含2-三氟甲基苯并咪唑的双噁二唑硫醚及其亚砜衍生物的合成

芳甲酰肼和氯乙酸在二甲苯中反应生成了一系列的2-芳基-5-氯甲基-1,3,4-噁二唑(1a～1j), 继而与2-(2-三氟甲基苯并咪唑-1-亚甲基)-5-巯基-1,3,4-噁二唑(2)在乙醇-水的溶液中反应得到了一系列的含2-三氟甲基苯并咪唑的双噁二唑硫醚3a～3j, 再用硝酸氧化得到相应的亚砜衍生物4a～4j. 化合物的结构经元素分析, IR, ¹H NMR确证.     

含噁二唑肟醚取代的均三唑水杨醛席夫碱的合成及抗菌活性

4-氨基-5-(4-甲氧苯基)-3-巯基-均三唑(2)在无水乙酸钠作用下与β-氯苯丙酮(3)缩合得氨基三唑硫代苯丙酮(4). 化合物4与盐酸羟胺肟化得羰基肟化物5, 接着与水杨醛缩合得到席夫碱肟6, 用氯甲基噁二唑7a～7e对化合物6的肟羟基醚化得到目标物均三唑噁二唑肟醚1a～1e. 所合成的新化合物结构由元素分析和光谱数据表征, 体外抗菌活性也被试验.     

新型手性N,N′-双支套索冠醚的合成及其应用

(S)-苯丙氨醇和原氯乙酸三乙酯作用得到的手性酰胺醇和手性噁唑啉分别与1,7-二氮-12-冠-4反应, 得到了两种手性N,N′-双支套索冠醚N,N′-二[(S)-N-(1-羟甲基-2-苯基乙基)乙酰胺-2]-1,7-二氮-12-冠-4 (1a)和N,N′-二[(S)-4-苄基-噁唑啉-2-亚甲基]-1,7-二氮-12-冠-4 (1b). 前者应用于D/L-肉碱的手性分离; 后者的铜配合物用于重氮醋酸酯对烯烃的不对称环丙烷化反应.     

D-Glucosyl Kojic Acid Derivatives,Potential Precursors for the Cyclic Carboxylate Equivalents of Gaba Mimetic Agents

Abstract

Precursors for the cyclic carboxyl equivalents of γ-aminobutyric acid (GABA) were synthesized. 5-O-(2, 3, 4, 6-Tetra-O-acetyl-β-D-gluco-pyranosyl-2-[4-phenyl-1, 2, 3-triazol-1-yl)methyl]-4H-pyran-4-one could be prepared by the glucosidation of 2-chloromethyl-5-hydroxy-4H-pyran-4-one. Nucleophilic displacement of the chlorine with azide ion gave the corresponding azidodeoxy derivative that upon 1, 3-dipolar cycloaddition with phenylacetylene yielded the triazolyl derivative.     

An asymmetric isoxazole annulation

An Asymmetric isoxazole annulation proceeds from the (S)-O-methoxyphenylalaninol imine of (RS)-2-phen-ylpropionaldehyde (3). Deprotonation, quenching with 4-chloromethyl-3,5-dimethylisoxazole, and hydrolysis produced isoxazolylaldehyde (5), whose structure was confirmed by single crystal X-ray diffractometry. The absolute configuration of (-)-5 was established as (R)-by chemical correlation to the known (S)-(-)-4-methyl-4-phenyl-cyclohex-2-ene-1-one (7).     

Synthesis and Crystal and Molecular Structures of 2-Diethylaminomethyl- and 2-Chloromethyl-2,2'-spirobi[benzo-1,3,2-oxazaphospholines]

Chloromethylphosphonic dichloride reacts with o-aminophenol in the presence of triethylamine to form 2-chloromethyl-1,3,2-benzoxazaphospholine 2-oxide and 2-chloromethyl-2,2'-spirodi[1,3,2-benzoxazaphospholine] in a 1 : 1 ratio. 3-Diethylaminomethyl-2-ethoxy-1,3,2-benzoxazaphospholine reacts with o-aminophenol to form 2-diethylaminomethyl-2,2'-spirodi[benzo-1,3,2-oxazaphospholine]. The crystal and molecular structures of the synthesized spirophosphoranes were determined by single crystal X-ray diffraction.     

A study of the Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one derivatives

Summary The Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 a) gave 7-hydroxy-8-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (3 a) and 2,3-dihydro-2,6-diphenyl-3-methyl-(7H)furo[2,3-h]-1-benzopyran-7-one (7 a). 2-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 b) afforded4 b and7 b. 8-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (12) gave only the alkali soluble product 7-hydroxy-8-methyl-6-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (13).3 a,4 b, and13 were further cyclized in acidic medium to9 a,10 b, and14 followed by dehydrogenation.This paper is dedicated to Dr. F. M. Dean, Department of Organic Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool, U. K., on his retirement     

Synthesen von Heterocyclen, 130. Mitt.: Über das Glomerin und das Arborin

Zusammenfassung Es werden einstufige Synthesen desGlomerins (2) [1,2-Dimethyl-4(1H)-chinazolinon] und desArborins (3) [1-Methyl-2-benzyl-4(1H)-chinazolinon] bekanntgegeben.

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Syntheses of heterocycles, CXXX: Glomerine and arborine

A one step synthesis ofglomerine (2) [1.2-dimethyl-4(1H)-quinazolinone] andarborine (3) [1-methyl-2-benzyl-4(1H)-quinazolinone] is described.

     

Notiz zur Struktur des Umsetzungsproduktes von 4-Isothiocyanato-4-methyl-2-pentanon mit Hydrazin —Über das 2,4,5,6-Tetrahydro-5,5,7-trimethyl-3H-1,2,4-triazepin-3-thion

On reaction of 4-isothiocyanato-4-methyl-2-pentanone (1) with hydrazine 2,4,5,6-tetrahydro-5,5,7-trimethyl-3H-1,2,4-triazepine-3-thione (4 a) is formed not 1-aminodihydro-2(1H)-pyrimidinethione (3 a) [1-aminodihydro-2-pyrimidinethiol (2 a)].     

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).     

Acetylenchemie, 14. Mitt.: PTC-Umsetzung von 9(10H)-Acridinon mit 3-Chlor-3-phenyl-1-propin und 3-Brom-1-phenyl-1-propin

Summary Reaction of 9(10H)-acridinone (2) with 3-chloro-3-phenyl-1-propyne under PTC conditions affords 1-methyl-2-phenyl-6H-pyrrolo[3,2,1-de]acridin-6-one (1 b), 10-(2-chloro-1-methyl-2-phenyl-ethenyl)-9(10H)-acridinone (4), 10-(3-phenyl-1-propynyl)-9(10H)-acridinone (7), and 10-(4-methylene-2,3-diphenyl-2-cyclobuteneylidenemethyl)-9(10H)-acridinone (5). The structure of the last compound which crystallizes in the triclinic system with the space group , was confirmed by X-ray diffraction. Under the same conditions 10-(3-phenyl-2-propynyl)-9(10H)-acridinone (3) and 10-(3-phenyl-1-propynyl)-9(10H)-acridinone (6) were obtained from 9(10H)-acridinone (2) and 3-bromo-1-phenyl-1-propyne.

     

Decarboxylation of α-Amino Acids Containing Two and Three Stereogenic Centers: A Simple One-Step Procedure to Prepare two Optically Active β-Amino Alcohols and a Bicyclic Pyrrolidine Derivative

The decarboxylation of L-threonine (2S,3R)-1, L-hydroxyproline (2S,4R)-2 and D-2-azabicyclo[3.3.0]octan-3-carboxylic acid (1R,3R,5R)-5 yield in a simple one-step procedure the corresponding optically active β-amino alcohols (R)-3 and (R)-4 and the bicyclic pyrrolidine derivative (1R,5R)-6 in 72–82% yield and >99% ee.     

Enantiodivergence in the reduction of α-methyl and α-halomethyl enones by microorganisms

Enones (Z)-3-methyl-(Z)-3-chloromethyl- and (Z)-3-bromomethyl-4-R-3-buten-2-one (R = n-pentyl, phenyl, 2′- and 4′-chlorophenyl, 3′- and 4′-nitrophenyl, 4′-methoxyphenyl) were synthesized and subjected to reduction by the microorganisms Saccharomyces cerevisiae andGeotrichum candidum. Whereas the bioreduction of 3-methy-4-R-3-buten-2-ones afforded the corresponding (S)-4-R-3-methybutan-2-ones, the bioreduction of 3-chloromethyl- and 3-bromomethyl-4-R-3-buten-2-ones afforded the corresponding (R)-4-R-3-methybutan-2-ones.     

Preparation and Structure of (E)-1-(3′-Hydroxy-2-Furanyl)-3-(3″-Hydroxy-4″-Methoxyphenyl)-2-Propen-1-One

Abstract

A facile procedure is presented for the synthesis of (E)-1-(3′-hydroxy-2′-furanyl)-3-(3″-hydroxy-4″-methoxyphenyl)-2- propen-1-one (6). Galactosylisomaltol (1) was condensed with isovanillin (2) under strong alkaline conditions at 25 [ddot]C to form (E)-1-(3′-O-β-D-galactopyranosyloxy-2′-furanyl)-3-(3″- hydroxy-4″-methoxyphenyl)-2-propen-1-one (4). (E)-1-(3′-hydroxy-2′-furanyl)-3-(3″-hydroxy-4″-methoxyphenyl)-2-propen-1-one (6) was obtained by acid hydrolysis of 4 in a 53.9% yield. This hetero-cyclic 2-propen-1-one was characterized on the basis of spectral data (IR and ¹H NMR), physicochemical properties, and conversion to a mono-O-acetyl derivative.     

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).

     

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.

     

Candidate Trail Attractants of Reticultermes lucifugus: Stereoselective Syntheses of (3Z, 6E,BE)-(3Z, 6E, 8Z)-and (3Z, 6Z, 8Z)-3,6,8 -Dodecatrien-1-OL1

Stereoselective syntheses on a gram scale of (3Z,6E,8E)-, (3Z,6E,8Z)-and (3Z,6Z,8Z)-3,6,8-dodecatrien-1-ol, 8, 9 and 10, respectively, are described. A key step of the synthesis of 8 consisted of a copper-mediated coupling reaction between 4-(2-tetrahydropyranyloxy)-1-butynylmagnesium bromide (15) and the mesyl ester of (2E,4E)-2,4-octadien-1-ol (14). A similar copper-mediated reaction between 15 and the mesyl ester of (E)-2-octen-4-yn-1-ol (19) was used to construct the C-12 carbon skeleton of 9. On the other hand, the synthesis of 10 was based on a palladium-promoted reaction between (Z)-1-bromo-1-pentene (23) and the organozinc bromide derived from 3,6-heptadiyn-1-yl acetate (27).     

A new diarylheptanoid and a new diarylheptanoid glycoside isolated from the roots of Juglans mandshurica and their anti-inflammatory activities

A new diarylheptanoid, (2S,3S,5S)-2,3,5-trihydroxy-1,7-bis(4-hydroxy- 3-methoxyphenyl)heptane (1), and a new diarylheptanoid glycoside, (2S,3S,5S)-2,3-dihydroxy-5-O-β-d-xylopyranosyl-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)heptane (2), together with three known compounds, rhoiptelol C (3), rhoiptelol B (4) and 3′,4″-epoxy-2-O-β-d-glucopyanosyl-1-(4-hydroxyphenyl)- 7-(3-methoxyphenyl)heptan-3-one (5) were isolated from the roots of Juglans mandshurica (Juglandaceae). The structures of compounds 1 and 2 were identified based on HR-ESI-MS, 1D and 2D NMR spectroscopic methods. Compounds 1–5 were assayed for their inhibitory effects on the production of NO, TNF-α and IL-6 in LPS-stimulated RAW264.7 cells.     

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.     

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.