Efficient Synthesis of Novel Coumarin‐3‐carboxamides (=2‐Oxo‐2H‐1‐benzopyran‐3‐carboxamides) Containing Lipophilic Spacers

The novel coumarin‐3‐carboxamides (=2‐oxo‐2H‐1‐benzopyran‐3‐carboxamides) 5a – 5g containing lipophilic spacers were synthesized through the Ugi‐four‐component reaction (Scheme 1). The reactions of aromatic aldehydes 1 , 4,4′‐oxybis[benzenamine] or 4,4′‐methylenebis[benzenamine] as diamine 2 , coumarin‐3‐carboxylic acid (=2‐oxo‐2H‐benzopyran‐3‐carboxylic acid; 3 ), and alkyl isocyanides 4 lead to the desired substituted coumarin‐3‐carboxamides 5a – 5g at room temperature with high bond‐forming efficiency. These novel coumarin derivatives exhibit brilliant fluorescence at 544 nm in CHCl₃.     

Regioselective 1,3‐Dipolar Cycloadditions of (1Z)‐1‐(Arylmethylidene)‐5,5‐dimethyl‐3‐oxopyrazolidin‐1‐ium‐2‐ide Azomethine Imines to Acetylenic Dipolarophiles

The 5,5‐dimethylpyrazolidin‐3‐one ( 4 ), prepared from ethyl 3‐methylbut‐2‐enoate ( 3 ) and hydrazine hydrate, was treated with various substituted benzaldehydes 5a – i to give the corresponding (1Z)‐1‐(arylmethylidene)‐5,5‐dimethyl‐3‐oxopyrazolidin‐1‐ium‐2‐ide azomethine imines 6a – i . The 1,3‐dipolar cycloaddition reactions of azomethine imines 6a – h with dimethyl acetylenedicarboxylate (=dimethyl but‐2‐ynedioate; 7 ) afforded the corresponding dimethyl pyrazolo[1,2‐a]pyrazoledicarboxylates 8a – h , while by cycloaddition of 6 with methyl propiolate (=methyl prop‐2‐ynoate; 9 ), regioisomeric methyl pyrazolo[1,2‐a]pyrazolemonocarboxylates 10 and 11 were obtained. The regioselectivity of cycloadditions of azomethine imines 6a – i with methyl propiolate ( 9 ) was influenced by the substituents on the aryl residue. Thus, azomethine imines 6a – e derived from benzaldehydes 5a – e with a single substituent or without a substituent at the ortho‐positions in the aryl residue, led to mixtures of regioisomers 10a – e and 11a – e . Azomethine imines 6f – i derived from 2,6‐disubstituted benzaldehydes 5f – i gave single regioisomers 10f – i .     

Pericyclic Transformations at the Periphery of Chromen‐4‐one (=4H‐1‐Benzopyran‐4‐one): An Unusual Preference for a 1,5‐Shift of Allylic Moieties over the Ene Reaction

Quite unlike the reported facile ene reactions on the periphery of many related heterocyclic systems, similarly disposed moieties on the periphery of the chromen‐4‐one (=4H‐1‐benzopyran‐4‐one) system fail to undergo an ene reaction and display a rather unusual preference for an overall [1,5] shift of the allylic C‐atom. Thus, heating xylene solutions of 2‐(N‐allylanilino)‐, 2‐(N‐crotylanilino)‐, and 2‐(N‐cinnamylamino)‐substituted (E)‐(oxochromenyl)propenoates 9a – c and 2‐[allyl(benzyl)amino]‐, 2‐[benzyl(crotyl)amino]‐, and 2‐[benzyl(cinnamyl)amino]‐substituted (E)‐(oxochromenyl)propenoates 16a – c in a sealed tube at 220–230° leads to a [1,5] shift of the allylic moieties (allyl, crotyl, cinnamyl), which is followed by intramolecular cyclization involving the N‐atom and the ester function, to give the 3‐allyl‐3‐crotyl‐, and 3‐cinnamyl‐substituted‐1‐phenyl‐ or 1‐benzyl‐2H‐[1]benzopyrano[2,3‐b]pyridine‐2,5(1H)‐diones 10a – c and 17a – c . The anticipated carbonyl–ene reaction in the 2‐(N‐allylanilino)‐, 2‐(N‐crotylanilino)‐, 2‐(N‐cinnamylanilino)‐, 2‐[allyl(benzyl)amino]‐, 2‐[benzyl(crotyl)amino]‐, and 2‐[benzyl(cinnamyl)amino]‐substituted 4‐oxochromene‐3‐carboxaldehydes 8a – c and 15a – c is also not observed, and these molecules remain untransformed under identical conditions. No [1,5] shifts of benzyl, phenyl, or methyl groups are observed, even in the absence of allylic moieties, though facile [1,5]‐H shift occurs in 2‐(benzylamino)‐ and 2‐(phenylamino)‐substituted (E)‐(oxochromenyl)propenoates 23a , b , which is followed by a similar intramolecular cyclization leading to the 2H‐[1]benzopyrano[2,3‐b]pyridine‐2,5(1H)‐diones 24a , b .     

2,5‐Disubstituted Pyrazolo[4,3‐c]cinnolin‐3‐ones

Complementary strategies to 2,5‐disubstituted pyrazolo[4,3‐c ]cinnolin‐3‐ones are reported herein, providing late stage substituent introduction at either the 2‐ or the 5‐position. Treating a readily prepared 4‐thiocinnoline ester with substituted hydrazines afforded late stage access to the 2‐position, while late stage substituent introduction at the 5‐position was achieved via two different strategies: alkylation of 4‐hydrazonopyrazol‐3‐ones, followed by a ring‐closing intramolecular S_NAr tactic and direct reaction of 5‐(2‐fluorophenyl)‐2,4‐dihydro‐3H‐pyrazol‐3‐ones with aryl diazonium salts, followed by cyclization. The strategies described herein provide practical and general methods to prepare 2,5‐disubstituted pyrazolo[4,3‐c ]cinnolin‐3‐ones.     

A convenient synthesis of novel pyrido(1′,2′:1,2)imidazo[5,4‐d]‐1,2,3‐triazinones from imidazo[1,2‐a]pyridines

The imidazo[1,2‐a]pyridine system was investigated as a synthon for the building of very attractive fused triazines, a planar, angular tri‐heterocycle with potential biological activity. Thus ethyl 3‐nitroimidazo[1,2‐a]pyridine‐2‐carboxylate was treated with ammonia or with an excess of primary amines to generate the corresponding substituted nitro carboxamidoimidazopyridines. The nitro substituent in the latter products, was reduced to yield 3‐amino‐2‐carboxamidoimidazo[1,2‐a]pyridine derivatives, which in turn were treated with nitrous acid to furnish 1‐oxo‐2‐substituted pyrido(1′,2′:1,2)imidazo[5,4‐d]‐1,2,3‐triazines.     

Annosqualine: a Novel Alkaloid from the Stems of Annona squamosa

Annosqualine (=(10′bR)‐1′,5′,6′,10′b‐tetrahydro‐9′‐hydroxy‐7′,8′‐dimethoxyspiro[cyclohexa‐2,5‐diene‐1,2′‐pyrrolo[2,1‐a]isoquinoline]‐3′,4‐dione; 1 ), a novel alkaloid with an unprecedented skeleton, and a new amide, dihydrosinapoyltyramine (=3‐(4‐hydroxy‐3,5‐dimethoxyphenyl)‐N‐[2‐(4‐hydroxyphenyl)ethyl]propanamide; 2 ), were isolated from the stems of Annona squamosa L., together with six known alkaloids. The structures of all compounds were elucidated spectroscopically by means of optical rotation, ¹H‐, ¹³C‐, and 2D‐NMR, and by EI‐MS, or by comparison with the spectral data of authentic samples. A possible biogenetical pathway towards annosqualine ( 1 ) is proposed.     

Microwave‐Assisted Synthesis of Novel 2,4‐Dihydro‐5‐[4‐(trifluoromethyl)phenyl]‐3H‐1,2,4‐triazol‐3‐ones and Potentiometric Determination of Their pKa in Nonaqueous Solvents

The novel 4‐amino‐ or 4‐aryl‐substituted 2,4‐dihydro‐5‐[(4‐trifluoromethyl)phenyl]‐3H‐1,2,4‐triazol‐3‐ones 3a – 3g were synthesized by reaction of N‐(ethoxycarbonyl)‐4‐(trifluoromethyl)benzenehydrazonic acid ethyl ester ( 2 ) and primary amines or hydrazine by microwave irradiation. Compounds 3a – 3g were potentiometrically titrated with tetrabutylammonium hydroxide (Bu₄NOH) in four nonaqueous solvents, i.e., ⁱPrOH, ^tBuOH, MeCN, and N,N‐dimethylformamide (DMF). Also half‐neutralization potential values and the corresponding pK_a values were determined in all cases.     

Synthesis of Substituted Pyrrolo[3,4‐a]carbazoles

The cycloaddition between N‐protected 3‐{1‐[(trimethylsilyl)oxy]ethenyl}‐1H‐indoles and substituted maleimides (= 1H‐pyrrole‐2,5‐diones) yielded substituted pyrrolo[3,4‐a]carbazole derivatives bearing an additional succinimide (= pyrrolidine‐2,5‐dione) moiety either at C(5a) or C(10b) depending on the type of the protection group at the indole N‐atom. Derivatives substituted at C(10b) were isolated when the protection group, Me₃Si or Boc (^tBuOCO), was eliminated during the reaction (Schemes 2 and 3), whereas a substitution at C(5a) was observed when an electron‐withdrawing group, Tos (4‐MeC₆H₄SO₂) or pivaloyl (Me₃CCO), was not eliminated (Scheme 1). Complex results were found in reactions between 1‐(trimethylsilyl)‐3‐{1‐[(trimethylsilyl)oxy]ethenyl}‐1H‐indole, in contrast to formerly reported results (Scheme 3). Some derivatives of 1H,5H‐[1,2,4]triazolo[1′,2 : 1,2]pyridazino[3,4‐b]indole‐1,3(2H)‐dione were obtained from reactions with 4‐phenyl‐3H‐1,2,4‐triazole‐3,5(4H)‐dione (Scheme 2). All structures were established by spectroscopic data, by calculations, and one representative structure was confirmed by an X‐ray crystallographic analysis (Fig.). Finally, the formation of the different structure types was discussed, and compared with similar reactions reported in the literature.     

Synthesis of Derivatives of Pyrido[4,3‐d]pyrimidin‐4(3H)‐one via an Iminophosphorane

A series of new, 2‐substituted 3‐aryl‐8,9,10,11‐tetrahydro‐5‐methyl[1]benzothieno[3′,2′ : 5,6]pyrido[4,3‐d]pyrimidin‐4(3H)‐ones, compounds 5a – q , were designed and synthesized via the aza‐Wittig reaction as the key step. The iminophosphorane 1 reacted with phenyl isocyanate (or 4‐chlorophenyl isocyanate) to the carbodiimide 4 , which was cyclized to 5 upon addition of different amines, EtOH, or phenols in the presence of a catalytic amount of EtONa or K₂CO₃ (Schemes 1 and 2). The structures of compounds 5 were confirmed by IR, ¹H‐ and ¹³C‐NMR, EI‐MS, elemental analyses, and, in the case of 5l , by single‐crystal X‐ray diffraction (Figure).     

Photochemical Reactions of N‐(2‐Halogenoalkanoyl) Derivatives of Anilines

The photochemical reactions of 2‐substituted N‐(2‐halogenoalkanoyl) derivatives 1 of anilines and 5 of cyclic amines are described. Under irradiation, 2‐bromo‐2‐methylpropananilides 1a – e undergo exclusively dehydrobromination to give N‐aryl‐2‐methylprop‐2‐enamides (=methacrylanilides) 3a – e (Scheme 1 and Table 1). On irradiation of N‐alkyl‐ and N‐phenyl‐substituted 2‐bromo‐2‐methylpropananilides 1f – m , cyclization products, i.e. 1,3‐dihydro‐2H‐indol‐2‐ones (=oxindoles) 2f – m and 3,4‐dihydroquinolin‐2(1H)‐ones (=dihydrocarbostyrils) 4f – m , are obtained, besides 3f – m . On the other hand, irradiation of N‐methyl‐substituted 2‐chloro‐2‐phenylacetanilides 1o – q and 2‐chloroacetanilide 1r gives oxindoles 2o – r as the sole product, but in low yields (Scheme 3 and Table 2). The photocyclization of the corresponding N‐phenyl derivatives 1s – v to oxindoles 2s – v proceeds smoothly. A plausible mechanism for the formation of the photoproducts is proposed (Scheme 4). Irradiation of N‐(2‐halogenoalkanoyl) derivatives of cyclic amines 5a – c yields the cyclization products, i.e. five‐membered lactams 6a , b , and/or dehydrohalogenation products 7a , c and their cyclization products 8a , c , depending on the ring size of the amines (Scheme 5 and Table 3).     

Synthesis and Reactions of the Novel 6‐ethyl‐4‐hydroxy‐2,5‐dioxo‐5,6‐dihydro‐2H‐pyrano[3,2‐c]quinoline‐3‐carboxaldehyde

The novel 6‐ethyl‐4‐hydroxy‐2,5‐dioxo‐5,6‐dihydro‐2H‐pyrano[3,2‐c]quinoline‐3‐carboxaldehyde ( 2 ) was efficiently synthesized from Vilsmeier–Haack formylation of 3‐(1‐ethy1‐4‐hydroxy‐2‐oxo‐(1H)‐quinolin‐3‐yl)‐3‐oxopropanoic acid ( 1 ). The aldehyde 2 was allowed to react with some nitrogen nucleophiles producing a variety of hydrazones 3 – 7 . Reaction of aldehyde 2 with hydrazine hydrate and hydroxylamine hydrochloride afforded pyrazole and isoxazole annulated pyrano[3,2‐c]quinoline‐2,5(6H)‐dione, respectively. The reactivity of aldehyde 2 was examined toward some active methylene nitrile, namely, malononitrile, ethyl cyanoacetate, and cyanoacetamide leading to 2‐iminopyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines 10 – 12 , respectively. Also, some novel pyrazolo[4″,3″:5′,6′]pyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines ( 13 , 14 ) and thiazolo[5″,4″:5′,6′]pyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines ( 15 , 16 ) were synthesized. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data.     

Selbstorganisation von Chinodimethanen über kovalente Bindungen,Mitteilung III,Untersuchungen zur Herstellung von Nanostrukturen

Self‐Assembly of Quinodimethanes through Covalent Bonds. Part III. Investigations on the Preparation of Nanostructures As part of our studies on the tetramerization of quinodimethane 1 to the macrocyclic compound 2 , the influence of substituents on this reaction was investigated. It was found that a large range of substituents such as 2‐phenylethyl, 2‐(4‐methoxyphenyl)ethyl, 2‐(4‐fluorophenyl)ethyl, 2‐[4‐(tert‐butyl)phenyl]ethyl, and 2‐[4‐(2‐phenylethyl)phenyl]ethyl, attached at positions 2 and 7 of 9H‐fluorene, do not prevent the tetramerization. The key step in the formation of the macrocylic compounds 13a – e is the debromination of 12a – e with mercury to the corresponding quinodimethanes which undergo a self‐assembly forming 13a – e in high yields. To study the conjugative influence of substituents on tetramerization, the effect of the hex‐1‐ynyl groups at positions 3 and 6 of the 9H‐fluorene rings was investigated. In this case, the corresponding macrocycle 17 was generated by the reaction of diol 16a with SnCl₂. Although the expected tetramerization to 17 occurred, the yield was lower than in the case of 13a – e , due to the sensitivity of the product.     

An Efficient Synthesis of Novel Benzo‐Fused Macrocyclic Dilactams

A facile synthetic approach was adopted towards the synthesis of benzo‐fused macrocyclic lactams 2a – 2g via the base‐catalyzed condensation reaction of 2,2′‐[alkanediylbis(oxy)]bis[benzaldehydes] 3a – 3c with N,N′‐substituted bis[2‐cyanoacetamide] derivatives 7a – 7c (Scheme 2). The latter compounds were obtained by the reaction of the appropriate diamines 6a – 6c with ethyl 2‐cyanoacetate ( 4 ). Attempts to prepare the oxaaza macrocycles 2 by alternative pathways were also investigated. The novel pyrazolo‐fused macrocycles 13a and 13b were obtained in 48 and 52% yield, respectively, upon treatment of 2d and 2g with NH₂NH₂?H₂O at 100° (Scheme 4).     

Ring Opening and Recyclization Reactions with Chromone‐3‐carbonitrile

Chemical transformations of chromone‐3‐carbonitrile ( 1 ) with some substituted hydrazines, namely, thiosemicarbazide, S‐methyl/benzyldithiocarbazate, 7‐chloro‐4‐hydrazinoquinoline, and 3‐hydrazino‐5,6‐diphenyl‐1,2,4‐triazine, led to substituted pyrazoles 2 , 5 – 8 . Ring opening of carbonitrile 1 followed by recyclization with 3‐amino‐1,2,4‐triazole and 2‐aminobenzimidazole gave triazolo[1,5‐a]pyrimidine 9 and pyrimido[1,2‐a]benzimidazole 10 , respectively. Treatment of carbonitrile 1 with some heterocyclic amines produced 2‐amino‐3‐substituted‐chromones 11 and 12 . The novel 3‐hydroxychromeno[4,3‐b]pyrazolo[4,3‐e]pyridin‐5(1H)‐one ( 13 ) was efficiently synthesized from the ring conversion of carbonitrile 1 with cyanoacetohydrazide. A mixture of chromeno[2,3‐b]naphthyridine 14 and chromeno[4,3‐b]pyridine 15 was obtained from base catalyzed transformation of carbonitrile 1 with malononitrile dimer. A diversity of novel annulated chromeno[2,3‐b]pyridines 16 – 22 was also synthesized. Chromeno[2,3‐b]pyrrole‐2‐carboxylate 23 was obtained from the reaction of carbonitrile 1 with ethyl chloroacetate. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data.     

4‐(2‐Hydroxyphenyl)‐2‐phenyl‐2,3‐dihydro‐1H‐1,5‐benzodiazepine and the 2‐(2,3‐dimethoxyphenyl)‐, 2‐(3,4‐dimethoxyphenyl)‐ and 2‐(2,5‐dimethoxyphenyl)‐substituted derivatives

The 1,5‐benzodiazepine ring system exhibits a puckered boat‐like conformation for all four title compounds [4‐(2‐hydroxyphenyl)‐2‐phenyl‐2,3‐dihydro‐1H‐1,5‐benzodiazepine, C₂₁H₁₈N₂O, (I), 2‐(2,3‐dimethoxyphenyl)‐4‐(2‐hydroxyphenyl)‐2,3‐dihydro‐1H‐1,5‐benzodiazepine, C₂₃H₂₂N₂O₃, (II), 2‐(3,4‐dimethoxyphenyl)‐4‐(2‐hydroxyphenyl)‐2,3‐dihydro‐1H‐1,5‐benzodiazepine, C₂₃H₂₂N₂O₃, (III), and 2‐(2,5‐dimethoxyphenyl)‐4‐(2‐hydroxyphenyl)‐2,3‐dihydro‐1H‐1,5‐benzodiazepine, C₂₃H₂₂N₂O₃, (IV)]. The stereochemical correlation of the two C₆ aromatic groups with respect to the benzodiazepine ring system is pseudo‐equatorial–equatorial for compounds (I) (the phenyl group), (II) (the 2,3‐dimethoxyphenyl group) and (III) (the 3,4‐dimethoxyphenyl group), while for (IV) (the 2,5‐dimethoxyphenyl group) the system is pseudo‐axial–equatorial. An intramolecular hydrogen bond between the hydroxyl OH group and a benzodiazepine N atom is present for all four compounds and defines a six‐membered ring, whose geometry is constant across the series. Although the molecular structures are similar, the supramolecular packing is different; compounds (I) and (IV) form chains, while (II) forms dimeric units and (III) displays a layered structure. The packing seems to depend on at least two factors: (i) the nature of the atoms defining the hydrogen bond and (ii) the number of intermolecular interactions of the types O—H...O, N—H...O, N—H...π(arene) or C—H...π(arene).     

Labelling of Carbaboranyl Compounds with a Selenium Atom with a View to Applications in Boron‐Neutron‐Capture Therapy (BNCT) and Positron‐Emission Tomography (PET)

We synthesized 2′‐carbaboranyl‐2,5′‐bi‐1H‐benzimidazoles containing 10 B‐atoms and labeled with Se or the positron‐emitting radionuclide ⁷³Se (t_1/2=7.1 h), with a view to their application to cancer treatment by boron‐neutron‐capture therapy (BNCT) and to compound‐distribution measurements in vivo by positron‐emission tomography (PET). Thus, 2,2′‐{{2′‐{4‐[1,2‐dicarba‐closo‐dodecaboran(12)‐2‐ylmethoxy]phenyl}‐[2,5′‐bi‐1H‐benzimidazol]‐5‐yl}imino}bis[ethanol] ( 26c ) was obtained by the reaction of 2,2′‐[(3,4‐diaminophenyl)imino]bis[ethanol] ( 19 ) with ethyl 2‐{4‐[1,2‐dicarba‐closo‐dodecaboran(12)‐2‐ylmethoxy]phenyl}‐1H‐benzimidazole‐5‐carboximidate hydrochloride ( 25 ), as well as the analogues 26a and 26b (Scheme 6). Tosylation of compound 26c gave 4 regioisomers 27a – d , which, after selenation, produced 2′‐{4‐[1,2‐dicarba‐closo‐dodecaboran(12)‐2‐ylmethoxy]phenyl}‐5‐(tetrahydro‐2H‐1,4‐selenazin‐4‐yl)‐2,5′‐bi‐1H‐benzimidazole ( 29 ) in 42% yield (Scheme 7).     

Highly Efficient [3 + 2] Cycloaddition: Click Synthesis of Novel 1H‐indol‐3‐yl‐benzo[d]imidazole Bis‐triazoles

A series of novel 1‐((1H‐1,2,3‐triazol‐4‐yl)methyl)‐2‐(1‐((1H‐1,2,3‐triazol‐4‐yl)methyl)‐5‐substituted‐1H‐indol‐3‐yl)‐6‐substituted‐1H‐benzo[d]imidazoles 5a – i have been prepared using click chemistry as an ideal strategy where [3 + 2] cycloaddition of azides with terminal alkynes has been developed as the target compounds. In route‐II, 5‐substituted‐1H‐indole‐3‐carbaldehydes 1a – c react with 5‐substituted orthophenylenediamine 8 to give desired products, that is, 6‐substituted‐2‐(5‐substituted‐1H‐indol‐3‐yl)‐1H‐benzo[d]imidazole 6a – i . Here, 6a – i react with 2 equiv of propargylbromide 7 to give novel 6‐substituted 2‐(5‐substituted‐1‐(prop‐2‐yn‐1‐yl)‐1H‐indol‐3‐yl)‐1‐(prop‐2‐yn‐1‐yl)‐1H‐benzo[d]imidazole 4a – i . 4a – i were reacted with 2 equiv of NaN₃ in t‐butanol/water (1:2) and add catalytic amount of CuSO₄.5H₂O. Stir the reaction mixture at room temperature to get the target products 5a – i . Here, obtained products contain four rings, that is, one indole, two triazoles, and one benzimidazole. The main advantages of this method are short reaction times, easy workup, higher yields (88–92%), and no by‐products formation.     

Identification of Three New Flavonoids from the Peels of Citrus unshiu

Three new flavonoids, 5,6,7,8,3′,4′‐hexamethoxyhomoflavone ( 1 ), 5,6,7,8,4′‐pentamethoxyhomoflavone ( 2 ) and 3,6,7,8,2′,5′‐hexamethoxyflavone ( 3 ) were isolated from the peels of mature fruits of Citrus unshiu Marcow (Rutaceae), together with the three known compounds 6,7,8,4′‐tetramethoxyflavone (=6,7,8‐trimethoxy‐2‐(4‐methoxyphenyl)‐4H‐1‐benzopyran‐4‐one), 3,5,7,8,2′,5′‐hexamethoxyflavone (=2‐(2,5‐dimethoxyphenyl)‐3,5,7,8‐tetramethoxy‐4H‐1‐benzopyran‐4‐one), and scopoletin (=7‐hydroxy‐6‐methoxy‐2H‐1‐benzopyran‐2‐one) of which the former two have never been isolated from natural resources, although they have been reported as synthetic compounds. The structures of 1 – 3 were elucidated on the basis of spectroscopic evidence, including 1D‐ and 2D‐NMR analysis.     

Nucleotides. Part LXXVI

A series of new fluorescing 8‐(6‐hydroxyhexyl)isoalloxazine (=8‐(6‐hydroxyhexyl)benzo[g]pteridine‐2,4(1H,3H)‐dione) derivatives 4 – 13 were synthesized from 6‐[(6‐hydroxyhexyl)amino]uracil ( 2 ) with 1‐chloro‐4‐nitrosobenzene via 8‐chloro‐10‐(6‐hydroxyhexyl)isoalloxazine ( 3 ) and subsequent substitution of the Cl‐atom of 3 by various amines (Scheme). Analogously, 8‐substituted 10‐{3‐[(2,2‐dimethyl‐1,3‐dioxolan‐4‐yl)methoxy]propyl}isoalloxazines 19, 20 , and 23 – 25 were prepared which yielded on deprotection the corresponding 10‐[3‐(2,3‐dihydroxypropoxy)propyl]alloxazines 21, 22 , and 26 – 28 . Their conversion into the 3″‐O‐(4,4′‐dimethoxytrityl) derivatives 29 – 33 and subsequent transformation into the corresponding 2″‐(2‐cyanoethyl N,N‐diisopropylphosphoramidites) 34 – 38 led to new building blocks for oligonucleotide synthesis. A series of 21‐mer oligodeoxyribonucleotides carrying the fluorescing isoalloxazine 37 in various positions of the chain were assembled in a DNA synthesizer. Combination with the complementary sequence yielded the stable duplexes 40 – 54 showing by the melting temperatures T_m that the fluorophor ( F ) does not harm the stability of the unmodified duplex 39 (Table).