Saturated heterocycles. Part 216 . Synthesis,structure and ring opening of trans-perhydro-1,4-benzoxazepin-3-one derivatives

trans-Perhydro-1,4-benzoxazepin-3-ones 2a-c were synthesized and transformed to condensed-skeleton perhydro-trans-1,4-benzoxazepines 3a,b , the thiones 4a,b , the urea derivatives 5a,b , and N-acylated compounds 6a-e . Compounds 6b,d were ring-opened by hydrochloric acid in ethanol to yield trans-2-(1-carbethoxyethoxy)-1-acylaminomethylcyclohexane derivatives 7b,d . The ¹H- and ¹³C-nmr investigation and X-ray analysis of 5b and 6c,d proved that the expected N-acylated derivatives were formed and that both rings of the trans anellated compounds have a chair conformation.     

λ-radiolysis of mitomycin c derivatives

The λ-Radiolysis reactions of mitomycin C ( 1 ) and its derivatives were studied in the hope of developing a radiation-induced drug (RID). The λ-radiolysis reactions were carried out in aqueous solutions under the condition where hydrated electron (e^?_aq) was generated as a principal reactive species. The competitive λ-radiolysis studies revealed that the rate constants for the reactions of 1 with e^?_aq at room temperature was 3.6 × 10¹⁰ dm³ mol^?1s^?1. Among mitomycin C derivatives, the 5H-6-alkoxyimino derivatives 11 and 12 , and compound 13 in which ring A of 1 has the 4-hydroxy-6-hydroxyimino structure cleaved to give 1 . The mechanic aspect of these λ-radiolysis reactions is discussed.     

Recent advances in the synthesis of cyclodextrin derivatives under microwaves and power ultrasound

We describe improved syntheses of CD derivatives, like 6^I-monotosyl, 6^I-monoazido-6^I -monodeoxy, 6^I-monoamino-6^I-monodeoxy-βCD and 2^I-O-mono(methylamino)alkyl-βCDs, that were carried out under US or MW, to great advantage in terms of yield, purity and reaction time. In the search for more efficient procedures to prepare monosubstituted CDs, we applied MW and/or US to some fundamental preparations such as those of 6^I-amino-6^I-deoxy-βCD and a series of 2-monoaminomethyl-βCD derivatives.     

4,5,6,7-Tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acids (spinacines)

New derivatives of the naturally occurring amino acid 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid (spinacine) are reported. These include amide, ester, 5-alkyl and acyl, and regiospecific N^im-alkyl and aralkyl derivatives. Synthesis via the Pictet-Spengler reaction on N^im-substituted histidines is described. Cyclic hydantoin derivatives of spinacines are included.     

1,4,4a,10b-Tetrahydro-N,N-dimethyl-4-phenanthridinamines and 1,4,4a,5,6,10b-hexahydro-N,N-dimethyl-4-phenanthridinamines

Synthetic procedures to prepare the title compounds are described. Diels-Alder cycloaddition of β-nitrostyrene derivatives 5 to N,N-dimethyl-1,3-butadien-1-amine, 6 , gave 5-aryl-N,N-dimethyl-6-nitro-2-cyclohexen-1-amines 7. Reduction of 7 with zinc in acetic acid gave the diamino derivatives 8 . Schotten-Baumann acylation of 8 gave amides 9 . Treatment of 8 with alkyl isocyanates gave the aminourea derivatives 10 . Bischler-Napieralski cyclodehydration procudure of 9 and 10 gave 1,4,4a,10b-tetrahydrophenanthridinamines 3 and N⁶-alkyl-1,4,4a,10b-tetrahydro-N⁴,N⁴-dimethyl-4,6-phenanthridinediamines 11 , respectively. Condensation of diamines 8 with aryl aldehydes under azeotropic conditions gave imines 12 which on treatment with acids yielded 6-aryl-1,4,4a,5,6,10b-hexahydro-N,N-dimethyl-4-phenanthridinamines 4 . The stereochemistry of these materials is assigned from the proton magnetic resonance studies.     

Substituent Reactivity and Tautomerism of Isoguanosine and Related Nucleosides

The substituent reactivity and tautomerism of isoguanine nucleosides is studied. Benzoylation or tosylation of isoguanine nucleosides (pyridine, room temperature) yields the 2-benzoyl derivatives 7c, 11 , and 12 or the 2-tosyl compounds 13 and 14 . The isobutyrylation of the 6-amino group which did not occur under these conditions was induced in the presence of Me₃SiCl. In the absence of Me₃SiCl, the reactivity of isoguanine substituents decreases in the order from 2-oxo → 5′-OH → 3′-OH → 6-NH₂. From isoguanine nucleosides, the N¹-( 2b ), N³-( 17 ), N⁶-( 15a,b ), and 2-O-alkylated ( 3b ) derivatives were prepared. Their pK_a values were determined and the UV and ¹³C-NMR spectra compared with regard to the alkylation position. Also the tautomeric forms of isoguanine nucleosides were determined UV-spectrophotometrically in aqueous and nonaqueous solution. Isoguanosine ( 1a ), its 2′-deoxy analogue 1b as well as the N⁶-methyl- and 8-substituted derivatives form lactam tautomers in aqueous solution, whereas the lactim form is present in dioxane.     

N-Benzyl Derivatives of Leucine Esters

Leucine methyl and ethyl esters reacted with 3-bromobenzaldehyde and 4-chlorobenzaldehyde in anhydrous methanol in the presence of magnesium sulfate to afford the coresponding Schiff bases of the general formula (CH3)2CHCH2CH(COOR¹)N=CHR² [R¹ = CH3, C2H5, R²= 3-BrC6H4, 4-ClC6H4]. Their reduction with sodium tetrahydridoborate yielded N-benzyl derivatives (CH3)2CHCH2CH(COOR¹)NHCH2R², which were converted into N-acyl-N-benzyl derivatives (CH3)2CHCH2CH(COOR¹)N(COR³)CH2R²[R³= CH₃, C₆H₅].     

Synthesis of 32‐phenyl‐substituted methyl E/Z‐pyropheophorbide‐a's from methyl E/Z‐pyropehophorbide‐a 131‐ketoximes

Methyl E/Z‐pyropheophorbide‐a 13¹‐ketoximes 2a,b and their O‐acetyl derivatives 3a,b were oxidized with osmium(VIII) oxide to give aldehydes 4a,b and 5a,b , respectively. The Wittig reactions of the aldehyde chlorines 4a,b and 5a,b with benzyltriphenylphosphonium chloride were performed to form the corresponding methyl (3¹E/Z,13¹E/Z)‐3²‐phenylpyropheophorbide‐a 13¹‐ketoximes 6aa‐bb and their O‐acetyl derivatives 7aa‐bb ; hydrolysis of these ketoximes 6aa,ba and 6ab,bb in formic acid produced methyl (E/Z)‐3²‐phenylpyropheophorbide‐a's 8a,b .     

Pyrimidines,Part XXXI . Synthesis,reactions and properties of 6-acyl-1,3-dimethylpyrrolo[2,3-d]pyrimidine-2,4-diones

Acylations of 1,3-dimethyl- ( 1 ) and 1,3,7-trimethylpyrrolo[2,3-d]pyrimidine-2,4-dione ( 2 ) with anhydrides in the presence of trifluoroacetic acid proceed well to give in good yields the corresponding 7-acyl derivatives 3–11 . The 6-trichloroacetyl derivatives 5 and 6 are sensitive towards nucleophiles, which displace the trichloromethyl group easily by formation of the corresponding 6-carboxylic acid derivatives 12–23. The newly synthesized compounds have been characterized by elemental analysis, uv and ¹H nmr spectra and pK_a, determinations.     

Synthesis of quinazolino-1,3-benzothiazine derivatives

The ring-closure reactions of N-(3,4-dimethoxyphenylthiomethyl)-2-nitrobenzamide derivatives 5a,b with phosphoryl chloride gave 4-(2-nitrophenyl)-2H1,3-benzothiazine derivatives 7a,b , which on reduction yielded 4-(2′-aminophenyl)-3,4-dihydro-2H-1,3-benzothiazines 8a,b. Reaction of these compounds with phosgene led to a new heterocyclic ring system, 6H,8H-quinazolino[3,4-c][1,3]benzothiazine derivatives 9a,b. The structures of the title compounds were proved via their ir and nmr (¹H, ¹³C) spectra.     

Conformational Analysis of Hydroxymethyl Group of D-Mannose Derivatives Using (6S)- and (6R)-(6-2H1)-D-Mannose

ABSTRACT

D-Mannose derivatives stereospecifically deuterated at C-6 were synthesized and the unequivocal ¹H NMR assignments of H-6proS and H-6pro R were made. The preferred conformation of the hydroxymethyl groups of these compounds are discussed.     

α-Cyclodextrin compounds containing benzoic,acetylsalicylic, and 2-(4-isobutylphenyl)propionic acid residues

Selectively substituted derivatives of α-cyclodextrin and hexa-O-tert-butyldimethylsilyl-α-cyclodextrin containing a definite number of acylated primary or secondary hydroxy groups were synthesized using benzoic, acetylsalicylic, and 2-(4-isobutylphenyl)propionic acid chlorides in various solvents in the presence of different bases. The acyl residues were assigned to the C², C³, or C⁶ atoms in the carbohydrate fragments on the basis of ¹³C NMR data. Desilylation of the silyl derivatives with ammonium fluoride in methanol gave the corresponding O-acyl derivatives having free primary hydroxy groups in the α-cyclodextrin skeleton.     

Nitrogen bridgehead compounds. Part 85. Synthesis and reactivity of 3,4-dihydro-1H,6H[1,4]oxazino[3,4-b]quinazolin-6-ones

3,4-Dihydro-1H,6H-[1,4]oxazino[3,4-b]quinazolin-6-one 3 and its 1-methyl and 1-hydroxy derivatives 8 and 13 were prepared by different routes. The active methylene group of compound 3 was reacted with electro-hilic reagents (bromine, phenyldiazonium chloride, nitrous acid, a Vielsmeier-Haack reagent, aromatic aldehydes and diethyl oxalate) to yield 1-substituted-3,4-dihydro[1H,6H)-1,4-oxazino[3,4-b]quinazo-lin-6-ones. The reactivity of 1-hydroxy and 1-bromo derivatives 13 and 15 were also investigated in some reactions. The 3,4-dihydro-lH,6H-[1,4]oxazino[3,4-b]quinazolin-6-ones were characterized by means of uv, ¹H and ¹³C nmr spectroscopy.     

Synthesis and Reactions of Some New Benzo[a]phenothiazine‐3,4‐dione Derivatives

The reaction of 2,3‐dihydro‐2,3‐epoxy‐1,4‐naphthoquinone ( 4 ) with substituted anilines furnished the corresponding benzo[fused]heterocyclic derivatives 5 , 6 , 6a , 6b , 7 , 8 . Furthermore, treatment of benzo[a]phenothiazine derivative 7 with halo compounds, namely, ethyl bromoacetate, phenacyl bromide, dibromoethane, or chloroacetone afforded ether derivatives 11 , 12 , 13 , 14 , respectively. Moreover, the reaction of 11 with o‐substituted aniline gave the corresponding benzo[a]phenothiazin‐5‐one derivatives 15 , 16 , 17 and benzo[d][1,3]oxazin‐4‐one 18 , respectively. Finally, the chromenone derivative 19 was synthesized via the reaction of ester derivative 11 with salicyaldhyde in refluxing pyridine. The newly synthesized compounds were characterized by spectroscopic measurements (IR, ¹H NMR, ¹³C NMR, and mass spectra).     

Synthesis,Structural Characterization,and Biological Evaluation of Novel Substituted 1,3‐Thiazole Derivatives Containing Schiff Bases

In this study, thiazole derivatives containing Schiff bases ( 7a , 7b , 7c , 7d , 7e , 7f , 8a , 8b , 8c , 8d , 8e , 8f , 9a , 9b , 9c , 9d , 9e , 9f ) were synthesized in moderate to high yields (49–94%) using the Hantzsch reaction with thiosemicarbazone derivatives ( 5a , 5b , 5c ) and 2‐bromo‐1‐phenylethanone derivatives ( 6a , 6b , 6c , 6d , 6e , 6f ). The structures of synthesized compounds were elucidated by IR, ¹H NMR, ¹³C NMR, elemental analyses, mass spectroscopy and X‐ray diffraction analysis techniques. Moreover, the synthesized compounds were tested for their in vitro antifungal activity and most of them exhibited moderate to good activity against Fusariumoxysporumf.sp. lycopersici.      

119Sn NMR Spectra of Some Carbohydrate Organotin Derivatives

Abstract

The ¹¹⁹Sn NMR spectra of several sugar-tin derivatives were recorded. The geometric and steric isomers of all of the organotin derivatives studied were easily differentiated by ¹¹⁹Sn NMR. The appropriate ¹¹⁹Sn resonances are: ca - 50 ppm for trans and ?60 ppm for cis vinyltin derivatives (1-3), ca 16 ppm for allyltins 4-6, and ca ?32 ppm for tin-carbinols 9 and 11. When the hydroxyl group in carbinol 9 was converted to an O-acetyl group, the chemical shift of ¹¹⁹Sn was shifted to ?22 ppm.     

Nitrogen bridgehead compounds. Part 45 [1]. Synthesis of 6-arylhydrazono-6,7,8,9-tetrahydro-11H-pyrido-[2,1-b]quinazolin-11-ones

A series of 6-arylhydrazono-6,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolin-11-ones 3–37 , conveneint starting materials for indolopyridoquinazolines, were prepared by diazonium coupling between aryldiazonium chlorides and 6,7,8,9-tetrahydro- 2 , 6-formyl-5,7,8,9-tetrahydro- 39 , 6-(dimethylamino)methylene-6,7,8,9- 38 or 6-carboxyl-5,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolin-11-ones 43 . The arylhydrazono derivatives were also prepared from 6-bromo- 45 or 6,6-dibromo-6,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolines 46 with arylhydrazines. The structures of the 6-arylhydrazonopyridoquinazolines were characterized by uv and ¹H nmr spectroscopy. The 6-arylhydrazono derivatives show a solvent-dependent E-Z isomerism.     

Synthesis and Structural Characterisation of Two Novel Diastereoisomeric Naproxen Appended β-Cyclodextrin Derivatives

The condensation reaction of 6-deoxy-6-amino(2-aminoethyl)-cyclomaltoheptaose (β-CyDen) and racemic [(R, S)-2-(6-methoxy-2-naphthyl) propanoic acid] (R,S-naproxen) affords two new diastereoisomeric naproxen-appended β-cyclodextrin derivatives. The structural analysis of these two β-CyD derivatives, undertaken by combined use of circular dichroism (CD) and 1D or 2D NMR techniques, shows that the naphthalene ring of the naproxen is included in the CyD cavity in both derivatives. The CD spectra are consistent with an axial complexation model, moreover, the self-inclusion mode is further corroborated by ¹H NMR ROESY spectra which also suggest the orientation of the naphthyl moiety in the cavity of both the diastereoisomers.     

Synthesis and Spectroscopic Characterization of Some Hydrazone and 2H‐benzopyranone Derivatives as Antitumor Agents

A new series of hydrazone, 2H‐benzopyranone‐3‐carboxamide and 2H‐benzopyranone‐3‐carbonylthiosemicarbazide derivatives were synthesized from the alkyl 7‐hydroxy‐2H‐benzopyranone‐3‐carboxylate ( 1a , b ) and dibromo derivatives ( 6a , b ) as a key starting materials. The structures of the synthesized new compounds were confirmed by IR, ¹H, ¹³C‐NMR, MS, and elemental analysis. Some hydrazone derivatives and N‐substituted 2H‐benzopyranone‐3‐carboxamides were evaluated for their anticancer activity against HepG‐2 cell lines. Some of these compounds shared good cytotoxicity.     

Photochemical intramolecular nitrene insertion of 6-azidouridine derivatives

A highly efficient intramolecular nitrene insertion was observed upon irradiation of 6-azidouridine derivatives. The N⁶,2′-cyclo structure of the product was determined unequivocally by X-ray crystallography.