted by reaction of Wittig-Horner reagent (I) into 2,3-dicarbethoxy-phenanthro[9,10-b]dihydrofuran (5) and the dimeric form (6). On the other hand, adducts (7) and (8) were isolated from the reaction of acenaphthenequinone (3) with triethylphosphonoacetate (I). Possible reaction mechanisms are considered and the structure of the new compounds (4), (5, 6) and (7, 8) was confirmed on the basis of the elemental analysis and spectral studies.     

(±)-Shegansu B,Gnetuhainin F, (±)-Maackin A与(±)-Cassigarol E的全合成

对四种天然二聚二苯乙烯类化合物Shegansu B (1), Gnetuhainin F (1a), Maackin A (2)以及Cassigarol E (3)的全合成进行了研究. 以3,5-二羟基苯甲酸(4)为起始原料, 经六步反应制得异丹叶大黄素(13)和白皮杉醇(14), 在HRP/H₂O₂酶催化氧化体系中, 13和14分别进行自身的氧化偶联得到各自的二聚产物. 首次完成了1a, (±)-2和(±)-3的全合成, 并以较文献报道为高的氧化偶联产率合成了(±)-1.     

SYNTHESIS OF NEW ANTHRACYCLINE DERIVATIVES CONTAINING PYRUVIC,ASPARTIC, OR N-ACETYLASPARTIC ACID MOLECULE

ABSTRACT

The new anthracycline analogues (2–10) as potential anticancer agents were synthesized from daunomycin (1a) and doxorubicin (1b). Compounds 2, 6, and 7 were prepared by the nucleophilic displacement type esterification of a 14-bromodaunomycin (1c) with a sodium pyruvate, aspartate, and N-acetylaspartic acid, respectively. Whereas compounds (3, 8) and (4, 9) were prepared by the reaction of daunomycin (1a) or doxorubicin (1b) with one equivalent of the corresponding acids in the presence of EDCI/PP, compounds (5, 10) were obtained from 1b by reaction with two equivalents of the corresponding acids in the same manner.     

Zur Synthese der 4-Dialkylamino-5,6-dihydro-2(1H)-pyridinthione sowie entsprechender 4-Alkylamino- bzw. 4-Arylaminoverbindungen

The rearrangement of 1-alkyl- and 1-aryldihydro-6-methyl-2(1H)-pyrimidinethiones (1 a) or-ones (1 b) and of methylene compounds (2a, 2b) resp., to 4-alkylamino- and 4-arylaminodihydro-2(1H)-pyridinethiones (4 a) or-ones (4 b) takes place via the corresponding 3-alkylamino- and 3-aryl-amino-3-butenylisothiocyanates (3 a) or-isocyanates (3 b). Dialkylamino-dihydro-2(1H)-pyridinethiones (10) are formed by heating dihydro-6-methyl-2(1H)-pyrimidinethiones (6 a) and 3,4-dihydro-6-methyl-1,3-thiazin-2-thiones (6 b) with dialkylformamides and by the reaction of secondary amines with tetrahydro-6-hydroxy-6-methyl-1,3-thiazin-2-thiones (5 a), with N,N-dialkyl-N-(3-oxobutyl)-thioureas (7) and 3-oxobutyl isothiocyanates (8). A general method for the preparation of10 is the reaction of dialkylammoniumrhodanides12, N,N-dialkylthioureas13 and dialkylammonium chlorides and KCNS, resp., with 3-alken-2-ones14 and 4-hydroxy-2-alkanones15, resp. Methyl ketones such as acetone, which readily undergo the aldol condensation, behave analogously. The reactions described take place via the intermediate aminoalkenyl isothiocyanates (9).     

SYNTHESE DE SPIROPHOSPHORANES CONTENANT UNE LIAISON P–C

Abstract

Les réactions des oxa et oxazaspirophosphoranes à liaison P–H (1)–(4) avec les doubles liaisons activées C?C conduisent aux spirophosphoranes à liaison P_VC (9)-(20). Nous considérons les composés (9)-(20) comme des précurseurs de phosphonates. Le mécanisme de ces réactions a été examiné.

The reaction of oxa and oxazaspirophosphoranes containing P–H bond (1)-(4) with C?C activated double bond lead to spirophosphoranes containing P_V-C bond (9)-(20). We consider compounds (9)-(20) as phosphonates precursors. The mechanism of these reactions has been examined.     

Oxazepines and thiazepines,XXIV synthesis of optically active 2,3-dihydro-2-methyl-1,5-benzoxazepin-4(5H)-ones

Summary 2,3-Dihydro-2(R)-methyl-1,5-benzoxazepin-4(5H)-one [(R)-3] and its enantiomer (S)-3 have been synthesized via the optical resolution and subsequent chemical transformations of (±)-3-(2-nitrophenoxy)butyric acid (1). Compounds (R)-3 and (S)-3 were converted into optically active 1,5-benzoxazepines (R)-7–(R)-14 and (S)-15–(S)-32.

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Oxazepine und Thiazepine, XXIV: Darstellung optisch aktiver 2,3-Dihydro-2-methyl-1,5-benzoxazepin-4(5H)-one

Zusammenfassung 2,3-Dihydro-2(R)-methyl-1,5-benzoxazepin-4(5H)-on [(R)-3] und sein Enantiomeres (S)-3 wurden durch Racemattrennung und weitere chemische Umsetzungen von (±)-3-(2-Nitrophenoxy)buttersäure (1) dargestellt. Die Verbindungen (R)-3 und (S)-3 wurden in die optisch aktiven 1,5-Benzoxazepine (R-7 bis (R)-14 und (S)-15 bis (S)-32 übergeführt.

     

Microbial carbonylation and hydroxylation of 20(R)-panaxadiol by Aspergillus niger

20(R)-panaxadiol (PD) was metabolised by the fungus Aspergillus niger AS 3.3926 to its C-3 carbonylated metabolite and five other hydroxylated metabolites (1–6). Their structures were elucidated as 3-oxo-20(R)-panaxadiol (1), 3-oxo-7β-hydroxyl- 20(R)-panaxadiol (2), 3-oxo-7β,23α-dihydroxyl-20(R)-panaxadiol (3), 3,12-dioxo- 7β,23β-dihydroxyl-20(R)-panaxadiol (4), 3-oxo-1α,7β-dihydroxyl-20(R)-panaxadiol (5) and 3-oxo-7β,15β-dihydroxyl-20(R)-panaxadiol (6) by spectroscopic analysis. Among them, compounds 2–6 were new compounds. Pharmacological studies revealed that compound 6 exhibited significant anti-hepatic fibrosis activity.     

Über das 4-Hydroxy-6,6-dimethyl-5,6-dihydro-2(1H)-pyridinthion bzw.-on und die entsprechenden Tautomeren

The tautomers, 4-hydroxy-5,6-dihydro-6,6-dimethyl-2(1H)-pyridinethione (1) and 6,6-dimethyl-2-thioxo-4-piperidone (2) resp., and 4-hydroxy-5,6-dihydro-6,6-dimethyl-2(1H)-pyridone (9) and 6,6-dimethyl-2,4-piperidinedione (10) resp. were synthesized by hydrolysis of 4-amino-5,6-dihydro-6,6-dimethyl-2(1H)-pyridinethiones (4, 5) and-ones (11, 12).1, 2 and9, 10 undergo an aminolysis in amines to the corresponding 4-aminodihydro-2(1H)-pyridinethiones4, 5 and-ones11, 12 resp.

     

Natural product chemistry,part 137: Oxidation of acridone alkaloids: Synthesis of 5-methoxyacronycine

Summary Epoxidation of the acridone alkaloid acronycine (1) resulted in hydroxylation at the aromatic ring giving 5-hydroxyacronycine (3). The same reaction on 1,3-dimethoxy-10-methyl-9(10H)-acridinone (5) gave 1,3-dimethoxy-2-hydroxy-10-methyl-9(10H)-acridinone (6), 1,3-dimethoxy-2-hydroxy-4-peroxy-10-methyl-9(10H)-acridinone (8), and 1,3-dimethoxy-2,4-diperoxy-10-methyl-9(10H)-acridinone (9).

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Naturstoffchemie, 137. Mitt.: Oxidierung von Acridonalkaloiden: Synthese des 5-Methoxyacronycins (Kurze Mitt.)

Zusammenfassung Die Epoxidierung des Acridonalkaloids Acronycin führte zu einer Hydroxylierung des aromatischen Rings, wobei 5-Hydroxyacronycin (3) entstand. Die gleiche Reaktion mit 1,3-Dimethoxy-10-methyl-9(10H)acridinon (5) ergab 1,3-Dimethoxy-2-hydroxy-10-methyl-9(10H)acridinon (6), 1,3-Dimethoxy-2-hydroxy-4-peroxy-10-methyl-9(10H)acridinon (8) und 1,3-Dimethoxy-2,4-diperoxy-10-methyl-9(10H)acridinon (9).

     

Reaction of β‐Lapachone with 1,2‐Diamines: Facile Synthesis of Novel Tetracyclic Pyrazines

The reactions of β‐lapachone (1) with 1,2‐diaminoethane (2) and 1,2‐diaminopropane (4) gave the tetracyclic pyrazine derivatives (3) and mixtures of (5) and (6), respectively, while reaction with o‐phenylene diamine (7) gave the quinoxaline derivative (8). The structure of pyrazine derivative (3) is confirmed by single‐crystal X‐ray diffraction study.     

Preparation of (R)-(+)-lithium lactate

Summary Optically pure (R)-(+)-lithium lactate (7) and its benzyl ether analogue (6a) were obtained from acetaldehyde usingEliel's 1,3-trans-oxathiane (1) as the chiral auxiliary for chromatographic separation.

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Herstellung von (R)-(+)-Lithiumlactat

Zusammenfassung Optisch reines (R)-(+)-Lithiumlactat (7) und sein Benzyletheranaloges (6a) wurden mittelsEliels 1,3-trans-Oxathian (1) als chiralem Hilfsstoff zur chromatographischen Trennung aus Acetaldehyd hergestellt.

     

UV-stability and UV-protective activity of alkaloids from the marine sponge Zyzzya fuliginosa

Alkaloids from the marine sponge Zyzzya fuliginosa damirones A (1) and B (2); makaluvamines H (3), C (4), G (5), and L (6); and zyzzyanones A (8) and B (9) were investigated for the ability to protect egg-cell membranes of the sea urchin Strongylocentrotus nudus from UV-radiation. Damirones, zyzzyanones, and tricyclic makaluvamines C (4) and H (3) exhibited the greatest membrane-protective activity. It was shown that makaluvamines G (5) and L (6) were converted by UV-irradiation into damirones A (1), B (2), tricyclic makaluvamines H (3), C (4), and zyzzyanones A (8) and B (9), respectively. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 62–64, January–February, 2006.     

ORGANISCHE PHOTOCHEMIE XXIX1,2 Synthese und Photoreaktionen eines Aroyl-Diphenylphosphins‐Eine neuartige Photoinduzierte Sauerstoff-Transferreaktion

Abstract

Es wird die Synthese und Photolyse des neuen [2-Brom-α-oxo-phenylmethan]-diphenylphosphins (5) beschrieben. UV-Bestrahlung von (5) in Benzol liefert Produkte durch x-Spaltungen (6 und 7) und Photosubstitutionen (7 und 8) sowie das Phosphinoxid (9) durch neuartige Umlagerungsreaktion. Die Bildung von (9) wird durch photoinduzierten 1,2-Sauerstofftransfer aus der Carbonylgruppe auf den Phosphor erklärt. Von (9) wird eine Röntgenstrukturanalyse vorgelegt.

Synthesis and photolysis of the new [2-bromo-α-oxo-phenylmethane]-diphenylphosphine (5) is described. U. v. irradiation of (5) in benzene yields products via α-cleavages (6 and 7), and photosubstitutions (7 and 8), and the phosphine oxide (9) in a novel rearrangement reaction. The formation of (9) is interpreted by photoinduced 1,2-transfer of oxygen from the carbonyl function onto the phosphorous atom. An X-ray structure analysis of (9) is presented.     

Synthesis of 3-aminothiophene-2-thioamides

Summary 4-Dimethylamino-5,6-dihydro-2H-thiopyran-2-thiones (1) were alkylated to N,N-dimethyl-6-methylthio-2H-thiopyran-4(3H)-iminiumiodides (2). Aminolysis of the latter with ammonia led to 6-dimethylamino-2H-thiopyran-4(3H)-iminiumiodides (3) which were hydrolyzed to 3-amino-N,N-dimethyl-2,4-pentadienthioamides (4). Ring closure with sulfur gave 3-aminothiophene-2-thioamides (5). The configurations of the pentadienthioamides (4) have been investigated by NOE experiments. The structures of the thiophene-2-thioamides (5) were established by means of two-dimensional NMR techniques.

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Synthese von 3-Aminothiophen-2-thiocarboxamiden

Zusammenfassung 4-Dimethylamino-5,6-dihydro-2H-thiopyran-2-thione (1) wurden zu N,N-Dimethyl-6-methylthio-2H-thiopyran-4(3H)-iminiumiodiden(2) alkyliert. Die Umsetzung mit Ammoniak führte zur Bildung von 6-Dimethylamino-2H-thiopyran-4(3H)-iminiumiodiden (3). Diese wurden zu 3-Amino-N,N-dimethyl-2,4-pentadienthioamiden (4) hydrolysiert. Beim Erhitzen mit Schwefel erfolgte Cyclisierung zu 3-Aminothiophen-2-thiocarboxamiden (5). Die Konfiguration der Pentadienthioamide (4) wurde mit NOE-Messungen untersucht, die der Thiophen-2-thiocarboxamide (5) mit Hilfe zweidimensionaler NMR-Methoden aufgeklärt.

     

Synthesis and antimicrobial activity of some 2-alkyl-2H-1,4-benzothiazin-3(4H)-ones and 2-alkylbenzo[d]imidazolo[2,1-b]-thiazolidin-3-ones

Summary Sodium 2-aminothiophenoxide (1) reacts with ethyl 2-bromoalkanoates (2) under direct cyclization to form 2-alkyl-2H-1,4-benzothiazin-3(4H)-ones (3). Reaction of the sodium salt of 2-mercaptobenzimidazole (4) with2 or 2-bromoalkanoic acids (5) affords only S-alkylated products (6 or7, respectively). The cyclization products — 2-alkylbenzo[d]imidazolo[2,1-b]thiazolidin-3-ones (8) — can be obtained only from the corresponding 2-(2-benzimidazolylthio)alkanoic acids (7) by the action of acetic anhydride. Both compounds3 and8 exhibit only moderate antimicrobial activity against some gram-positive bacteria.

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Synthese und antimikrobielle Wirkung von einigen 2-Alkyl-2H-1,4-benzothiazin-3(4H)-onen und 2-Alkylbenzo[d]imidazolo[2,1-b]thiazolidin-3-onen

Zusammenfassung Bei der Reaktion von Natrium-2-aminothiophenolat mit 2-Bromoalkansäure-ethylestern (2) entstehen als Cyclisierungsprodukte 2-Alkyl-2H-1,4-benzothiazin-3(4H)-one (3). Die Umsetzung von Natriumbenzimidazol-2-thiolat mit2 oder mit 2-Bromoalkansäuren (5) liefert nur S-Alkylierungsprodukte (6 oder7). Die Cyclisierungsprodukte — 2-Alkylbenzo[d]imidazolo[2,1-b]thiazolidin-3-one (8) — sind nur durch Umsetzung von entsprechenden 2-(2-Benzimidazolylthio)-alkansäuren (7) mit Acetanhydrid erhältlich. Die Verbindungen3 und8 weisen nur mäßige antimikrobielle Wirkung gegen einige gram-positive Bakterien aus.

     

EFFICIENT RESOLUTION OF (±)-1-(9-ANTHRYL)ETHYLAMINE

ABSTRACT

Conditions for efficient resolution of (±)-1-(9-anthryl)ethylamine ((±)-1) by fractional crystallization of its salts with (S)-(+)-mandelic acid (2) are reported. When crystallization was performed by fast addition of chloroform solution of an equivalent of (±)-1 to the hot chloroform solution of (+)-2, crystals of mandelate of (+)-1-(9-anthryl)ethylamine ((R,S)-3) are collected in 56% yield. (R)-(+)-1 (98.6% e.e.) is isolated by extraction from bicarbonate solution of mandelate salt. Ulterior collection of four crops afforded (R,S)-3 with 71.5% cumulative yield and >98% e.e. of (+)-1 in a any single crop. With only 0.5 equivalents of (+)-2 crystallization afforded (R,S)-3 in 47.4% yield and (+)-1 with 98.1% e.e.     

OPTICAL ISOMERS OF 2,2′-DIAMINOBIPHENYLBIS(ETHYLENEDIAMINE) COBALT(III) CHLORIDE AND ITS RELATED COMPLEXES1

Abstract

Several cobalt(III) complexes incorporating 2,2′-diaminobiphenyl(dabp) and other 2(2N)- or 4N-type ligands were prepared and resolved by chemical and chromatographic methods: (1) [Co(en)₂(dabp)]Cl₂2H₂O, (2) [Co(l-pn)₂(dabp)] (ClO₄)₃4H₂O, (3) [Co(l-chxn)₂(dabp)](ClO₄)₃3H₂O, (4) α-[Co(trien)(dabp)](ClO₄)₃, (5) α-[Co(2S,9S-dimetrien)(dabp)] (ClO₄)₃ 2H₂O, (6) α-[Co(3S,8S-dimetrien)(dabp)] (ClO₄)₃3H₂O, (7 [Co(tren)(dabp)]Cl₃5H₂O, (8) [Co(bpy)₂(dabp)] Cl₃3H₂O. The complexes (1), (4) and (8) gave one pair of enantiomers, Δ(Λ) and Λ(δ), and the complexes (2) and (3) gave only one Δ-isomer. The absolute configuration of the complexes (5) and (6) was found to be Λ, and that of (7) was not determined because of unsuccessful resolution. The three geometric isomers of the complex (2) were separated and their structures assigned.     

Eine neue Synthese von Nornarcein

N-benzylnornarceine-ethyl ester hydrochloride (3a) and N-benzylnornarceinehydrochloride (4a), both obtained byHofmann degradation of N-benzylnarcotinium bromide (2), are debenzylated catalytically to nornarceine-ethylester-HCl-salt (5) and nornarceine (6).Die HCl-Salze von N-Benzylnornarcein-äthylester (3a) und N-Benzylnornarcein (4a), erhältlich durchHofmann-Abbau aus N-Benzylnarcotiniumbromid (2), werden katalytisch zu Nornarcein-äthylester-Hydrochlorid (5) und Nornarcein (6) entbenzyliert.     

Synthesis of Novel Cyclodextrin Trimers

CD trimers (3 and 6) and CD dimers (4 and 7) have been synthesized by reaction of 6-deoxy-6-hydroxyethylamino-β-CD (1) with corresponding 1,3,5-tri(bromomethyl) benzene (2) or 1,3,5-tri (bromomethyl)-2,4,6-trimethylbenzene (5) in the presence of base.     

Synthesen von Heterocyclen, 99. Mitt.: Chinolizine und Indolizine IV: Eine Synthese von Hydroxy-benzochinolizinonen

Zusammenfassung An der Methylgruppe substituierte Chinaldine (1) reagieren mit monosubstit. Malonsäure-bis-2,4,6-trichlorphenylestern (2a-c) bei 250° zu Derivaten des Hydroxy-benzo[c]chinolizinons (4bzw.5). Aus Chinaldin selbst entstehen unter diesen Bedingungen Pyrono-chinolizinone (3). Analog erhält man bei der Umsetzung von 1-Methylisochinolin (9) mit2 2-Hydroxy-benzo[a]chinolizin-4-one (11) und aus 6-Alkylphenanthridinen (13) Dibenzoderivate des Chinolizinons (14). 2-Chinolylessigsäureester (6) addiert sogar Kohlensuboxid (C₃O₂) unter Bildung von 4-Äthoxy-carbonyl-3-hydroxy-benzo[c]chinolizin-1-on (8 a).

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2-Alkylquinolines (1) react with monosubstituted 2.4.6-trichlorophenyl malonates (2) at 250° to derivatives of hydroxy-benzo[c]quinolizinone (4 or5). The reaction of quinaldine itself with2 leads to pyrono-quinolizinones (3). The reaction of2 with 1-methylisoquinoline (9) yields 2-hydroxy-4H-benzo[a]quinolizin-4-ones11, and with 6-alkyl-phenanthridines (13) dibenzo[a, c]quinolizinones (14) are obtained. Carbon suboxide (C₃O₂) is added readily to ethyl 2-quinolyl acetate (6) yielding 4-ethoxy-carbonyl-3-hydroxy-1H-benzo[c]quinolizin-1-one (8 a).