Azetidine, structure

Azetidine itself has been studied by electron diffraction, which reveals a non-planar structure (Figure 1) (73CC772). The enhanced length of the bonds reflects the strain in the ring and the angle between the CCC and CNC planes of 37° is similar to that found for cyclobutane (35°), but quite different from that for oxetane (4°). 

S.09.3 AZETIDIN-2-ONES AND RELATED AZETIDINE DERIVATIVES 5.09.3.1 Structure... 

A wide variety of /3-lactams are available by these routes because of the range of substituents possible in either the ketene or its equivalent substituted acetic acid derivative. Considerable diversity in imine structure is also possible. In addition to simple Schiff bases, imino esters and thioethers, amidines, cyclic imines and conjugated imines such as cinnamy-lidineaniline have found wide application in the synthesis of functionalized /3-lactams. A-Acylhydrazones can be used, but phenylhydrazones and O-alkyloximes do not give /3-lactams. These /3-lactam forming reactions give both cis and /raMS-azetidin-2-ones some control over stereochemistry can, however, be exercised by choice of reactants and conditions. 

Azete, trisdimethylamino-isolation, 7, 278 Azetes, 7, 237-284, 278-284 benzo fused, 7, 278 benzodiazepine fused applications, 7, 284 fused ring, 7, 341-362 structure, 7, 360 2,3-naphtho fusion, 7, 278 reactivity, 7, 279 structure, 7, 278 synthesis, 7, 282-283 Azetidine, acylring expansion, 7, 241 synthesis, 7, 246 Azetidine, 3-acyl-irradiation, 7, 239 synthesis, 7, 246 Azetidine, N-acyl-synthesis, 7, 245 Azetidine, alkyl-synthesis, 7, 246 Azetidine, 3-alkylthio-synthesis, 7, 246 Azetidine, 3-amino-synthesis, 7, 246 Azetidine, N-amino-oxidation, 7, 241 synthesis, 7, 246 Azetidine, aryl-synthesis, 7, 246... 

Azetidin-2-one, l-benzyl-3,3,4-triphenyl-, 7, 249 Azetidin-2-one, l-(2-bromophenyl)-X-ray crystallography, 7, 247 Azetidin-2-one, 3-carboxy-synthesis, 7, 262 Azetidin-2-one, 3-halo-synthesis, 7, 77 ring contraction, 7, 81-82 Azetidin-2-one, 4-imino-IR spectroscopy, 7, 248 Azetidin-2-one, 1-phenyl-irradiation, 7, 255 Azetidin-2-one, 4-phenyl-reductive ring cleavage, 7, 252 Azetidin-2-one, 4-thio-IR spectroscopy, 7, 248 Azetidinones bicyclic, 7, 348-356 C NMR, 7, 348 H NMR, 7, 348 reactivity, 7, 356-358 spectroscopy, 7, 357 structure, 7, 349 synthesis, 7, 358-359 fused ring... 

A structurally unrelated agent is tazadolene (40). The synthesis of tazadolene begins with P-keto ester 37 and subsequent enamine formation with 3-amino-1-propanol followed by hydrogenolysis to give 38. This phenylhydroxymethyl compound is then dehydrated with hydrochloride acid to form olefin 39. Treatment with bromine and triphenylphosphine effects cycliza-tion to form the azetidine ring of tazadolene [10]. 

In addition to effects on biochemical reactions, the inhibitors may influence the permeability of the various cellular membranes and through physical and chemical effects may alter the structure of other subcellular structures such as proteins, nucleic acid, and spindle fibers. Unfortunately, few definite examples can be listed. The action of colchicine and podophyllin in interfering with cell division is well known. The effect of various lactones (coumarin, parasorbic acid, and protoanemonin) on mitotic activity was discussed above. Disturbances to cytoplasmic and vacuolar structure, and the morphology of mitochondria imposed by protoanemonin, were also mentioned. Interference with protein configuration and loss of biological activity was attributed to incorporation of azetidine-2-carboxylic acid into mung bean protein in place of proline. 

Azetidine ring is an important structure because it is present in many compounds of pharmaceutical interest however, its manipulation must be done very carefully owing to the reactivity of these heterocycles of small size. An interesting application of the use ofbiocatalytic processes is the resolution of azetidine esters (Scheme 7.11). The procedure to choose for the resolution of these compounds is the enzymatic ammonolysis of the corresponding N-substituted azetidines [26]. 

Cremer, D. 1981. Theoretical Determination of Molecular Structure and Conformation Part X. Geometry and puckering potential of azetidine, (CH2)3NH, combination of electron diffraction and ab initio studies. J. Mol. Struct. 75, 225-240. 

TABLE 2. Calculated (MM2 and MM3) and observed (ED and MW/ED) structure of azetidine (bond lengths in A, bond angles, 4v q and oj, in degrees see structure 3 for the definition of 4v q and ffl)5,6. Reprinted with permission from Refs. 5 and 6. Copyright (1985, 1990) American Chemical Society... 

TABLE 21. Selected structural parameters for dimethylamine, trimethylamine, 1,3,5,9-tetraazacyclohexadecane (7), azetidine (3) and nittomethane as calculated by UFF and MM2 and obtained from experiment58,59... 

A new electrolysis system comprising two metal redox couples, Bi(0)/Bi(III) and A1(0)/A1(III), has been shown to be effective for electroreductive Barbier-type allylation of imines [533]. The electrode surface structure has been correlated with the activity towards the electroreduction of hydrogen peroxide for Bi monolayers on Au(III) [578], Electroreductive cycliza-tion of the 4-(phenylsulfonylthio)azetidin-2-one derivative (502) as well as the allenecarboxylate (505) leading to the corresponding cycKzed compounds (504) and (506) has been achieved with the aid of bimetallic metal salt/metal redox systems, for example, BiCh/Sn and BiCh /Zn (Scheme 175) [579]. The electrolysis of (502) is carried out in a DMF-BiCh/Py-(Sn/Sn) system in an undivided cell by changing the current direction every 30 s, giving the product (504)in 67% yield. 

About 300 different non-protein amino acids occur in plants. They may be incorporated into proteins in place of the correct amino acids. If they are incorporated into enzymes, they can prevent them from functioning. This often leads to death of the animal. For example, azetidine 2-carhoxylic acid in lily-of-the-valley, Comallaria majalis, and several legumes interferes with synthesis or utilization of structurally similar proline (Fig. 11.9). 

Thietene is a liquid that polymerizes within an hour at room temperature. However, thietane, also a liquid, is more stable it exists as a puckered structure, similar to that of azetidine (note the sulfur atom and hence its lone-pair electrons occupy more space than those of oxygen). 

In addition to the 20 amino acids most frequently found in proteins a large group of amino acids occur in plants, bacteria, and animals that are not found in proteins. Some are found in peptide linkages in compounds that are important as cell wall or capsular structures in bacteria or as antibiotic substances produced by bacteria and fungi. Others are found as free amino acids in seeds and other plant structures. Some amino acids are never found in proteins. These nonprotein amino acids, numbering in the hundreds, include precursors of normal amino acids, such as homoserine and diaminopimelate intermediates in catabolic pathways, such as pipecolic acid d enantiomers of normal amino acids and amino acid analogs, such as azetidine-2-carboxylic acid and canavanine, that might be formed by unique pathways or by modification of normal amino acid biosynthetic pathways. 

Woodward s synthesis, 4, 416-419 Chlorophyll b, 4, 382 Chlorophyll c, 4, 382 Chlorophyll d, 4, 382 Chlorophylls, 4, 378 biosynthesis reviews, 1, 99 structure, 4, 370 substituents reactions, 4, 402 Chloroporphyrin e6, 4, 404 Chloroprothixene pharmacology, 3, 942 Chloropyramine as antihistamine, 1, 177 Chloropyrifos synthesis, 2, 201 Chloropyrifos-ethyl as insecticide, 2, 516 Chloropyrifos-methyl as insecticide, 2, 516 Chloroquine, 1, 145 adsorption on nucleic acids, 1, 179 as antimalarial, 1, 173, 2, 517 Chloroquine, hydroxy-as antimalarial, 2, 517 Chlorosulfonyl isocyanate cycloaddition reactions with alkenes, azetidin-2-ones from, 7, 261 reactions... 

Powdered crystals of 1, well ground and sandwiched by Pyrex glass plates, were irradiated with 500-W Hg lamp at 0 °C for 2 h, which led to the exclusive production of optically active / -thiolactam, l-benzyl-4-phenyl-azetidine-2-tliione-3-spiro-T-cyclohexane 2, in 96% yield at 58% conversion. The material was purified by column chromatography, and the structure was determined by spectroscopy. As expected, the thiolactam 2 showed optical activity ([a]D+109° c 1.0 CHC13, 94% ee). 

The discovery of the norcardicins and monobactams demonstrated for the first time that a conformationally constrained bicyclic structure was not necessary for antibacterial activity of (3-lactams [12, 13]. In recent years, various natural and unnatural monocyclic-(3-lactams have been shown to exhibit high biological activity, suggesting that the biological activity of the particular ring is influenced by the type of substitution attached to the azetidin-2-one ring (Fig. 2). 

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