Showing papers on "Bicyclic molecule published in 1979"

Developments in Arylnitrene Chemistry: Syntheses and Mechanisms [New synthetic methods (31)]

Abstract: Aryl- and heteroaryl-nitrenes can take part in intra-and intermolecular reactions in both of their possible electronic states (triplet and singlet). In this review we have endeavored to high-light recent synthetic uses of these reactive intermediates as well as draw attention to avenues open to further exploration in this field. Singlet arylnitrenes will interact with suitable ortho-positioned substituents to give a variety of fused azoles, some in excellent yield. In suitable solvents and in presence of amines and alcohols, phenylnitrenes undergo ring expansion to azepines which can also occur in nitrenes of certain fused bicyclic aromatics (naphthalene, quinoline, isoquinoline, benzo[b]thiophene). The latter nitrenes may also give rise to o-diamines which are useful starters for further heterocyclic synthesis. Triplet arylnitrenes (usually regarded as having only a nuisance effect in synthetic work) may also be utilized in practicable heterocyclic syntheses within a suitable molecular framework. Decomposition of aryl azides in a mixture of an organic and polyphosphoric acid leads to fused oxazoles. The mechanism is discussed for all the reactions considered.

Cobalt-catalyzed one-step synthesis of annulated pyridines

Abstract: A method of synthesizing fused ring pyridines (annulated) by co-oligomerization of α,ω-diynes with about molar equivalents of nitriles using a Co+1 catalyst preferably cyclopentadienyl cobalt dicarbonyl. Additionally, new compounds of tricyclic quinolizine-4-ones were produced where excess cyanoacetic ester starting materials were utilized (about 2:1 equivalent nitriles:diyne). The results with the catalyst employed indicated a stepwise mechanism in which cobalt(I) catalyst first forms a metallocycle intermediate derived from the bisacetylene. This cobalt(III) intermediate reacts preferentially with nitriles to give the product annulated pyridines in good yield. Generally, preferred conditions indicated roughly molar equivalents of reactants with no substantial excess of either reactant for the bicyclic compounds. Preferred conditions include a moderate temperature (solvent reflux temperature) and a preferred solvent such as BTX-type solvent (xylene) or an alkane (N-octane) under an inert blanket (nitrogen) for a multi-day period.

Synthesis of anatoxin a via intramolecular cyclization of iminium salts

Abstract: Anatoxin a (1) has been synthesized by exploiting intramolecular cyclization between an iminium salt and a nucleophilic carbon to construct the 9-azabicyclo(4.2.1)nonane ring system. Cyclization of malonate iminiumsalt 16 at alkaline pH afforded a low yield of bicyclic malonate 18 owing to an unfavorable equilibrium constant and lability of the iminium salt in base. In contrast, cyclization of ketoiminium salt 31 afforded a good yield of bicyclic ketone 34 in acidic methanol. Dihydropyrrolium salts 16 and 31 were generated quantitatively by decarbonylation of substituted N-methylprolines 15 and 30b, obtained by reduction of the corresponding pyrroles.

Thermische Cyclisierung von α‐Alkinonen zu 2‐Cyclopentenonen

Abstract: Thermal Cyclization of α-Alkynones to 2-Cyclopentenones Gas phase thermolysis at 600–740° of substituted 1-pentyn-3-ones (α-alkynones), which are easily prepared by acylation of trimethylsilyl acetylenes, leads to substituted 2-cyclopentenones. The intramolecular formation of a new C, C-bond between an acetylenic and a non-activated carbon atom is accompanied by a [1,2]-migration of one of the substituents at the triple bond. This novel ‘-alkynone cyclization’ reaction may be explained by postulating an alkylidene carbene intermediate which inserts into a C,H-bond five carbon atoms away at the non-acetylenic part of the ketone. Several examples demonstrate that the α-alkynone cyclization offers a simple tool for the preparation of certain monocyclic, bicyclic and spiro compounds containing a 2-cyclopentenone moiety.

Cyclic amidine inhibitors of indolamine N-methyltransferase.

Abstract: Syntheses of a large number of mono- and bicyclic, as well as a few tricyclic, amidine derivatives related to 2,3,4,6,7,8,-hexahydropyrrolo[1,2-a]pyrimidine (DBN) are reported. In vitro potencies for inhibition of the enzyme indolamine N-methyltransferase (INMT) from rabbit and human lung are presented. Four bicyclic amidine derivatives and 11 monocyclic derivatives were found to be equal or superior to DBN in in vitro potencies. With the bicyclic amidines, increasing ring size or introduction of substituents reduced activity. Among the monocyclic analogues, the most potent representatives were five- or six-membered systems with an exocyclic imino group, combined with methyl of ethyl substituents on the endocyclic nitrogen. Introduction of additonal substituents decreased inhibitory potency. 2,3,5,6-Tetrahydro-8H-imidazo[2,1-c][1,4]thiazine and 3-methyl-2-iminothiazolidine have been shown to cause inhibition of lung INMT when administered orally to rabbits.

Structural and conformational analogues of L-methionine as inhibitors of the enzymatic synthesis of S-adenosyl-L-methionine. IV. Further mono-, bi- and tricyclic amino acids.

Abstract: A series of mono-, bi- and tricyclic amino acids was synthesized and examined for their ability to inhibit the enzymatic conversion of L-methionine to S-adenosyl-L-methionine by partially purified preparations of ATP:L-methionine S-adenosyltransferase (EC 2.5.1.6) of bakers’ yeast, Escherichia coli and rat liver. These studies are part of a program to define the topography of the amino acid binding site of these enzymes and to design selective inhibitors of potential chemotherapeutic value. The synthetic amino acids are structurally and conformationally related to 1-aminocyclopentane-1-carboxylic acid (cycloleucine), a highly effective inhibitor of S-adenosyl-L-methionine formation. They were designed to provide more precise information about the space-filling and conformational requirements for complementarity at the active sites of the enzymes. Cyclopentaneglycine, although less inhibitory than cycloleucine, has modest activity that is attributed to its conformational relationship to the highly active (1R,2R,4S)-isomer of 2-aminonorbornane-2-carboxylic acid. The (1R,2R,4S)-isomer of 2-amino-5,6-exo-trimethylenenorbornane-2-carboxylic acid appears to be a more potent inhibitor than its 2-aminonorbornane-2-carboxylic acid analogue. It is presumed that the 5,6-exo-trimethylene extension of the norbornane framework increases binding capacity because of positive hydrophobic interactions with the enzyme surface in this region. The most active enzyme inhibitor found in this study was (+)-2-aminobicyclo[2.1.1]hexane-2-carboxylic acid, which was even more potent than its close structural analogue, the active 2-aminonorbornane-2-carboxylic acid isomer. This enhancement of inhibitory activity may be a reflection of the size of the bridgehead angle of the bicyclo[2.1.1]hexane derivative which is almost 7° smaller than the corresponding bridgehead angle of the norbornane derivative, and apparently contributes to a more precise complementarity of the bicyclo[2.1.1]hexane amino acid at the surface of the enzyme. The idea that this internal bridgehead angle must not exceed a critical value if binding is to occur is further supported by the fact that the analogous isomer of 2-aminobicyclo[3.2.1]octane-2-carboxylic acid, which has an internal bridgehead angle 6° larger than the norbornane derivative, is inactive. Other amino acids which have contributed to the elucidation of the conformational requirements of the enzyme active site include 7-aminonorbornane-7-carboxylic acid, 3-aminonortricyclene-3-carboxylic acid, 1-amino-2,5-dimethylcyclopentane-1-carboxylic acid, 1-amino-3,4-dimethylcyclopentane-1-carboxylic acid and 3-aminobicyclo[3.2.0]heptane-3-carboxylic acid; the latter analogue possessed significant inhibitory activity.

Aromatic systems with 10π electrons derived from 3a-azapentalene. Part 37. Cyclization of the anion of azido-s-triazole into the anion of s-triazolo[2,3-d]tetrazole

Abstract: Two N-methyl derivatives of a novel bicyclic system with 10π electrons derived from 3a-azapentalene, s-triazolo[2,3-d]tetrazole, have been synthesized and their structures established by comparison with known isomeric systems using 1H and 13C n.m.r., i.r., and mass spectra. Isomerization of the anion of azido-s-triazole to the anion of s-triazolo[2,3-d]tetrazole is confirmed.

Radical cyclocopolymerization of divinyl ether and maleic anhydride. A 13C‐NMR study of the polymer structure

Abstract: The structure of the 1:2 copolymer of divinyl ether and maleic anhydride was investigated by 13C-NMR spectroscopy. The polymer contains the bicyclic unit composed of one molecule of each monomer and the maleic anhydride unit. The carbon chemical shift for these units was calculated on the basis of the chemical shift of many model compounds. The major peaks of the cyclopolymer prepared in chloroform were consistent with the presence of the symmetrical bicyclic unit with cis junction and the trans monocyclic anhydride unit. The carbonyl carbon spectrum for the copolymer obtained in a mixed solvent of acetone and CS2 suggested the predominant formation of the unsymmetrical bicyclic unit. The polymerization process was discussed on the basis of these results.

Iminyls. Part 3. Formation of triaryl-pyridines and -pyrimidines from aryl-β-arylvinyliminyls

Abstract: Aryl-β-arylvinyliminyls, produced by oxidation of the corresponding imino-oxyacetic acids with persulphate or by thermolysis of the t-butyl peresters of these acids, abstract hydrogen giving imines which dimerise and/or are hydrolysed to ketones. The bicyclic dimers so formed readily undergo oxidative fragmentation to triaryl-pyridines and/or -pyrimidines.

Bicyclic heterocyclic amino derivatives

Abstract: The present invention concerns compounds of formula ##STR1## wherein X is O, S or NH; n is 1 or 2 and A is a 5-membered heterocyclic ring, wherein the bicyclic system may be substituted. The compounds are useful as myotonolytic and anti-hypertensive agents.

Five-membered ring annelation via thermal rearrangement of β-cyclopropyl-αβ-unsaturated ketones: a new total synthesis of (±)-zizaene

Abstract: The bicyclic αβ-unsaturated ketone (2), conveniently prepared by thermal rearrangement of (1), is converted, via an 11-step sequence, into the tricyclic ketone (15), thus formally completing a new total synthesis of (±)-zizaene (3).

Cyclic guanidines. IV. Synthesis of hypoglycemic N-benzhydryl bicyclic guanidines.

Abstract: Synthesis of N-benzhydryl bicyclic guanidines (12) was attempted The key intermediates, 1-benzhydryl-2-N- or 3-(ω-hydroxyalkyl)-2-imino-1, 3-diazacycloalkanes (4) and (9) were prepared The intramolecular cyclization of 4 to 12 was not advantageous because of the low yield On the other hand, the intramolecular cyclization of 9 to 12 resulted in good success In our synthetic course, imidazo [1, 2-a] [1, 3, 5] oxadiazocine derivative (11), a new ring system, and N1-benzhydryl-N1-[2-(1-pyrrolidinyl) ethyl] urea (13) were isolated as by-products The N-benzhydryl bicyclic guanidines (12) showed potent hypoglycemic activity

Bicyclic somatostatin analogs

Abstract: Bicyclic somatostatin analogs and pharmaceutically acceptable non-toxic acid addition salts thereof are prepared by a combination of the solid phase method and the solution method. These analogs have the property of inhibiting the release of insulin, glucagon and growth hormone in humans and animals. The compounds are particularly useful in the treatment of diabetes. Due to the bicyclic structure, these analogs are resistant to enzymatic metabolism and have a longer duration of activity.

Cyclic Guanidines. V. Synthesis of Hypoglycemic 2, 2- and 3, 3-Diphenylimidazo [1, 2-a] [1, 3]-diazacycloalkane Derivatives

Abstract: Synthesis of 2, 2- and 3, 3-diphenylimidazo [1, 2-a] [1, 3] diazacycloalkane derivatives (4) and (5) was attempted. The cyclization of 2-(ω-chloroalkylimino)-4, 4-diphenylimidazolidines (3) was not advantageous because it gave a mixture of 4 and 5 in low yield. 5, 5-Diphenylhydantoin (6) was alkylated at the N3 or O2 position and successive reduction of the remained carbonyl group of the products resulted in success. The 3-N-alkylated compounds (14) prepared from 6 selectively gave 4. The 2-O-ethyl derivative (19) afforded 2-(ω-chloroalkylimino) derivatives (21). Heating 21 gave 2-oxo-bicyclic guanidines (22), and treatment of 21 with sodium hydride yielded 3-oxo-bicyclic guanidines (17) in good yield, respectively. Sodium bis (2-methoxyethoxy) aluminum hydride reduction of 17 and 22, having a carbonyl group in the molecule, gave 4 and 5, respectively. Under the same conditions, N-methyl-2-oxo- or 3-oxo-bicyclic guanidines (18) and (28) gave partially reduced products. The bicyclic guanidines (4) and (5) showed potent hypoglycemic activity.

Helical canal inclusion complexes formed by a bicyclic diol; X-ray crystal structure of exo-2, exo-6-dihydroxy-2,6-dimethylbicyclo[3.3.1]nonane–ethyl acetate inclusion complex

Abstract: An X-ray crystal structure determination shows that, as a consequence of helices of hydrogen bonds, crystalline exo-2,exo-6-dihydroxy-2,6-dimethylbicyclo[3.3.1]nonane comprises a network of separate helical canals, lined only with hydrocarbon hydrogen atoms, which trap a variety of guest molecules.

Bicyclo [3. 3. 1]nonanes as Synthetic Intermediates. IV. Behavior of Bicyclo [3. n. 1] alkan-3-ones toward the Baeyer-Villiger Oxidation

Abstract: The Baeyer-Villiger oxidation of bicyclo [3. n. 1] alkan-3-ones and related systems is described. Bicyclo [3. 3. 1] nonan-2-one (8) was oxidized into the corresponding lactone, which was found to be converted into the cis-1, 3-disubstituted cyclohexane system by the subsequent methanolysis. Meanwhile, the 3-oxo system (2) manifested an anomalous inactivity against the oxidation. The"backside steric hindrance"caused by the axial (endo) proton at C-7 was postulated as the origin of the inactivity. The differential reactivity of the ketones in the Baeyer-Villiger reaction of the bicyclic systems (2, 3, 4) enabled the regiospecific lactonization of the bicyclic diketones (17, 18, 19) into the lactones (37, 38, 39), which would be important precursors for specifically substituted medium-sized lactones, to be achieved.

Further studies on metal-promoted vinylcyclopropane to cyclopentene rearrangements. Structure and thermolysis of rhodium complexes of exo-6-vinylbicyclo[3.1.0]hex-2-ene and the crystal structure of the 1,6–8-η4-5-allylcyclopent-2-enyl(hexafluoroacetylacetonato)rhodium(III) tetramer

Abstract: The reactions of exo-6-vinylbicyclo[3.1.0]hex-2-ene with bis(ethylene)rhodium(I) complexes lead to displacement of ethylene and formation of ring-opened σπ-bis-allylrhodium derivatives. The hexafluoroacetylacetonate (11) is tetrameric in the solid state and its structure has been determined by X-ray methods. Crystals of [C13H11F6RhO2]4 are monoclinic, space group P21/c, a= 19.641(7), b= 14.353(7), c= 44.87(1)A, β= 98.03(3), Z= 8; 3 266 observed reflections [I/σ(I) > 3.0] were collected by diffractometer and refined to R 0.077.The four rhodium atoms form the corners of a puckered square and are each π-bonded to one hydrocarbon at C(2),C(3) and to another σ at C(1) and π at C(6)–(8). This complex rearranges in acetone solution at 338 K, mainly to the corresponding derivative of bicyclo[3.3.0]octa-2,6-diene; thermolysis of the corresponding dimeric acetylacetonate (12) has been studied in detail by 1H n.m.r. The reaction exhibits half-order kinetics over the conentration range 0.02–0.2M in deuteriobenzene, rearranging rapidly (t1/2[0.205M] 30.30 min) to a mixture of acetylacetonato(bicyclo[3.3.0]octa-2,6-diene)rhodium(I)(2) and acetylacetonato-(endo-6-vinylbicyclo[3.1.0]hex-2-ene)rhodium(I)(1) in 88 : 12 ratio. In deuteriodichloromethane, the ratio is 33 : 67. The cyclopentadienyl complex (14) is monomeric, and thermally stable below 373 K. Reaction of the rhodium chloride complex (13) with bicyclo[2.2.1]hepta-2,5-dienesilver hexafluorophosphate leads directly to a rearranged cation (17) at 273 K.The mechanisms of these transformations are discussed.