Asymmetric synthesis of 5-(1-hydroxyalkyl)-5-methyl-5H-furan-2-ones

The reactivity of 5-methyl-4-(pyrrolidin-1-yl)-5H-furan-2-one with aldehydes and with acyl chlorides followed by reduction was studied. The aldol condensation gave predominantly the anti aldol product when the acylation-reduction sequence led exclusively to the syn product. The use of a chiral pyrrolidine, (S)-2-methoxymethylpyrrolidine (SMP), allowed the synthesis of enantio-enriched compounds, the acylation-reduction leading to the (R,R) addition product.     

Synthesis of 5-substituted 3-[5-(2,5-dimethylphenyl)-1,2-oxazol-3-yl]-1,2,4-oxadiazoles

5-(2,5-Dimethylphenyl)-1,2-oxazole-3-carbaldehyde oxime reacted with acetic anhydride in pyridine to give 5-(2,5-dimethylphenyl)-1,2-oxazole-3-carbonitrile which was converted into the corresponding amide oxime by treatment with hydroxylamine. O-Acyl derivatives of N′-hydroxy-5-(2,5-dimethylphenyl)-1,2-oxazole-3-carboximidamide underwent heterocyclization into 5-substituted 3-[5-(2,5-dimethylphenyl)-1,2-oxazol-3-yl]-1,2,4-oxadiazoles on heating in acetic acid.     

Synthesis and crystal structure of (4S,5R)-2-[2-(hydroxyethyl)imino]-3,4-dimethyl-5-phenyl-1,3-thiazolidine

Acid hydrolysis of l-N-[N′-(2-vinyloxy)ethylcarbamothioyl]ephedrine was studied. The synthesized (4S,5R)-2-[2-(hydroxyethyl)imino]-3,4-dimethyl-5-phenyl-1,3-thiazolidine was studied by means of X-ray diffraction.     

Synthesis of (5S)-5-methylfuran-2(5H)-one and its dihydro derivative

(5S)-5-Methylfuran-2(5H)-one and (5S)-5-methyltetrahydrofuran-2-one were synthesized starting from L-lactic acid ethyl ester.     

Synthesis and characterization of 2-alkyl -5-{4-[(3-nitrophenyl-5-isoxazolyl)methoxy]phenyl}-2H-tetrazoles

Heteroaryl substituted analogs of antirhnoviral (A), was prepared by a convergent approach. 3-Nitrophenyl-5- bromooromethylisoxazoles 5a–b were synthesized by [3+2] cycloaddition of 3-(benzoyloxy)-propyne 2 to in situ generated arylnitrile oxides followed by deprotection of cycloadducts 3a–b and bromination of the resulting alcohols 4a–b. Coupling of 3- nitrophenyl-5-bromooromethylisoxazoles (5a–b) with 4-[5-(2-alkyl-2H-tetrazolyl)]phenols (6a–d) in N-methylpyrrolidinone under mild conditions afforded a new series of 2-alkyl-5-{4-[1-(3-nitrophenyl-5-isoxazolyl)methyloxy]phenylr}-2H-tetrazoles (7a–h) in high yields. The structures of the synthesized compounds were confirmed by their ¹H NMR, Mass spectral, and Elemental Analysis data.     

Efficient synthesis of new 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrol-2(5H)-ones

The synthesis of 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrol-2(5H)-ones 5, 6a-d from 1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones 3, 4a-d is reported. The 1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones 3, 4a-d were obtained from regiospecific bromination of 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones 1, 2a-d with molecular bromine. The NMR and X-ray diffraction data showed that 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones were brominated at 4-position in the pyrrolidin-2-one ring.     

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.     

A facile synthesis of (Z)-5-(substituted)-2-(methylthio)thiazol-4(5H)-one using microwave irradiation and conventional method

A new effective approach to the synthesis of some new (Z)-5-(substituted)-2-thioxothiazolidin-4-one 3a–l and (Z)-5-(substituted)-2-(methylthio)thiazol-4(5H)-one 5a–l is reported under microwave irradiation as well as conventional conditions.     

Chemoenzymatic synthesis of (5S)- and (5R)-hydroxymethyl-3,5-dimethyl-4-(methoxymethoxy)-5H-thiophen-2-one: a precursor of thiolactomycin and determination of its absolute configuration

A convenient enantioselective synthesis of (5S)- and (5R)-hydroxymethyl-3,5-dimethyl-4-(methoxymethoxy)-5H-thiophen-2-one, a key intermediate in the synthesis of thiolactomycin has been carried out by a Carica papaya lipase-mediated resolution protocol to provide (R)-2 in a 94% ee and its enantiomer (S)-9 in a 98% ee. The absolute configuration at the C-5 position has been determined by Mosher’s method.     

Synthesis of lithium,sodium, cesium,and calcium salts of (E)-4- or (E,S)-3-methyl-2-(5-arylisoxazol-3-yl)-methyleneaminobutanoic, (E,S)-4-methyl-2- or (E,2S,3S)-3-methyl-2-(5-arylisoxazol-3-yl)methyleneaminopentanoic,and (E)-6-(5-arylisoxazol-3-yl)methyleneaminohexanoic acids

Preparative method for the synthesis of lithium, sodium, cesium, and calcium salts of (E)-4-(5-arylisoxazol-3-yl)methyleneaminobutanoic, (E)-6-(5-arylisoxazol-3-yl)methyleneaminohexanoic, (E,S)-3-methyl-2-(5-arylisoxazol-3-yl)methyleneaminobutanoic, (E,S)-4-methyl-2-(5-arylisoxazol-3-yl)methyleneaminopentanoic and (E,2S,3S)-3-methyl-2-(5-arylisoxazol-3-yl)methyleneaminopentanoic acids was developed by reacting 5-phenyl(4-tolyl)isoxazole-3-carbaldehydes with amino acids like 4-aminobutyric and 6-aminocaproic acids, L-valine, L-leucine or L-isoleucine in the presence of lithium hydride, sodium methoxide, cesium carbonate or calcium hydride in boiling methanol.     

Methyl (3R,5R)-3,5-dihydroxydecanoate in the asymmetric synthesis of Idea Leuconoe pheromone and formal syntheses of (+)-(3R,5R)-3-hydroxydecano-5-lactone, verbalactone, and Tolypothrix pentaether

A simple and efficient asymmetric synthesis of (5S,7R)-7-hydroxydodecano-5-lactone, a component of the giant danaine butterfly Idea leuconoe pheromone, and formal syntheses of (+)-(3R,5R)-3-hydroxydecano-5-lactone, verbalactone, and Tolypothrix pentaether have been accomplished starting from methyl (3R,5R)-3,5-dihydroxydecanoate. The latter is obtained from methyl 3-[(tributylstannyl)methyl]but-3-enoate using Keck allylation in the key step of the construction of its carbon skeleton.     

The application of (Z)-3-aryl-3-haloenoic acids to the synthesis of (Z)-5-benzylidene-4-arylpyrrol-2(5H)-ones

Studies directed at the synthesis of (Z)-5-benzylidene-4-arylpyrrol-2(5H)-ones from (Z)-3-aryl-3-haloenoic acids are described. The successful strategy relies on the preparation of (Z)-3-aryl-3-haloenoic acids from acetophenones through the corresponding (Z)-3-aryl-3-haloenals and the conversion of the (Z)-3-aryl-3-haloenoic acids to (Z)-5-benzylidene-4-aryl-5H-furan-2-ones. The furanones were subsequently treated with primary amines and dehydrated to the corresponding (Z)-5-benzylidene-4-arylpyrrol-2(5H)-ones.     

Synthesis of (−)-(5R,6S)-6-acetoxyhexadecan-5-olide by l-proline-catalyzed asymmetric aldol reactions

The natural mosquito attractant pheromone, (−)-(5R,6S)-6-acetoxyhexadecan-5-olide 1, was synthesized from readily available aldehyde 3 and cyclopentanone 4 using l-proline catalyzed asymmetric aldol reactions as the key step.     

Diels-Alder reactions of 3-(1H-tetrazol-5-yl)-nitrosoalkenes: synthesis of functionalized 5-(substituted)-1H-tetrazoles

A general route to 1,2-oxazines and open chain oximes bearing a 1H-tetrazolyl substituent via Diels-Alder reaction of 3-(tetrazol-5-yl)-nitrosoalkenes is reported. It was also demonstrated that reduction of these adducts followed by deprotection of the tetrazolyl group give 5-(1-aminoalkyl)-1H-tetrazoles, α-amino acid analogues.     

Synthesis,Structure, and Anti-influenza Activity of 2-(Adamantan-1-yl)-5-aryl-1,3,4-oxadiazoles and 2-(Adamantan-1-yl)-5-aryltetrazoles

Two series of new adamantyl derivatives of polynitrogen heterocycles, 2-(adamantan-1-yl)-5-aryl- 1,3,4-oxadiazoles and 2-(adamantan-1-yl)-5-aryl-2H-tetrazoles, have been synthesized, and their structure has been determined by NMR spectroscopy, mass spectrometry, and X-ray analysis. Biological studies in vitro have revealed high inhibitory activity of some of the synthesized 2-(adamantan-1-yl)-5-aryl-2H-tetrazoles against H1N1 influenza A viruses in combination with a relatively low selectivity.     

De novo designed contrasteric Diels-Alder reactions of 5-(2-oxazolynyl)-1,2,3,4,5-pentamethylcyclopentadiene

5-(2-Oxazolynyl)cyclopentadiene was designed on the basis of the orbital mixing rule to react with dienophiles with highly contrasteric manner in Diels-Alder reactions. The design was validated by the synthesis and reactions of the corresponding pentamethyl derivative, 5-(2-oxazolynyl)-1,2,3,4,5-pentamethylcyclopentadiene, to afford the products with the ratios of syn/anti=89-93/11-7.     

Conformational transformations and autooxidation of 5-bromo-2-(2-methylpropyl)-5-nitro-1,3,2-dioxaborinane

Conformational study of 5-bromo-2-(2-methylpropyl)-5-nitro-1,3,2-dioxaborinane at the DFT PBE/3ξ level of theory revealed the only sofa–sofa interconversion pathway through a transition state corresponding to 2,5-twist conformer. The barrier to internal rotation of the axial nitro group is several times higher than that for the equatorial nitro group. According to the ¹H, ¹³C, and ¹¹B NMR, IR, and X-ray diffraction data, the main autooxidation products of 5-bromo-2-(2-methylpropyl)-5-nitro-1,3,2-dioxaborinane are 2-bromo-2-nitropropane-1,3-diol and boric acid.     

Enantiospecific synthesis of the sugar amino acid (2S,5S)-5-(aminomethyl)-tetrahydrofuran-2-carboxylic acid

An enantiospecific synthesis of the tetrahydrofuran amino acid (2S,5S)-5-(aminomethyl)-tetrahydrofuran-2-carboxylic acid 1 is reported. The sugar enone 2-(S)-octyl 6-O-acetyl-3,4-dideoxy-α-d-glycero-hex-3-enopyranosid-2-ulose 2a, derived from galactose, was employed as a chiral precursor. The enone 2a was converted by chemical manipulation of the functional groups into the 6-azido-2-O-tosyl-3,4,6-trideoxy-d-erythro-hexono-1,5-lactone 9 as key intermediate. Methanolysis of 9 induced the opening of the lactone and the attack of the hydroxyl group at C-5 to C-2 with the displacement of the tosylate. This reaction led to the formation of the tetrahydrofuran ring of methyl (2S,5S)-5-(azidomethyl)-tetrahydrofuran-2-carboxylate 10, which was readily converted into 1. The overall yield of the sequence was 35%, and all the intermediates and the final product have been fully characterized. In addition, the preferential conformations in solution of lactone 9 and target molecule 1 have been established.     

Modified synthesis of methyl (1R,2R,3E,5R)-3-(hydroxyimino)-5-methyl-2-(1-methylethyl)-cyclohexanecarboxylate from (R)-4-menthen-3-one

A modified stereospecific synthesis of potentially biologically and pharmacologically active methyl (1R,2R,3E,5R)-3-(hydroxyimino)-5-methyl-2-(1-methylethyl)cyclohexanecarboxylate from (R)-4-menthen-3-one was developed using sequential 1,4-conjugate addition of Norman reagent catalyzed by CuI?CBF₃?Et₂O?CCuCl₂ and ozonolysis?Creduction of the intermediate (R,R,R)-vinylmenthone by hydroxylamine hydrochloridein MeOH.     

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.