Nitrile and amide biotransformations for the synthesis of enantiomerically pure 3-arylaziridine-2-carboxamide derivatives and their stereospecific ring-opening reactions

Catalyzed by Rhodococcus erythropolis AJ270 (whole cell catalyst) under very mild conditions, a number of racemic trans-3-arylaziridine-2-carbonitriles and amides were efficiently transformed into enantiopure 2R,3S-3-arylaziridine-2-carboxamides. While the nitrile hydratase exhibits low selectivity against nitrile substrates, the amidase is highly enantioselective toward 2S,3R-3-arylaziridine-2-carboxamides. Upon the treatment with catalytic hydrogenation, amine, or water in the presence of one equivalent of TFA, the resulting aziridine-2-carboxamides underwent highly efficient and stereospecific ring-opening reactions to produce enantiopure alpha-amino-, alpha,beta-diamino-, and alpha-amino-beta-hydroxy-propanamide derivatives in high yields.     

Synthesis of (−)-benzolactam-V8 by application of asymmetric aziridination

(?)-Benzolactam-V8, an artificially-designed cyclic dipeptide with strong tumor-promoter activity, was synthesized from benzyl (S)-N-(2-formylphenyl)-N-methylvalinate by application of guanidinium ylide-participated asymmetric aziridination followed by the reductive ring-opening reaction of 3-arylaziridine-2-carboxylate formed.     

Ring-opening reaction of unactivated 3-arylaziridine-2-carboxylates with nitrile reagents

Ring-opening reactions of unactivated 3-arylaziridine-2-carboxylates with nitrile reagents, using trans-1-benzyl-3-(3,4-methylenedioxyphenyl)aziridine-2-carboxylate as a typical aziridine substrate, were examined. Formation of azomethine ylide by C2-C3 bond cleavage was observed when the aziridine was treated with trimethylsilyl cyanide under thermal conditions. On the other hand the use of bromine cyanide (BrCN) and diethylaluminum cyanide (Et₂AlCN) led to N-C3 bond cleavage and the stereospecificity was found to be dependent on the reagent used. Additional aluminum-catalyzed ring-opening reactions disclosed that the potential cationic character of the C3 benzylic position and stereochemical requirements of substituents in the arylaziridine system control the reactivity. Furthermore, the synthetic utility of the ring-opening reaction was demonstrated not only by application to the cyclization of a ring-opened cyanopropanoate to an isoquinoline skeleton but also by the extension of other carbon nucleophile from nitrile (C1) to a ketene acetal (C2).     

Bacterial preparation of enantiopure unactivated aziridine-2-carboxamides and their transformation into enantiopure nonnatural amino acids and vic-diamines

[reaction: see text] Enantiopure (1R,2S)-1-benzyl- and 1-arylaziridine-2-carboxamides were obtained by kinetic resolution of their racemates by Rhodococcus rhodochrous IFO 15564 catalyzed hydrolysis. Several regio- and enantioselective nucleophilic ring openings of (1R,2S)-1-benzylaziridine-2-carboxamide or its LAH-reduced product led to a series of enantiopure products, such as O-methyl-l-serine and some vicinal diamines.     

Synthesis and characterization of benzyl and benzoyl substituted oxime-phosphazenes

Two oxime-cyclophosphazenes were prepared from hexakis(4-formylphenoxy)cyclotriphosphazene (2) and hexakis(4-acetylphenoxy)cyclotriphosphazene (7). The reactions of these oximes with benzyl chloride, benzenesulfanoyl chloride, benzoyl chloride, 4-methoxybenzoyl chloride and 2-chlorobenzoyl chloride were studied. Hexa and pentasubstituted compounds were obtained from the reaction of hexakis(4-[(hydroxyimino)methyl]phenoxy)cyclotriphosphazene (3) with benzyl chloride (4) and benzoyl chloride, respectively. However, the oxime groups on 3 rearranged to nitrile (5) in the reaction of 3 with benzenesulfanoyl chloride and 1-napthalenesulfanoyl chloride. Hexasubstituted compounds were also obtained from the reactions of hexakis(4-[(1)-N-hydroxyethaneimidoyl]phenoxy)cyclotriphosphazene (8) with benzoyl chloride (10), 4-methoxybenzoyl chloride (11) and 2-chlorobenzoyl chloride (12). A trisubstituted compound was obtained from the reaction of 8 with benzyl chloride (9). All the products were generally obtained in high yields. Pure and defined products could not be obtained from the reaction of 3 with 4-methoxybenzoyl chloride and 2-chlorobenzoyl chloride. The structures of the compounds were defined by elemental analysis, IR, ¹H, ¹³C and ³¹P NMR spectroscopy.     

A novel rearrangement of 2(5H)-furanones

A novel rearrangement of 2(5H)-furanones is described. When refluxed in aq. Ethanolic solution in the presence of excess KOH, the 2,5-dihydro-2-oxofuran-3-carboxamides 6 underwent a novel rearrangement to the corresponding 4,5-dihydro-4-oxo-2-(phenylamino)-3-furancarboxylic acids 1 in moderate-to-excellent yields.     

Naphthyridine studies. 15. 2-Styrylquinoline-3-carboxamides and their cyclization to 3-aryl-1-oxo-1,2,3,4-tetrahydrobenzo[b][1,6]naphthyridines

Condensation of 2-methylquinoline-3-carboxamides or the acid nitrile with benzaldehydes gave 2-styrylquinoline-3-carboxamides or the nitrile. It was shown that these compounds cyclize to the 2-substituted 3-aryl-1-oxo-1,2,3,4-tetrahydrobenzo[b][1,6]naphthyridines using pofyphosphoric acid or sulfuric acid.For Communication 14, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 92–94, January, 1992.     

Sacrificial azomethine ylide cycloaddition controlled chemoselective nitrile oxide cycloaddition to 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones: formation of mono-spiro-isoxazolines

The 1,3-dipolar cycloaddition of an azomethine ylide to 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones afforded novel spiro-pyrrolidines in good yields. Further cycloaddition of these spiro-pyrrolidines with nitrile oxide afforded mono-spiro-isoxazolines in moderate yields (45-56%), presumably via a di-spiro intermediate, which undergoes a spontaneous cycloreversion of the spiro-pyrrolidine unit. In contrast, the direct cycloaddition of nitrile oxide to 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones gave the mono-spiro-isoxazoline as the minor product, while the bis-spiro-isoxazolines are formed predominantly.     

Synthesis of condensed tetrahydroimidazo[1,2-a]quinazoline-1,5-dione derivatives

Heating of N-{2-[(R-amino)carbonyl]phenyl}prolinamides in triethyl orthoformate solution was found to give 6-R-5,6,6a,8,9,10,10a,11-octahydropyrrolo[1′,2′:3,4]imidazo[1,2-a]quinazoline-5,11-diones. Similar reaction of N-{2-[(R-amino)carbonyl]phenyl}thiazolidine-4-carboxamides afforded 6-R-5,6,6a,10,10a,11-hexahydrothiazolo[3′,4′:3,4]imidazo[1,2-a]quinazoline-5,11-diones. The relative configuration of C-6a and C-10a centres of the tetracyclic compounds obtained was assigned as trans on the basis of X-ray crystallographic study.     

A highly regio- and stereoselective nickel-catalyzed ring-opening reaction of alkyl- and allylzirconium reagents to 7-oxabenzonorbornadienes

[Reaction: see text]. An efficient method for the synthesis of cis-2-alkyl- or allyl-1,2-dihydronaphthalenes via a nickel-catalyzed highly regio- and stereoselective ring-opening addition of alkyl- or allylzirconium reagents to 7-oxabenzonorbornadienes is described. Treatment of 7-oxabenzonorbornadienes 1a-c with various alkylzirconium reagents 2a-j (Cp2ZrClCH2CH2R: R = tert-butyl, n-butyl, n-pentyl, -(CH2)3CH=C(CH3)2, -SiMe3, -CH2SiMe3, -(CH2)3Br, cyclopentyl, cyclohexyl, and benzyl) in the presence of NiBr2(dppe) and Zn powder in dry THF at 50 degrees C afforded the corresponding cis-2-alkyl-1,2-dihydronaphthalene derivatives 3a-m in good yields. In addition, allyl zirconium reagents 4a-c also underwent ring-opening reactions with 1a and 1c to give 5a-d in very good yields. The alkylative ring-opening products from 7-oxabenzonorbornadiene can be further converted to naphthalene derivatives 6a-c, via an acid-mediated dehydration, in good to excellent yields. A possible mechanism for the present catalytic reaction was proposed.     

Convenient Synthesis of 1,2,3,4-Tetrahydroisoquinoline-1-carboxylic Acid Derivatives via Isocyanide-Based,Three-Component Reactions

The three-component reactions of 3,4-dihydroisoquinolines, isocyanides, and benzyl chloroformate furnished 2-benzyloxycarbonyl-1,2,3,4-tetrahydroisoquinoline-1-carboxamides in moderate to good yields. Hydrogenolysis or selective hydrolysis of the benzyloxycarbonyl group provided 1,2,3,4-tetrahydroisoquinoline-1-carboxamides, further hydrolysis of which resulted in the corresponding 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acids.     

Catalytic Synthesis of N-Aryladamantane-1-carboxamides Using Phosphorus Trichloride

Russian Journal of Organic Chemistry - N-Aryl(benzyl)adamantane-1-carboxamides were synthesized in 54–87% yields by reaction of adamantane-1-carboxylic acid with aromatic amines in the...     

Synthesis and biological evaluation of Rhizobium sin-1 lipid A derivatives

A highly convergent strategy for the synthesis of several derivatives of the lipid A of Rhizobium sin-1 has been developed. The approach employed the advanced intermediate 3-O-acetyl-6-O-(3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-beta-d-glucopyrano-syl)-2-azido-4-O-benzyl-2-deoxy-1-thio-alpha-d-glucopyranoside (5), which is protected in such a way that the anomeric center, the C-2 and C-2' amino groups, and the C-3 and C-3' hydroxyls can be selectively functionalized. The synthetic strategy was used for the preparation of 2-deoxy-6-O-[2-deoxy-3-O-[(R)-3-hydroxy-hexadecanoyl]-2-[(R)-3-octacosanoyloxy-hexadecan]amido-beta-d-glucopyranosyl]-2-[(R)-3-hydroxy-hexadecan]amido-3-O-[(R)-3-hydroxy-hexadecanoyl]-alpha-d-glucopyranose (11) and 2-deoxy-6-O-[2-deoxy-3-O-[(R)-3-hydroxy-hexadecanoyl]-2-[(R)-3-octacosanoyloxy-hexadecan]amido-beta-d-glucopyranosyl]-2-[(R)-3-hydroxy-hexadecan]amido-3-O-[(R)-3-hydroxy-hexadecanoyl]-d-glucono-1,5-lactone (13), which contain an unusual octacosanoic acid moiety and differ in the oxidation state of the anomeric center. The results of biological studies indicate that 11 and 13 lack the proinflammatory effects of Escherichia coli lipopolysaccharides (LPS). Furthermore, 13 emulated the ability of heterogeneous R. sin-1 LPS to antagonize enteric LPS, providing evidence for the critical role of the gluconolactone moiety of R. sin-1 LPS in mediating this antagonistic effect. Compound 13 is the first example of a lipid A derivative that is devoid of phosphate but possesses antagonistic properties, making it an attractive lead compound for development of a drug to use in the treatment of Gram-negative septicemia.     

Ruthenium-catalyzed ROM-RCM of cycloalkene-yne

[formula: see text] ROM-RCM (ring-opening and ring-closing metatheses) of cycloalkene-yne was demonstrated using a second-generation ruthenium complex. When cycloalkene bearing the alkyne moiety at the C-1 position was reacted with a ruthenium-carbene complex under an atmosphere of ethylene, ROM-RCM proceeded smoothly to give bicyclic compound and/or dimeric compound in good yields.     

Sequential 1,3-Dipolar Cycloadditions in the Synthesis of Novel Tri-spiro Cyclohexanones and Piperidin-4-ones

The sequential 1,3-dipolar cycloadditions of azomethine ylide and nitrile oxide to a series of 2,6-bis[(E)-arylmethylidene]cyclohexanones and 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones afforded novel tri-spiro heterocycles comprising isoxazoline, pyrrolidine and acenaphthylen-1(2H)-one rings in good yields and stereoselectivity.     

A new strategy for the synthesis of 1,4-benzodiazepine derivatives based on the tandem N-alkylation-ring opening-cyclization reactions of methyl 1-arylaziridine-2-carboxylates with N-[2-bromomethyl(phenyl)]trifluoroacetamides

A new method for the synthesis of novel 1,4-benzodiazepine derivatives has been established from a one-pot reaction of methyl 1-arylaziridine-2-carboxylates with N-[2-bromomethyl(aryl)]trifluoroacetamides. The reaction proceeds through the N-benzylation and highly regioselective ring-opening reaction of aziridine by bromide anion followed by Et3N-mediated intramolecular nucleophilic displacement of the bromide by the amide nitrogen. The easy availability of starting materials, simple and convenient synthetic procedure, and formation of functionalized 1,4-benzodiazepine scaffold ready for further chemical manipulations render this strategy useful in synthetic and medicinal chemistry.     

New One‐Pot Three‐Component Synthesis of N‐Phenyl α‐Aminophosphonates

New one‐pot three‐component reactions employing aldehydes, triphenylphosphite, and N‐[(phenylamino)carbonyl]glycine ethyl ester in refluxing xylene readily afford N‐phenyl α‐aminophosphonates in low to moderate yields.     

A novel oxamide rearrangement

An efficient, base-induced rearrangement of 2-[(1,2-dioxo-2-(methylamino)ethyl)phenylamino]benzoic acid methyl ester ( 7a ) to the isomeric 2-[(1,2-dioxo-2-(phenylamino)ethyl)methylamino]benzoic acid methyl ester ( 27a ) is described. This novel rearrangement must proceed through a spiro intermediate wherein benzoate is acting as a Michael receptor. When 2-[(1,2-dioxo-2-(methylamino)ethyl)methylamino]benzoic acid methyl ester ( 28 )-an oxamide which would produce a degenerate spiro intermediate — was subjected to rearrangement conditions, the product obtained was 1,3-dimethyl-2,4-(1H,3H)quinazolinedione ( 29 ). This latter transformation may have proceeded via a benzodiazepinetrione intermediate.     

Midrange affinity fluorescent Zn(II) sensors of the Zinpyr family: syntheses, characterization, and biological imaging applications

The syntheses and photophysical characterization of ZP9, 2-{2-chloro-6-hydroxy-3-oxo-5-[(2-{[pyridin-2-ylmethyl-(1H-pyrrol-2-ylmethyl)amino]methyl}phenylamino)methyl]-3H-xanthen-9-yl}benzoic acid, and ZP10, 2-{2-chloro-6-hydroxy-5-[(2-{[(1-methyl-1H-pyrrol-2-ylmethyl)pyridin-2-ylmethylamino]methyl}phenylamino)methyl]-3-oxo-3H-xanthen-9-yl}benzoic acid, two asymmetrically derivatized fluorescein-based dyes, are described. These sensors each contain an aniline-based ligand moiety functionalized with a pyridyl-amine-pyrrole group and have dissociation constants for Zn(II) in the sub-micromolar (ZP9) and low-micromolar (ZP10) range, which we define as "midrange". They give approximately 12- (ZP9) and approximately 7-fold (ZP10) fluorescence turn-on immediately following Zn(II) addition at neutral pH and exhibit improved selectivity for Zn(II) compared to the di-(2-picolyl)amine-based Zinpyr (ZP) sensors. Confocal microscopy studies indicate that such asymmetrical fluorescein-based probes are cell permeable and Zn(II) responsive in vivo.     

Rhodium-Catalyzed Asymmetric Conjugate Additions of Boronic Acids to enones using DIPHONANE: a novel chiral bisphosphine ligand

[reaction: see text] The synthesis of a novel enantiopure C2-symmetric bisphosphine, DIPHONANE, was accomplished starting from 2,5-norbornadione, utilizing (R,R)- and/or (S,S)-(2,3-O-di[(phenylamino)carbonyl]tartaric acid for the resolution of an intermediate phosphineoxide. The application of this ligand in the rhodium-catalyzed asymmetric conjugate addition of boronic acids to cyclic enones provides the 1,4-addition products in good yields (69-98%) and high ee's (78-95% ee). A byproduct arising from a consecutive 1,4-addition and 1,2-addition was also observed.