Functionalized 2-azabicyclo[3.3.1]nonanes. III.1 reductive rearrangement of an hexahydro-2-oxopyrano[3,2-b]pyridine

Reduction of 5-benzoyl-8-methyl-2-oxo-3,4,4a,5,6,7-hexahydro-2H-pyrano[3,2-b] pyridine ($\text{1}$) with lithium aluminium hydride afforded (1R^*,5S^*,6R^*,9S^*)-2-benzyl-5-methyl-2-azabicyclo[3.3.1]nonane-6,9-diol ($\text{2}$).     

Action of tert-butyl azidoformate on the conjugate bases of 1,2,3,4-tetrahydro-9H-carbazole and other indole derivatives

tert-Butyl azidoformate ($\text{2}$) reacts with the conjugate bases of $\text{3a}$, $\text{7a}$, $\text{9}$ (R¹ = R² = CH₃), and $\text{9}$ (R¹ = CH₃, R² = H) to give products [$\text{4}$, $\text{8}$, $\text{12}$, and $\text{14}$, respectively] in addition to the expected N-(tert-butoxycarbonyl)indole derivatives.     

3-methylthio-1,2-dithiolylium salts : Reaction with 4-hydroxy-6-methyl-2H-pyran-2-one and 4-hydroxycoumarin

The reaction of 4- and 5-aryl-3-methylthio-1,2-dithiolylium iodides with 4-hydroxy-6-methyl-2$\text{H}$-pyran-2-one and 4-hydroxycoumarin has been studied. 4-Substituted salts yielded 3-aryl-7-methyl-2-thioxo-2$\text{H}$,5$\text{H}$-pyrano [3,2-c]pyran-5-ones and 3-aryl-2-thioxo-2H,5H-pyrano[3,2-c]benzo[e]pyran-5-ones, respectively, whereas 5-substituted salts gave rise to 3-(5′-aryl-1′,2′-dithiol-3′-ylidene)-6-methyl-2$\text{H}$-pyran-2,4-diones and 3-(5′-aryl-1′,2′-dithiol-3′-ylidene)-2$\text{H}$-benzo [b]-pyran-2,4-diones.     

Functionalized 2-azabicyclo[3.3.1]nonanes. IV. synthesis of the indolo[3,2-f]morphan system.

A short route to the 2-azabicyclo[3.3.1]nonan-7-one system is described. Condensation of 4-piperidones with diethyl 2-oxopropylphosphonate, followed by catalytic hydrogenation furnished the corresponding piperidylpropanones $\text{6}$ which were cyclized with mercuric acetate in acetic acid to the target target bicyclic ketones $\text{1}$. The Fischer indole synthesis from $\text{1}$$\text{a}$ afforded regioselectively the indole [3,2-f]morphan $\text{2}$, a new heteromorphan type.     

Ring transformation of 4-oxo-1,6,7,8-tetrahydro-4H-pyrido[1,2-a]-pyrimidine-3-carboxamide

The title compound /$\text{3}$/ may be transformed into the 3-/methylaminomethylene/--2,3,6,7,8,9-hexahydro-4H-pyrido[1,2-a]pyrimidine-2,4-dione /$\text{5}$E, $\text{5}$Z/ which is in equilibrium with the 1,2,3,6,7,8-hexahydro tautomer /$\text{8}$E, $\text{8}$Z/ in DMSO-d₆.     

Studies in the chemistry of erythrina alkaloide derivatives—II : Synthesis and stereochemistry of decahydro-3-methyl-6H-pyrido]2,1-i]indole

1,2,3,4,7,7a,8,9,10,11-Decahydro-3-methyl-6$\text{H}$-pyrido[2,1-i]indole was prepared as an example of an erythrinane derivative lacking the aromatic moiety. The stereochemical structure of this compound and its 6-oxo derivative were found to be predominantly cis A/B, trans B/C, axial CH₃ and cis A/B, axial CH₃, respectively.     

An efficient synthesis of (7S,10R)-2-bromo-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole: application in the preparation and structural confirmation of a potent 5-HT6 antagonist

(7S,10R)-5-Methyl-2-((3-(trifluoromethyl)phenyl)sulfonyl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole 1a is a potent 5-HT₆ antagonist (h5-HT₆ K_i = 1.5 nM) which is derived from an epiminocyclohept[b]indole scaffold. In order to synthesize 1a on a multi-gram scale to support advanced biological testing, an efficient chiral resolution of the intermediate tert-butyl 2-bromo-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-11-carboxylate 2 was developed. After derivatizing 2 with (1R)-(?)-menthyl chloroformate it was found that a single diastereomer 7a could be isolated by selective precipitation from n-hexane. The absolute stereochemistry of 7a was determined by X-ray crystallography and the structure was confirmed as (7S,10R)-tert-butyl 2-bromo-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-11-carboxylate. Removal of the chiral auxiliary under basic conditions afforded intermediate 2a in >99% enantiomeric purity and with 80% yield based on recovery from the racemic compound 2. Intermediate 2a was used successfully to synthesize 5-HT₆ antagonist 1a on a multi-gram scale.     

Photo-oxygenations of 1H-azepine derivatives isolation and characterization of the [6+2] cycloaddition product

The reactions of 1H-azepine derivatives ($\text{1a-b}$ and $\text{4}$) with singlet oxygen gave the [6+2] cycloadducts ($\text{2a-b}$) and the [4+2] cycloadducts ($\text{3a-b}$ and $\text{5}$). The thermal and base-catalyzed rearrangements of the oxygen-adducts were investigated.     

Condensed cyclic and bridged-ring systems : part 12: A novel synthetic route to 4-p-methoxyphenyl-bicyclo[ 2.2.2 ]octan-2-ones and some bicyclo [ 3.2.1 ] octane derivatives by acid-catalyzed intramolecula

The efficacy of a new acid-catalyzed intramolecular C-alkylation has been demonstrated by the synthesis of 1-methyl-4-$\text{p}$-methoxyphenylbicyclo [2.2.2] octan-2-one ($\text{5}$) and 4-$\text{p}$-methoxyphenylbicyclo [2.2.2] octan-2-one ($\text{6}$) from easily accessible starting materials. The carbinol $\text{20}$, derived from $\text{5}$, undergoes facile rearrangement leading to 1-$\text{p}$-methoxyphenyl-4-methyl bicyclo [3.2.1] oct-3-ene ($\text{22}$), which has been transformed to $\text{endo}$-1-$\text{p}$-methoxyphenyl-4-methylbicyclo [3.2.1] octan-3-one ($\text{25}$).     

Palladium-catalyzed cyclization reactions of 3-propargylthio 1,2,4-triazin-5(2h)-ones to thiazolo-1,2,4-triazinones

Selective transformation of 3-propargylthio-1,2,4-triazin-5(2H)-ones ($\text{1}$) to 6-methylene-6,7-dihydro-4H-thiazolo[2,3-c][1,2,4]-triazin-4-ones ($\text{2}$) and 3-methylene-2,3-dihydro-7H-thiazolo[3,2-b]-[1,2,4]triazin-7-ones ($\text{3}$) is performed under the conditions of Pd(II) salt or sodium hydroxide catalysis, respectively.     

Copper(II) in organic synthesis. IV Reaction of the copper(II) acetate complex of isatin-3-arylhydrazones with dimethyl acety-lenedicarboxylate.

The copper(II) acetate complex of isatin-3-phenylhy-drazone (2a) reacted with dimethyl acetylenedicarboxylate (DMAD) by two competitive pathways: a Cu⁺⁺ oxidation of the ligand and a [2+2] cycloaddition. The former reaction gave 3-car- benindolin-2-one (13) which reacted with DMAD in a l,3-dipolar cycloaddition, to give 3a. This was synthesized by an independent route. The phenyl radical, generated in the same process, was trapped by three DMAD and gave $\text{4a}$. The [2+2] cycloaddition gave a spiro adduct 10 which, by electrocyclic ring opening and intramolecular cyclization, allowed isolation of a pyridazino [3,4-b] indole (|5a). The reaction was performed on $\text{p}$-chlorophe-nylhydrazone 1b and the structure of 5b was demonstrated by X-ray analysis. A rationalization of the reactivity was attempted in terms of MO interactions of the reactants.     

Bridgehead nitrogen heterocycles from 2,4,6-triphenyl- pyrylium cation and thiosemicarbazide or thiocarbohydrazide

2,4,6-Triphenylpyrylium with thiosemicarbazide and thiocarbohydrazide, gives 2-pyrazolines $\text{3a}$ and $\text{3b}$ which undergo cyclization yielding pyrazolo(1,5-c]pyrimidine 5 and pyrazolo [2,3-d]-1,2,4-triazepine $\text{7}$ derivatives, respectively. Reaction of $\text{7}$ with phenacyl bromides gave 1,3-thiazolo[3,2-b]pyrazolo [2,3-d]-1,2,4-triazepin-4-iums $\text{10}$. Compound $\text{3a}$ on treatment with phenacyl bromides gave 1-(4'-aryl-thiazol-2'-yl)-2-pyrazoline derivatives $\text{6}$. Compound $\text{3b}$ reacts with acyl chlorides to give pyrazolo[1,5-c]pyrimidine derivatives $\text{14}$, and with aromatic aldehydes giving the 2-(Δ^2'1 pyrazolin-1-yl)-5-aryl-1,3,4-Δ²-thiadiazolines $\text{12}$ which were easily converted to the corresponding 2-(Δ²-pyrazolin-1-yl)-5-aryl-1,3,4-thiadiazoles $\text{13}$.     

Synthesis of the natural enantiomers of ascochlorin,ascofuranone and ascofuranol

Three fungal metabolites with a common structural feature as prenylated phenols were synthesized in their naturally occurring and optically active forms: ascochlorin [(2'$\text{E}$,4'$\text{E}$,1'$\text{R}$,2'$\text{R}$,6'$\text{R}$)-(-)-5-chloro-2,4-dihydroxy-6-methyl-3-[5'-(1',2',6'-trimethyl-3'-oxo-cyclohexyl)-3'-methyl-2', 4'-pentadienyl] benzaldehyde], ascofuranone [(2'$\text{E}$,6'$\text{E}$,1'$\text{S}$)-(-)-5-chloro-2, 4-dihydroxy-6-methyl-3-[7'-(3',3'-dimethyl-4'-oxo-2'-oxacyclopentyl)-3',7'-dimethyl -2', 6'-heptadienyl] benzaldehyde] and ascofuranol [(2'$\text{E}$,6'$\text{E}$,1'$\text{S}$,4'$\text{S}$)-(-)-5-chloro-2,4-dihydroxy-6-methyl-3-[7'-(3', 3'-dimethyl-4'-hydroxy-2'-oxacyclopentyl)-3', 7'-dimethyl-2',6'-hepta-dienyl]benzaldehyde ]. (+)-Ascofuranone and (+)-ascofuranol were also synthesized. By the present synthesis the absolute configuration of the natural (-)-ascofuranol was established as (1'$\text{S}$,4'$\text{S}$).     

En route to hexaaza-kekulene

As synthetic precursors of hexaaza-kekulene 1 the dibenzo[$\text{b,j}$]= [1,10] phenanthroline systems 2, 3, 4, 5 and 6 were prepared. From 6 via 7 a product was obtained for which the dodecahydrohexaaza-kekulene structure 8 is suggested on the basis of ¹H-NMR comparison with the dipyrido[3,2-$\text{c}$;=2′,3′-$\text{h}$]acridine (14) for which two syntheses are reported.     

Five-membered 2,3-dioxo heterocycles: LXII. Reaction of 3-aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones with N,N′-dihydroxycyclohexane-1,2-diamine. Unusual rearrangement in the spiro[quinoxaline-2,2′-pyrrole] system

3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones reacted with N,N′-dihydroxycyclohexane-1,2-diamine to give 3-aroyl-1′,4,4′-trihydroxy-1-(2-hydroxyphenyl)-4a′,5′,6′,7′,8′,8a′-hexahydro-1′H-spiro[pyrrole-2,2′-quinoxaline]-3′,5(1H,4′H)-diones which underwent rearrangement into 1′-aroyloxy-4,4′-dihydroxy-1-(2-hydroxyphenyl)-4a′,5′,6′,7′,8′,8a′-hexahydro-1′H-spiro[pyrrolidine-2,2′-quinoxaline]3′,4,5(4′H)-triones via [1,4]-migration of the aroyl group. The product structure was proved by X-ray analysis.     

The octant rule. XVI1. COnformation and circular dichroism of syn and anti 2-methylbicyclo[3.1.0]hexan-3-ones,thujone and isothujone

(lS,5S)-exo-2(R)-Methylbicyclo[3.1.0]hexan-3-one ($\text{1}$) and (lS,5S)-endo-2(S)-methylbicyclo[3.1.0]hexan-3-one (2) were synthesized and their circular dichroism (CD) spectra run. Conformational analysis based on molecular mechanics calculations and Karplus equation analyses of vicinal H¦H NMR coupling constants indicate boat-like sofa conformations for both $\text{1}$ and $\text{2}$, with very little ring distortion from the symmetry of the parent bicyclo[3.1.0]hexan-3-one. The lone dissymmetric ψ-axial and ψ-equatorial methyl groups of $\text{1}$ and $\text{2}$, respectively, are both octant consignate. The natural product analogs of $\text{1}$ and $\text{2}$, (?)-3-isothujone ($\text{3}$) and (+)-3-thujone ($\text{4}$) were prepared and examined similarly. Their α-methyl perturbers dominate the CD n-π^★ Cotton effects.     

v-Triazolines. part XXI. Spiro[bicyclo[2.2.1]hept-2-ene[54']1',2'.s'-triazole]derivatives from cyclopentadiene and 5-amino-4-methylene-v-triazolines

1R^*, 4R^*, 5S^*, 5'S^*-5'-Amino-1'-(4-nitrophenyl)-4',5'-dihydrospiro[bicyclo [2.2. 1]hept-2-ene[5.4]-1',2',3'-triazoles]$\text{2}$ have been obtained both by ?4 +2]-cycloaddition of cyclopentadiene to amino-methylene-1-(4-nitrophenyl)-4,5-dihydro-v-triazoles $\text{1}$ and by [3+2]-cycloaddition of 4-nitrophenylazide to 5-aminomethylene-2-norborenes $\text{4}$. The configuration has been fully established by X-ray crystallographic analysis. The course of the cycloaddition and the thermal behaviour of $\text{2}$ are discussed.     

New terpenoid aldehydes from Kigelia pinnata: crystal structure of pinnatal

From the root bark of Kigelia pinnata (Bignoniaceae) two aldehydes, norviburtinal(6-formylcyclo-penta[c]pyran) and pinnatal, 11-formyl-2, 3, 3a, 5, 10, 10a, 11, 11a-octahydro-8-hydroxy-3, 11-dimethyl-3, 10a-epoxy-1$\text{H}\text{-}$-cyclopent[b]anthracene-5, 10-dione, have been isolated. The structures were determined by spectroscopic methods, and X-ray crystallographic analysis of pinnatal.     

Isolation and synthesis of vobparicine,a novel type dimeric indole alkaloid

From the rootbark of Tabernaemontana chippii a novel antimicrobially active dimeric indole alkaloid was isolated which was assigned structure $\text{1}$ on the basis of spectroscopic evidence and its synthesis.     

The photo cycloaddition of alkenes to s-triazolo[4,3-b] and [2,3-b]pyridazines

s-Triazolo[4,3-b]pyridazine (I) reacted with cyclohexene under the influence of ultraviolet light to yield 4a,5,7,8,8a,9-hexahydro-9-methylene-6H-s-triazolo[1,5-a]indole (IV) and 9-cyanomethyl-4a,5,7,8,8a,9-hexahydro-6H-s-triazolo[1,5-a]indole (V). These products were formed by the addition of the alkene to the 1,8 positions of I with a concurrent cleavage of the N₄? N₅ bond. Similar additions were observed with cyclopentene and 2,3-dimethyl-1,3-butadiene. The isomeric s-triazolo[2,3-b]pyridazine (III) reacted with cyclohexene to form an isomer of IV, 4a,5,7,8,8a,9-hexahydro-9-methylene-6H-s-triazolo[4,3-a]indole (XV) and two [2 + 2] cycloadducts (XVI and XVII).