Derivatives, vii

Anhalonine and Lophophorine. Spath and Gangl showed that each of these alkaloids contains a methylenedioxy group and that the quarternary iodide prepared from dZ-anhalonine is identical with lophophorine methiodide so that lophophorine must be N-methylanhalonine. Anhalonine was synthesised from 3 4-methylenedioxy-5-methoxybenzaldehyde by condensation with nitromethane, reduction of the product to the corresponding -ethylamine, the acetyl derivative (VII) of which, on treatment with phosphoric anhydride, condensed to 6-methoxy-7 8-methylenedioxy-l-methyl-3 4-dihydrofsoquinoline, m.p. 60-2°. This, on reduction, furnished the corresponding tetrahydrofsoquinoline, which proved to be anhalonine (VIII), and on conversion to the quaternary methiodide the latter was found to be lophophorine (IX) methiodide. The possible alternative, 8-methoxy-6 7-methylenedioxy-l 2-dimethyl-l 2 3 4-tetrahydrofsoquinoline, was prepared by Freund s method and the methiodide shown not to be identical with lophophorine methiodide. 

Results for these CEBEs are presented in Table 1. As can be seen, for the carvone variants I-V the various substitutions have absolutely no effect at the carbonyl C=0 core, and are barely significant at the chiral center that lies between the carbonyl and substituent groups in these molecules. Only upon fluorine substitution at the tail (molecule VI) does the C=0 CEBE shift by one-half of an electronvolt the second F atom substitution adjacent to the C=0 in the difluoro derivative, VII contributes a further 0.6-eV shift. This effect can be rationalized due to the electron-withdrawing power of an F atom. Paradoxically, it is these fluorine-substituted derivatives, VI, VII, that arguably produce b curves most similar to the original carvone conformer, I, yet they are the only ones to produce a perturbation of the ground-state electron density at the C li core. This contributes further evidence to suggest that, at least for the C li... 

Barker, S. A., and Bourne, E. J., Acetals and Ketals of the Tetritols, Pentitols and Hexitols, VII, 137-207 Barrett, Elliott P., Trends in the Development of Granular Adsorbents for Sugar Refining, VI, 205-230 Barry, C. P., and Honeyman, John, Fructose and its Derivatives, VII, 53-98... 

DMA in 500 ml ether mix rapidly with 270 ml 0.9 M phenyl-Li, boil fifteen hours and extract as for (VI) or as described previously to get 8 g oily 4-methoxy-indoline (or its 1-methyl derivative) (VII). Alternatively, add 36 g naphthalene to 300 ml tetrahydrofuran and add 11 g Na metal cut in small pieces. Reflux and stir three hours and add 18 g (VI) and 8 g DEA in 200 ml tetrahydrofuran rapidly and boil twelve hours. Evaporate in vacuum, dissolve the oily residue in 2N HCI and extract with ether. Proceed as described to get (VII). 4 g (VII) in 200 ml dry pyridine add to 6 g Cu chloride in 400 ml pyridine and reflux 1 xh hours. Pour on water and extract with ether. Wash extract with 4N HCI and then water and dry and evaporate in vacuum the ether to get 2 g of the indole (VIII). Alternatively, dissolve 4 g (VII) and 9.5 g cinnamic acid in 700 ml mesitylene, add 1 g 5% palladium-carbon and reflux five hours. Filter, wash with HCI and NaHC03 and dry and evaporate in vacuum the mesitylene to get the red, oily (VIII) (can chromatograph on alumina and elute with benzene-petroleum ether). 

On methylation of the disaccharide with dimethyl sulfate and sodium hydroxide a hexamethyl ether of the carbohydrate was obtained. When this fully methylated derivative (VII) was hydrolyzed with acid, 2,3,4,6-tetramethyl-D-glucose (VIII) and dimethyl-L-arabinose (IX) were produced. Since position 3 in the L-arabinose component of VI was shown to be occupied in glycosidic linkage with D-glucose, the dimethyl-L-arabinose could be either the 2,5- or 2,4-dimethyl derivative (IX),... 

VI) was hydrogenated to the corresponding sorbitol derivative (VII) in which the only groups unsubstituted were those situated at Cl and C4. Acid-catalyzed ring closure gave a product identical with the tetramethyl derivative of arlitan. 

If oxamidedioxime is treated with the mixed anhydride, the diformyl derivative VII is obtained, which can be cyclized into the 5,5 -unsubstituted dioxadiazole (VIII) by heating in the presence of BFj. 

No systematic efforts have apparently been undertaken to replace the carbon atoms of the above molecules by isolated hetero atoms or hetero atom-containing fragments. That this may, in fact, be a worthwhile undertaking is demonstrated by the /ert-butylimino derivative VII which is converted to a pyrrole (plus the other products shown in the scheme) by methyllithium. 

The purification of tetryl aims at removing by-products such as tetranitro derivative (VII), substances insoluble in benzene and the spent acid occluded by the crystals. The product is washed with cold water and then treated with hot water. This brings about the conversion of compound (VII) to (VIII)—the latter is soluble in hot water. The tetryl is then dissolved in benzene and insoluble constituents removed by filtration. The resulting solution is washed with water until it is completely free from acid. Alternatively, tetryl may be dissolved in acetone, precipitated with water, and finally deacidified. 

Melphalan has been converted to its trimethylsilyl derivative with bis(trimethylsilyl)acetamide and has been analyzed by GC on a 1.8 m x 3 mm column packed with 2.5% (w/w) SE-54 on acid-washed, silanized Chromosorb W (80-100 mesh) at 210° (injector temperature, 250° flame ionization detector temperature, 215°) using nitrogen as the carrier at 30 ml/min. The order of elution from a partly hydrolyzed mixture was melphalan, mono-hydroxy-derivative VI and di-hydroxy-derivative VII (Scheme III). The same elution order was obtained on a SE-30 column it was reversed on a more polar liquid phase (OV-17). Identification of the peaks was done by mass spectrometry [52]. 

M. Ando and S. Emoto, Catalytic activities of salicylaldehyde derivatives. VII. Synthesis and catalytic activity of (2-formyl-3-hydroxyphenyl)dime1hylsulfonium salt in the racemization of L-glutamic acid, Bull. Chem. Soc.. Jpn., 51, 2437-2438 (1978). 

Christensen (8) prepared acetic acid derivatives, (VII), which were effective as fatty acid synthase inhibitors useful in the treatment of gram-positive and gram-negative bacterial infections such as E. coli and S. aureus and S. epidermidis. 

Oxo-2,3-dihydro-indole derivatives, (VII), prepared by DeMello (6) had an especially favorable COX-H/COX-I selectivity ratio and used in treating inflammation disorders. 

Aminoalkyl-3, 4-dihydroquinoline derivatives, (VII), prepared by Jaroch (8) were effective as nitric oxide synthase inhibitors and used as anti-inflammatory agents. 

Tricyclic azaindolizine derivatives, (VII), effective as sPLA2 inhibitors were prepared by Fuji (8) and used in treating septic shock and adult respiratory distress syndrome. 

Pyridin-2-yl-amino)-thiazol-5-yl-aminomethyl derivatives, (VII), prepared by Borzilleri (7) inhibited the tyrosine kinase activity of growth factor receptors of VEGFR-2 and FGFR-1 and were useful as antiangiogenic agents. 

In a subsequent investigation by the author (7), cdk2/cyclin kinase inhibitors were prepared consisting of (5-bromo-l,3-thiazol-2-yl)amino derivatives, (VII), and were effective as cytotoxic agents without producing indiscriminate damage to both normal and tumor cells. 

In a subsequent investigation by the authors (6), 2-(4-bromo or 4-iodo phenylamino) benzoic acid derivatives, (VII), were prepared that were effective as inhibitors of MEK and used in treating cancer and other proliferative diseases. 

HT1A receptor antagonists consisting of 3-indolyl-4-piperidino heterocycles, (VI), and piperazine derivatives, (VII), with improved onset of action were prepared by Venkatesan (5) and Childers (6), respectively, and used in the treatment of depression and anxiety disorders. 

Arylamine polythiophene derivatives, (VII), were prepared by Okada [5] and used as thin film transitors. 

PiccineUi [5] used (tricyclopentylphosphine)dichloro(3-methyl-butenylidene), (VI), or related cyclic derivatives, (VII), to prepared anti-fog agents, (Vlll), by coupling 2-norbomene and aUyl-terminated ohgomeric ethylene oxide using ring opening metathesis polymerization as illustrated in (VIII) below. 

Week [4] prepared photoluminescent polynorborene derivatives, (VII), by polymerizing aluminum-8-hydroxyquinoline-functionalized norborene, (VI), using benzylidene (l,3-dimesitylimidazolydin-2-ylidene)-(tricyclohexylpho-sphine)ruthenium dichloride. 

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