Preparation,molecular structures,and characteristic properties of (E)-1-(2-furyl)- and (E)-1-(2-thienyl)-2-(3-guaiazulenyl)ethylenes and (E)-1-(3-furyl)- and (E)-1-(3-thienyl)-2-(3-guaiazulenyl)ethylenes

Wittig reactions of 2-furaldehyde (20) [and thiophene-2-carbaldehyde (21)] with (3-guaiazulenylmethyl)triphenylphosphonium bromide (19) in ethanol containing NaOEt at 25 °C for 24 h under argon give (E)-1-(2-furyl)-2-(3-guaiazulenyl)ethylene (22E) and (E)-1-(2-thienyl)-2-(3-guaiazulenyl)ethylene (23E) in 53 and 36% yields. Similarly, Wittig reactions of 3-furaldehyde (29) [and thiophene-3-carbaldehyde (30)] with 19 under the same reaction conditions as for 20 and 21 afford (E)-1-(3-furyl)-2-(3-guaiazulenyl)ethylene (31E) and (E)-1-(3-thienyl)-2-(3-guaiazulenyl)ethylene (32E) in 32 and 46% yields. Molecular structures and characteristic properties as well as preparation of the title E (i.e., one of the geometrical isomers) forms, with a view to comparative study, are reported. Moreover, reactions of those conjugated π-electron systems with TCNE (=tetracyanoethylene) in benzene [and in DMF (=N,N-dimethylformamide)] at 25 °C for 24 h under argon yield unique products, possessing interesting molecular structures, respectively, whose characteristic properties and crystal structures are documented, also.     

Serendipitous stereoselective synthesis of brand-new fluorescent dyes: (1Z)-3-(alkylimino)-1-[(chromone-3-yl)methylene]-1,3-dihydro-9H-furo[3,4-b]chromen-9-one-type fluorophores with blue fluorescence emission properties

The reactions of 3-formylchromones with alkyl isocyanides in dry dichloromethane at room temperature lead to new types of organic fluorophores (1Z)-3-(alkylimino)-1-[(chromone-3-yl)methylene]-1,3-dihydro-9H-furo[3,4-b]chromen-9-one, which exhibited strong blue emission in solution. The reactions involve a [4+1] cycloaddition followed by an activated electrophilic aromatic substitution at the furan ring and dehydration sequence.     

Synthesis of new modified aza heterocycles on the basis of 5-(2-chloro-1-nitroalkyl)-3-phenyl-and 5-(2-chloro-1-nitroalkyl)-3-methyl-1,2,4-oxadiazoles

3-Phenyl-and 3-methyl-5-(2-chloro-1-nitroalkyl)-1,2,4-oxadiazoles reacted with piperidine, pyrrolidine, and morpholine to give the corresponding 5-(2-amino-1-nitroalkyl) derivatives, while their reactions with sodium p-toluenesulfinate led to the formation of 2-[3-methyl(or phenyl)-1,2,4-oxadiazol-5-yl]-2-nitroethyl p-tolyl sulfones.     

Synthesis of 5-substituted 2-(4- or 3-methoxyphenyl)-4(1H)-quinolones

5-Substituted 7-methoxy-2-(4- or 3-methoxyphenyl)-4(1H)-quinolones 8-17 have been synthesised in good yields from the corresponding 7-methoxy-2-(4- or 3-methoxyphenyl)-5-trifluoromethanesulfonate-4(1H)-quinolones 7 via palladium-mediated cross-coupling reactions or aromatic nucleophilic substitution (SN_Ar) reactions.     

Synthesis of diarylheptanoids, (5S)-5-acetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-3-heptanone and (3S,5S)-3,5-diacetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane

The total syntheses of the first examples of diarylheptanoid natural products (5S)-5-acetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-3-heptanone 1, and (3S,5S)-3,5-diacetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane 2 isolated from the rhizomes of Zingiber officinale were accomplished using Sharpless epoxidation and cross-metathesis reactions as the key steps.     

Chemoenzymatic synthesis of (3R,4S)- and (3S,4R)-3-methoxy-4-methylaminopyrrolidine

An efficient and a convenient enantioselective synthesis of (3R,4S)-3-methoxy-4-methylaminopyrrolidine has been carried out by a lipase-mediated resolution protocol. This method describes the preparation of (±)-1-Cbz-cis-3-azido-4-hydroxypyrrolidine starting from commercially available diallylamine followed by ring-closing metathesis (RCM) via S_N2 displacement reactions. Pseudomonas cepacia lipase immobilized on diatomaceous earth (Amano PS-D) provides (3R,4S)-11 and (3S,4R)-12 in an excellent enantiomeric excess.     

4-functionally substituted 3-hetarylpyrazoles: XX. Synthesis of derivatives of 5-(pyrasol-4-yl)-1,2,4-triazole and 3-(pyrazol-4-yl)-1,2,4-triazolo[3,4-c][1,4]oxazine

N-Methylimines of 3-aryl-1-phenylpyrazole-4-carbaldehyde react with ethyl 2-aryl-hydrazino-2-chloroacetate with the formation of ethyl 1-aryl-5-(pyrazole-4-yl)-4,5-dihydro-1H-1,2,4-triazolecarboxylates. Analogous reactions of pyrazol-4-carbaldehyde N-(2-hydroxy)ethylimines results in derivatives of 3-(pyrazol-4-yl)-1,2,4-triazolo[3,4-c][1,4]-oxazines.     

The Synthesis of 3-(R)- and 3-(S)-Hydroxyeicosapentaenoic Acid

Monohydroxylated polyunsaturated fatty acids belonging to the oxylipin class of natural products are present in marine and terrestrial sources as well as in the human body. Due to their biological activities and role in diverse biosynthetic pathways, oxylipins biosynthesized from eicosapentaenoic acid and arachidonic acid have attracted great interest from the scientific community. One example is 3-hydroxyeicosapentaenoic acid where the absolute configuration at C-3 has only been tentatively assigned. In this paper, studies on acetate type aldol reactions that enabled the preparation of 3-(R)-hydroxyeicosapentaenoic acid (3R-HETE, 2) and its enantiomer are presented.     

Chemoenzymatic synthesis of (3S,4S)- and (3R,4R)-3-methoxy-4-methylaminopyrrolidine

Facile chemoenzymatic enantioselective synthesis of (3S,4S)-3-methoxy-4-methylaminopyrrolidine, a key intermediate for a new quinolone antitumor compound AG-7352 has been described. This methodology illustrates the preparation of 3-azido-1-benzyloxycarbonyl-4-hydroxypyrrolidine starting from diallylamine via 1-benzyloxycarbonyl-3-pyrroline obtained by ring-closing metathesis (RCM) employing Grubbs’ catalyst. Enzymatic transesterification employing PS-C lipase gave (3S,4S)-3-azido-1-benzyloxycarbonyl-4-hydroxypyrrolidine in >99% ee, which upon methylation of the hydroxyl group followed by sequential reactions gave the desired intermediates, (3S,4S)-1-tert-butoxycarbonyl-3-tert-butoxycarbonylamino-4-methoxypyrrolidine.     

A concise enantioselective synthesis of (+)-goniodiol and (+)-8-methoxygoniodiol via Co-catalyzed HKR of anti-(2SR, 3RS)-3-methoxy-3-phenyl-1, 2-epoxypropane

A short, enantioselective synthesis of (+)-goniodiol and (+)-8-methoxygoniodiol, cytotoxic styryllactones, has been achieved in high optical purities (99% ee). The strategy employs Co-catalyzed HKR of racemic anti-(2SR, 3RS)-3-methoxy-3-phenyl-1, 2-epoxypropane and Lewis acid-mediated diastereoselective allylation of aldehyde as chiral inducing key reactions.     

Reductions of (1R,3R,4R)-3-([1,2,4]triazolo[4,3-x]azin-3-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones and their analogues

Reductions of (1R,3R,4R)-3-([1,2,4]triazolo[4,3-x]azin-3-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones and their lactone analogues, prepared from (1R)-(+)-camphor, were studied. Catalytic hydrogenation selectively led to partial saturation of the [1,2,4]triazolo[4,3-x]azine residue, while in reactions with borane–methylsulfide coordination of borane to the 1-position of [1,2,4]triazolo[4,3-x]azine system took place. On the other hand, activation of the carbonyl group in (1R,3R,4R)-3-([1,2,4]triazolo[4,3-x]azin-3-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones with boron trifluoride etherate followed by reaction with borane–methylsulfide furnished the corresponding isoborneols, stereoselectively. The structures of all representative compounds were confirmed by X-ray diffraction.     

Microwave-assisted synthesis of the Schöllkopf chiral auxiliaries: (3S)- and (3R)-3,6-dihydro-2,5-diethoxy-3-isopropyl-pyrazine

A practical and efficient methodology for the laboratory scale preparation of Schöllkopf’s bis-lactim ether chiral auxiliaries (3S)- and (3R)-3,6-dihydro-2,5-diethoxy-3-isopropyl-pyrazine has been developed. The key step is the preparation of the 2,5-diketopiperazine derivative by microwave-assisted heating in water. The protocol avoids reactions at low temperature and the use of high boiling solvents. Only inexpensive and readily available starting materials are required. The bis-lactim ethers were produced in high yields on a multigram scale.     

Synthesis and some transformations of 2-(2-thienyl)-1(3)H-imidazo[4,5-f] quinoline

2-(2-Thienyl)-1(3)H-imidazo{cm[4,5-f]}quinoline was synthesized by the Weidenhagen reaction of quinoline-5,6-diamine with thiophene-2-carbaldehyde. Its methylation in the system KOH-DMSO gave isomeric 1-methyl-2-(2-thienyl)-1H- and 3-methyl-2-(2-thienyl)-3H-imidazo{cm[4,5-f]}quinolines, the latter being the major product. The 3-methyl derivative was subjected to electrophilic substitution reactions (bromination, nitration, formylation, acylation, sulfonation). Depending on the conditions, electrophilic attack was directed at the thiophene or quinoline fragment or both these.     

Assymetric synthesis of (2S,3R)- and (2S,3S)-[2-C;3-H] glutamic acid

We have developed a synthetic route for (2S,3R)- and (2S,3S)-[2-¹³C;3-²H] glutamic acids with high enantioselectivity. The key reactions in this synthesis are the asymmetric reduction of the 2,3-didehydroornithine derivative using the (S,S)-Et-DuPHOS-Rh catalyst and the oxidation of the δ-position by ruthenium catalysis.     

Aminomethylation of 6-methyl-1-(thietan-3-yl)pyrimidine-2,4(1H,3H)-dione

Mannich reactions of 6-methyl-1-(thietan-3-yl)pyrimidine-2,4(1H,3H)-dione with formaldehyde and morpholine, piperidine, N-methylpiperazine, and diethylamine gave the corresponding 5-aminomethylsubstituted pyrimidine derivatives. The title compound reacted with excess piperazine to form 3,5-bis-(piperazin-1-yl) derivative, while its reaction with an equimolar amount of piperazine afforded 5,5′-(piperazin-1,4-diylbismethylene)bis[6-methyl-1-(thietan-3-yl)pyrimidine-2,4(1H,3H)-dione].     

2-(2-Furyl)-1(3)H-imidazo[4,5-f]quinoline. Synthesis and electrophilic substitution reactions

2-(2-Furyl)-1(3)H-imidazo[4,5-f]quinoline was synthesized by the Weidenhagen reaction of quinoline-5,6-diamine with furfural. Its alkylation with methyl iodide in the system KOH-DMSO gave two isomeric N-methyl derivatives, 2-(2-furyl)-1-methyl-1H- and 2-(2-furyl)-3-methyl-3H-imidazo[4,5-f]quinolines, the latter prevailing. 2-(2-Furyl)-3-methyl-3H-imidazo[4,5-f]quinoline was brought into electrophilic substitution reactions: bromination, nitration, formylation, acylation, sulfonation. Depending on the reaction conditions, electrophilic attack could be directed at both furan ring and quinoline fragment.     

Tele-substitution reactions in the naphthalene series : The behaviour of 1,4 - dimethyl - 2 - nitro - 3 - phenylsulphonyl - and 2,3 - bisphenylsulphonyl - 1,4 - dimethyl - naphthalene towards sodium arenethiolates and secondary aliphatic amines

1,4 - Dimethyl - 2 - nitro - 3 - phenylsulphonylnaphthalene (2) reacts with sodium benzenethiolate in DMSO at 120° to give 1 - methyl - 2 - nitro - 4 - phenylthiomethylnaphthalene (4) [tele-substitution product (TSP) of the phenylsulphonyl group] and 1,4 - dimethyl - 3 - phenylsulphonyl - 2 - phenylthionaphthalene (5) [normal substitution product (NSP) of the nitro group]. The analogous reactions of 2 with sodium 2,4,6- trimethylbenzenethiolate and of 2,3 - bisphenylsulphonyl -1,4 - dimethylnaphthalene (3) with sodium benzenethiolate or aliphatic amines give only TSPs of the phenylsulphonyl group. In the case of the reaction of 2 with aliphatic amines both the possible TSPs (tele-substitution of the phenylsulphonyl or of the nitro group) were isolated in 9:1 relative yield. All the data show that the phenylsulphonyl is a leaving group far better than the nitro in such tele-substitution processes. The mechanism previously proposed to account for the formation of TSPs from 1,4-dimethyl - 2,3 - dinitronaphthalene is strongly supported by the obtained results.     

Transformations of (1E,3E)-1-(benzoylamino)-4-(dimethylamino)buta-1,3-diene-1,2,3-tricarboxylates into pyridine and pyrrole derivatives

New, highly functionalised (1E,3E)-1-(benzoylamino)-4-(dimethylamino)buta-1,3-diene-1,2,3-tricarboxylates proved to be useful and versatile reagents in the formation of highly substituted pyridine, N-aminopyridine, pyrrole and pyrido[3,4-c]pyridazine derivatives. The formation of the particular type heterocyclic system is dependent on the starting (1E,3E)-1-(benzoylamino)-4-(dimethylamino)buta-1,3-diene-1,2,3-tricarboxylate. By an appropriate choice of different ester groups it is possible to drive the reactions towards the formation of either pyridine or pyrrole derivatives.     

An efficient synthesis of (−)-3-deazaaristeromycin

The coupling reaction of 4-chloro-1H-imidazo[4,5-c]pyridine (6-chloro-3-deazapurine) and (3aS,4S,6R,6aR)-tetrahydro-2,2-dimethyl-6-vinyl-3aH-cyclopenta-[d][1,3]dioxo-4-ol under Mitsunobu reaction conditions provides, after three subsequent straightforward reactions, ready access to the highly biologically active (−)-3-deazaaristeromycin. The versatility of this procedure opens access to a diverse pool of 3-deazapurine carbocyclic nucleosides.     

Reactivity difference between diphosgene and phosgene in reaction with (2,3-anti)-3-amino-1,2-diols

In reactions of (2,3-anti)-3-amino-1,2-diols with diphosgene and phosgene and their conversion into 1,3-oxazolidin-2-ones, some differences in the stereochemistry of the reactions have been found with these two reagents. The reactions with phosgene afforded the expected cis-oxazolidinones, and in the reaction with diphosgene under the same reaction conditions, the trans-oxazolidinones were also obtained.