The synthesis of cypridina etioluciferamine and the proof of structure of cypridina luciferin

An unambiguous synthesis of Cypridina etioluciferamine was accomplished in order to prove the structure of this important bioluminescent natural product. Several 2-aminopyrazine 1-oxides were synthesized in order to establish a spectroscopic method for determining the placement of substituents on the pyrazine nucleus of Cypridina etioluciferamine. Titanium tetrachloride was used to improve the yields of these compounds; for example, the yield of 2-amino-3-methyl-5-phenylpyrazine 1-oxide (19) from reaction of phenylglyoxal 1-oxime and α-aminopropionitrile was raised from 3% to 51% by the use of titanium tetrachloride. The pyrazine ring proton is found at τ 1·37 (DMSO-d₆). The isomeric 2-amino-3-methyl-6-phenylpyrazine 1-oxide (22) was similarly prepared and its pyrazine ring proton is found at τ 2·18. This large difference (0·81 ppm) in chemical shift was used to determine whether a 2-aminopyrazine 1-oxide was 5- or 6- substituted. Prepared in an analogous fashion were 2-amino-5-(indol-3-yl)-3-methylpyrazine 1-oxide (23) and 2-amino-5-(indol-3-yl)-3-(3-phthalimidopropyl)pyrazine 1-oxide (16). The structures of these compounds were verified by NMR spectroscopy. By treatment with Raney nickel and hydrogen gas, then 100% hydrazine hydrate, 16 was converted to 2-amino-3-(3-aminopropyl)-5-indol-3-ylpyrazine (5), isolated as the dihydrochloride. This compound, with the indole moiety definitely placed at C-5, is identical with Cypridina etioluciferamine dihydrochloride (IR, UV, TLC). These results show that the structures of Cypridina etioluciferamine and luciferin are correct as published.     

Barbatusin and cyclobutatusin,two novel diterpenoids from coleus barbatus bentham

The structure of three diterpenoids from Coleus barbatus, Bentham (Labiatae) having a spirocyclopropyl side chain have been determined: they are barbatusin (1a), 3β-hydroxy-3-deoxybarbatusin (2) and cyclobutatusin (3a). The structures of 1a and 3a were established by X-ray diffraction analysis, and the latter compound has been shown to have an unusual 4-membered ring produced by a bond across C(1) to C(11). Chemical transformations and interconversions are presented, together with spectroscopic studies.     

Meloslines A and B,two novel indole alkaloids from Alstonia scholaris

An unprecedented indole alkaloid melosline A (1), with 6/5/6/6 tetracyclic ring skeleton, together with a new alkaloid melosline B (2) and one known compound (3) were isolated from the leaves and twigs of Alstonia scholaris. The new structures were elucidated by comprehensive spectroscopic analysis. The absolute configuration of compound 1 was confirmed by comparison of experimental data with calculated electronic circular dichroism (ECD). Compound 1 exhibited moderate cytotoxicity against MCF-7 cancer cell lines.     

Synthesis and crystal structure analysis of 2-(4-fluorobenzyl)-6-phenylimidazo[2,1-b][1,3,4]thiadiazole and its chlorophenyl derivative

Preparations of 2-(4-fluorobenzyl)-6-phenylimidazo[2,1-b][1,3,4]thiadiazole (3a) and its chlorophenyl derivative (3b) are described. Preliminary analysis was done spectroscopically by means of ¹H NMR, ¹³C NMR spectra, mass spectra and elemental analyses. Further the structures were confirmed by X-ray crystal structure analyses. The compound (3a) has crystallized in a triclinic P-1 space group with three independent molecules in the asymmetric unit, while the compound (3b) belongs to P2₁/c space group with one molecule in the asymmetric unit. The molecule (3b) differs from molecule (3a) by the presence of chlorine substituent. Additionally, the imidazo-thiadiazole entity is as usual planar. Intramolecular C–H⋯N hydrogen bonding between the imidazole and the phenyl ring of the molecule can be observed in (3a) & (3b). The molecules of (3a) are linked into two dimensional supramolecular hexagonal hydrogen bonded network sustained by C–H⋯F interaction, while those of (3b) are linked by bifurcated C–H⋯N interactions. Further, the molecular packing of both the compounds is stabilized by π–π stacking interactions between the benzene and imidazo-thiadiazole ring systems.     

Two significantly different conformations in crystal: formation of a molecular dimer governed by cation-π interactions

Two significantly different conformations were observed in crystal of 1, which form an unsymmetrical molecular dimer governed by cation-π interactions between a pyridinium cation and a phenyl ring, whereas compound 2 forms a head-to-tail type of dimer.     

A new synthetic method of 1α-hydroxy-7-dehydrocholesterol

Cholesta - 1,4,6 - trien - 3 - one (1) was converted to 3β - hydroxycholesta - 1,5,7 - triene (3) via the deconjugation procedure using t-BuOK in DMSO followed by the subsequent reduction with Ca(BH₄)₂. The compound (3) readily reacted with 4-phenyl-1,2,4-triazoline-3,5-dione to yield the corresponding 1,4-addition product (4). Epoxidation of 4 with m-chloroperbenzoic acid resulted in the formation of the 1α,2α-epoxide (5) and the 1β,2β-epoxide (6) in the ratio 2:3. Reduction of 5 with LAH under reflux in THF afforded the titled compound (7). The same reduction of 6 gave 2β-hydroxy- and 1β - hydroxy - 7 - dehydrocholesterol (8 and 9) in the ratio 8:1.The compound (4) can be obtained in 25% yield from 1 without any purification of the intermediate compounds; cholesta - 1,5,7 - trien - 3 - one (2, a very unstable compound) and 3. Since 1 is obtained readily from cholesterol in high yield, the present study provides a simple and efficient synthetic method of 1α-hydroxycholecalciferol and is reasonably expected to be applicable in the synthesis of 12,25-dihydroxycholecalciferol and the other metabolites of vitamin D₃.     

Isolation,tentative identification,and synthesis studies of the volatile components of the hairpencil secretion of the monarch butterfly

The major volatile components of the hairpencil secretion of the male monarch butterfly have been identified as benzyl caproate and either 1, 5, 5, 9-tetramethyl-10-oxabicyclo[4.4.0]-3- decen-2-one(1), or 2, 2, 6, 8-tetramethyl-7-oxabicyclo[4.4.0]-4-decen-3-one(2). One sequence designed to synthesize 1 yielded two isomeric products of structure 1 whose spectra are very similar to each other but distinctly different from those of the natural product; this sequence also yielded a tricyclic ketal (9). A second sequence gave two epimeric spiro compounds (12) and a third sequence gave a [4.3.0] ring system (14).     

Synthesis and antibacterial activity of some novel thieno[2,3-c]pyridazines using 3-amino-5-phenyl-2-ethoxycarbonylthieno[2,3-c]pyridazine as a starting material

3-Amino-5-phenyl-2-ethoxycarbonylthieno[2,3-c]pyridazine (6) was prepared by reaction of 4-cyano-6-phenylpyridazine-3(2H)-thione (4) with ethyl chloroacetate in the presence of sodium ethoxide. Hydrazinolysis of compound 6 yielded the corresponding carbohydrazide, (9) which on treatment with acetylacetone and ethyl acetoacetate produced the novel thieno[2,3-c]pyridazines (10 and 11). Treatment of compound 9 with nitrous acid yielded the corresponding carboazide (13), which upon boiling in toluene furnished imidazo[4′,5′:4,5]thieno[2,3-c]pyridazine (15). Pyrimidothienopyridazines (16–18) were achieved by cyclocondensation of compound 9 with some reagents, namely acetic anhydride, formic acid, and triethyl orthoformate. The newly synthesized compounds were confirmed by elemental analyses and spectral data. The antibacterial activities of the new compounds were also evaluated.     

Dieckmann cyclisation of some β,γ-unsaturated dimethyl esters—I

Dieckmann cyclisation of some β,γ-unsaturated diesters of the indane series gives as major product of the ring closure the compound derived from the more carbanion formed under standardised reaction conditions. The methyl β-(2-methoxycarbonylmethyl-7-methylinden-3-yl)propionate (2) on Dieckmann ring closure, gives 1-methoxycarbonyl-2-oxo-1,2,3,4-tetrahydro-8-methylfluorene (7) and not the isomeric 3-methoxycarbonyl-2-oxo-1,2,3,4-tetrahydro-8-methylfluorene (6) reported earlier.     

In vitro antioxidant properties of new thiazole derivatives

A series of novel N2-[2-chloro-4(3,4,5-trimethoxy phenyl azetidin-1-yl]-N4-(substituted aryl)-1,3-thiazole-2,4-diamine (4a–g) were synthesized starting from 3,4,5-trimethoxy benzaldehyde thiosemicarbazone (1). The compound (1) was obtained by condensing 3,4,5-trimethoxy benzaldehyde with thiosemicarbazide in methanol. 3,4,5-Trimethoxy benzaldehyde thiosemicarbazone (1) on treatment with chloracetyl chloride afforded 4-chloro-[2-(3,4,5-trimethoxy benzylidine) hydrazinyl]-1,3-thiazole (2). Compound (2) was reacted with chloracetyl chloride and triethylamine to obtain the corresponding 4-chloro-N-[2-chloro-4(3,4,5-trimethoxy phenyl) azetidin-1-yl]-1,3-thiazole-2-amine (3). Various substitutions on compound 3 with secondary amines yielded series of compounds (4a–g). The newly synthesized compounds were characterized by IR, ¹H NMR, elemental analysis and mass spectral studies. All the compounds were screened for their in vitro antioxidant properties. The IC₅₀ values of compounds 3 and 4a–g revealed that some of the synthesized compounds were showing potent antioxidant activity.     

1-Amino-adamantan als nucleophile substitutions-, additions- und ringspaltungskomponente : Antivirale wirkstoffe—VII

The ring cleavage occurring under the nucleophilic attack of 1-aminoadamantane (2) on s-triazine (1) leads to the formation of N,N′-bis-[1-adamantyl]-formamidine (5). 2 forms β-[2-furyl]-acrylic acid-[1-adamantyl]-amide (8) upon interacting with β-[2-furyl]-acrylic acid chloride (6). 8 exhibits remarkable antiviral activity.     

Biosynthesis of tylophorine and tylophorinine

Administration of 3,4-dihydroxyphenyl[2-¹⁴C] alanine to young Tylophora asthmatica plants revealed that ring B and carbon atoms C₉ and C₇ of tylophorine and tylophorinine are derived from dopa. Tracer experiments with 6,7-diphenylhexahydroindolizines (1–7) and (26) demonstrated that compound 1 is efficiently and specifically incorporated into tylophorine (13) and tylophorinine (16). Compounds (3), (4) and (26) were not metabolized by the plants to form (13) and (16) whereas (5) and (6) were utilized to yield (13) and (16). Compound (2) was very poorly converted into (13) and (16) and thus is not on the major biosynthetic pathway of (13) and (16).     

Synthesis,characterization and antimicrobial activity of novel sulphapiperazine containing arylazopyrazoles

Mannich reaction of benzotriazole (1), ethyl-4-amino benzoate (2) and formaldehyde in ethanol afforded 4-(1H)-benzotriazoyl methyl amino benzoate (3), which on treatment with hydrazine hydrate results in the 4-(1H)-benzotriazoyl methyl amino benzoyl hydrazide (4). This compound on condensation with pre-prepared various ethyl-2-substituted phenyl hydrazono-3-oxobutyrates (6a–h), furnished 1-(4-((1H-benzo[d][1,2,3]triazol-1-yl) methyl amino) benzoyl)-3-methyl-4-(2-(4-(4-alkylpiperazin-1-ylsulfonyl) phenyl) hydrazono)-1H-pyrazol-5(4H)-ones (7a–h). All these compounds (7a–h) were characterized by spectral studies. The compounds showed significant antimicrobial activity against various bacteria and fungi.     

Eucalyptals D and E,new cytotoxic phloroglucinols from the fruits of Eucalyptus globulus and assignment of absolute configuration

Two new phloroglucinols, named eucalyptals D (1) and E (2), along with a related known compound (euglobal-In-3, 3) were isolated from the fruits of Eucalyptus globulus. Their structures were established on the basis of extensive spectroscopic studies, revealing that they share a common 3,5-diformyl-isopentyl phloroglucinol unit, but each is instead coupled to a different sesquiterpenoid skeleton (aromadendrene in 1, cadinene in 2, and a spirosesquiterpene in 3). Compound 1 possessed an unusual seven-membered D ring with an ether bridge between C-2 of the aromadendrene moiety and C-2′ of the aromatic unit. The absolute configuration of the isolates was defined by the comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1–3 exhibited significant in vitro cytotoxicities against a few human cancer cell lines (Huh-7, Jurkat, BGC-823, and KE-97) using the CellTiter-Glo^TM luminescent cell viability assay method.     

New compounds from the roots of Coriaria nepalensis

One new sesquiterpene lactone possessing novel variations in the structure, corialactone E (1), one new neolignan, coriarianeolignan A (2), together with three known apocarotenoids (3-5) and one known neolignan (6), have been isolated from a CHCl₃ extract of the roots of Coriaria nepalensis.     

Comprehensive study towards the desulfonylation/desulfinylation of cis-3-functionalized 3-phenylsulfonyl/sulfinyl-β-lactams to access novel cis-3-monosubstituted-β-lactams

An inclusive study towards the stereospecific synthesis of novel cis-3-monosubstituted-β-lactams from cis-3-functionalized 3-phenylsulfonyl/sulfinyl-β-lactams is described. 3-Sulfinyl-β-lactams 5/5? successfully furnished stereospecific cis-3-monosubstituted-β-lactams 6, however 3-sulfonyl-β-lactams 2 failed to give the desulfurized product 6?. The final stereochemical and structural conformations of novel β-lactams were established by single crystal X-ray crystallographic study (5c). The cis configuration of the β-lactams 5/5? and 6 was assigned in relevance to E and C4-H and C3-H and C4-H respectively.     

Synthesis of new azetidinonyl/thiazolidinonyl quinazolinone derivatives as antiparkinsonian agents

Several 3-amantadinyl-2-[(2-substituted benzylidenehydrazinyl)methyl]-quinazolin-4(3H)-ones (5a–5l) were prepared by the reaction of 3-amantadinyl-2-hydrazinylmethyl substituted quinazolin-4(3H)-ones (4a–4b) with various substituted aromatic aldehydes. Cycloaddition of compounds (5a–5l) with thioglycolic acid in the presence of anhydrous zinc chloride yielded 3-amantadinyl-2-[((substitutedphenyl)-4-oxo-thiazolidin-3-yl)methylamino]-quinazolin-4(3H)-ones (6a–6l). Compounds 5a–5l on further reaction with chloro acetyl chloride in the presence of triethylamine gave 3-amantadinyl-2-[((substitutedphenyl)-3-chloro-2-oxo-azetidin-1-yl)methylamino]-quinazolin-4(3H)-ones (7a–7l). The compounds 5a–5l, 6a–6l and 7a–7l were screened for their antiparkinsonian activity. The most active compound was 6g i.e. 3-amantadinyl-6-bromo-2-[((3,4-dimethoxyphenyl)-4-oxo-thiazolidin-3-yl)methylamino]-quinazolin-4(3H)-ones. Structures of the newly synthesized compounds were established on the basis of elemental and spectral (IR, ¹H NMR and mass) analysis.     

One-dimensional structures of zinc(II) and cobalt(II) coordination complexes [Zn(NCS)2(PPz)]n and [CoCl2(PPz)]n (PPz=piperazine)

The reaction of Zn(NO₃)₂·6H₂O with PPz hexahydrate (PPz=piperazine) and NH₄SCN in CH₃OH afforded the complex [Zn(NCS)₂(PPz)]_n (1). The reaction of CoCl₂·6H₂O with PPz in CH₃OH afforded the complex [CoCl₂(PPz)]_n (2). The PPz ligand in 1 is coordinated to the metal centers through both nitrogen atoms to form a 1-D zigzag-chain structure and the distorted tetrahedral coordination geometry at each zinc center is completed by a pair of N-bonded thiocyanate ligands. Compound 2 has an analogous 1-D zigzag-chain structure containing terminal chloro ligands. Important NCSH---N hydrogen-bonding interactions in compound 1 and N---HCl---M and C---HCl---M hydrogen-bonding interactions in compound 2 play a significant role in aligning the polymer strands in the crystalline solid.     

Effect of solvent on the regioselective synthesis of spiropyrazoles

1,3-Dipolarcycloaddition reactions of 6-arylmethylene-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ones (1) with nitrilimines 3 were investigated in benzene and chloroform. The reaction products were 2′,4′,6,7,8,9-hexahydro-2′,4′,5′-triaryl spiro[benzocycloheptene-6(5H),3′(3H-pyrazol)-5-ones (4) or 2′,3′,6,7,8,9-hexahydro-2′,3′,5′-triaryl spiro[benzocycloheptene-6(5H),4′(4H-pyrazol)-5-ones (5). X-ray crystallographic analysis was carried out for compound 5b. It was found that the regioselectivity of the produced compounds was altered based on changing solvent type.     

Hochdruckversuche—IX: Die thermische isomerisierung von 1,2-diphenyl-3-methyl-cyclobuten-(1)-cis-3,4-dicarbonsäuredimethylester und 3,4-dimethyl-1,2-diphenyl-cyclobuten-(1)-cis-3,4-dicarbonsäuredimethylester

Dimethyl-1,2-diphenyl-3-methyl-cyclobutene-(1)-cis-3,4-dicarboxylate 2 leads in a thermal reaction to an equilibrium with (E, Z)-dimethyl-3,4-diphenyl-5-methyl-muconate (4). The equilibrium is shifted to the cyclic compound by pressure. Dimethyl-3,4-diphenyl-cyclobutene-(1,2-diphenyl-cyclobutene-(1)-cis-3,4-dicarboxylate (3) isomerizes thermally to (E, Z)-dimethyl-2,5-dimethyl-3,4-diphenylmuconate (6). Both reactions are accelerated by pressure. The activation volumes ΔV₀⁺ are given for each ringopening reaction.