Indoles. I. Syntheses of 1-Acetyltryptophan and Its Derivatives, and Their Friedel-Crafts Reaction

Ohki, Sadao; Nagasaka, Tatsuo

doi:10.1248/cpb.19.545

Cited by 12 publications

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“…(Z)-Methyl (9-methyl-3-oxothiazolo[3,2-a ]indol-2(3ff)ylidene)acetate (2b) was obtained from Id by the same procedure described above in 62% yield: mp 197-198 °C; UV (CHC13) XmM 436 nm (log e 3.85), 287 (4.41); IR (KBr) 1730, 1695 cm-1; NMR (CDC13) 2.20 (s, 3 H), 3.86 (s, 3 H), 6.95 (s, 1 H), 7.15-7.50 (m, 3 ), 7.89-8.13 (m, 1 H); mass spectrum, m/e (rel intensity) 275 (6), 274 (14), 273 (M+, 100), 242 (8), 214 (7).…”

Section: Methodsmentioning

confidence: 99%

“…The solvent was then removed under reduced pressure, and the white residue was crystallized from carbon tetrachloride-chloroform to give 7b in 94% yield: mp 262-263 °C; NMR (Me2SO-d6, HMDS) 2.28 (s, 9 H, 3 CH3), 2.88 (s, 3 H, CH3S02), 7.0-8.2 (3 m, 9 aromatic H); mass spectrum, m/e (rel intensity) 451 (0.2, M+•), 387 (52, +• -S02), 372 (6, +• -CH3S02), 310 (6, M+. -PhS02), 308 (100, M+• -S02 -CH3S02), 173 (55), 149 (8, CIH3C6H4NCS+•), 131 (14,CH3C6H4NCN+). Anal. Caled for C19H21N304S3 (mol wt 451): C, 50.55; H, 4.66; N, 9.31.…”

Section: Notesmentioning

confidence: 99%

“…Found: C, 60.69; H, 6.73; N, 11.20. Reaction of 1 with Diphenylketene. A solution of 1 (0.002 mol) and a threefold excess of diphenylketene in 5 mL of dry chloroform was stirred at: room temperature for 7 h. After removal of the solvent the residue was chromatographed on silica gel with ether-hexane as the eluent to give 8b in 98% yield: mp 151-152 °C (ether-hexane); NMR (CDC13) 2.00 (s, 6 H, 2 CH3), 2.18 (s, 3 H, CH3), 2.84 (s, 3 H, CH3S02), 6.6-7.4 (2 m, 14 phenylsulfonyl isocyanate, 2845-62-7; phenyl isocyanate, 103-71-9; benzoyl isocyanate, 4461-33-0; benzamide, 55-21-0; carbethoxy isothiocyanate, 16182-04-0; phenylsulfonyl isothiocyanate, 1424-53-9; íert-butylcyanoketene, 29342-22-1; 2,5-di-tert-butyl-3,6-diazidobenzoquinone, 29342-21-0; diphenylketene, 525-06-4.…”

Section: Notesmentioning

confidence: 99%

“…Facile Entry into the Thiazolo[3,2-a]indol-3(2Jf)-one System via an Unusual Reaction with Thionyl Chloride1® Received May 14,1979 During the course of our synthetic investigations into the canthin-6-one series2 we treated 7-oxo-3-[(methoxycarbonyl)methyl]-lff-indole-1-butanoic acid (la) with oxalyl chloride to give the acid chloride lb which was used without isolation in a Friedel-Crafts intramolecular cyclization. However, similar reaction of la with refluxing thionyl chloride followed by methanol treatment did not give the expected methyl ester lc but instead gave orange fibrous needles of 2a in 20% yield.…”

Section: Notesmentioning

confidence: 99%

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Facile entry into the thiazolo[3,2-a]indol-3(2H)-one system via an unusual reaction with thionyl chloride

Showalter

Shipchandler²,

Mitscher³

et al. 1979

J. Org. Chem.

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Section: Methodsmentioning

confidence: 99%

Section: Notesmentioning

confidence: 99%

Section: Notesmentioning

confidence: 99%

Section: Notesmentioning

confidence: 99%

See 2 more Smart Citations

Facile entry into the thiazolo[3,2-a]indol-3(2H)-one system via an unusual reaction with thionyl chloride

Showalter

Shipchandler²,

Mitscher³

et al. 1979

J. Org. Chem.

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“…( + 2,2-! (Jennings 1957;Ohki & Nagasaka 1971;Nagasaka & Ohki 1977;Ishizumi et al 1967). (Teranishi et al 1995).…”

Section: 6mentioning

confidence: 99%

Σύνθεση Νέων Ετεροκυκλικών Χημειοτύπων Με Πιθανή Φαρμακοθεραπευτική Χρησιμότητα Στην Αντιμετώπιση Της Κατάθλιψης Και Των Χρόνιων Επιπλοκών Του Σακχαρώδη Διαβήτη. Βιοχημική Και Υπολογιστική Προσέγγιση

Ζήκα¹,

Zika²

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The present work is divided to two parts: 1) Applied Pharmacochemistry and 2) Computational Pharmacochemistry 1) Applied Pharmacochemistry: New heterocyclic chemotypes are synthesized that are derivatives of: i) the octahydroindolquinoline that may be useful for the pharmacotherapy of depression and ii) 2,4- and 2,5- substituted pyrroles that may be useful for the pharmacotherapy of the chronic complications of diabetes mellitus. These structures were designed based on molecular modeling methods. Their biological profile was studied based on biochemical models. For the synthesis of the compounds, known reactions, appropriately modified, were applied as well as novel synthetic procedures were developed. The aim was to find simple and efficient methodologies for the synthesis of the compounds. A total of 4 target compounds were isolated, one of them is an indole derivative and the others are pyrrole derivatives. Furthermore, 36 intermediates were synthesized, from which 25 are new compounds, 7 are pyrrole derivatives and 18 are indole derivatives. a) The synthesis of the tetracyclic compound, which is an indole derivative, involves a successful cyclization at the 4-position of the indole ring. This is carried out using a novel Friedel-Crafts cyclization system. The new indole derivative was tested in vitro for its affinity for serotonin receptors (5-HT1A, 5-HT2A and 5-HT1C) and dopamine receptors (D1 and D2). It was found that the compound acts mainly at 5-HT2C receptors whereas it expresses no binding affinity at dopamine receptors. Also, it was tested in vitro for its ability to inhibit the enzyme aldose reductase and to inhibit in vitro the irreversible modification of proteins. The above three in vitro models are related to depression and the results demonstrate desirable biological properties for the pharmacotherapy of mood disorders. Finally, it was tested ex vivo for its intestinal permeability while its polar molecular surface area was calculated. These two parameters are related to passive permeability through biomembranes. Taken together, the above results indicate that the compound could be given per os and it could penetrate the blood brain barrier. b) The synthesis of the pyrrole derivatives was carried out based on Friedel- Crafts acylations. It was found that, for these reactions, the presence of nitromethane was necessary. Intramolecular aroyl migration was also observed and a possible mechanism is proposed. The new pyrrole derivatives were tested in vitro for their ability to inhibit the enzyme aldose reductase. It was found that two of them are strong inhibitors in nanomolar concentrations. The compound that was found to be the more potent aldose reductase inhibitor was studied for its ability to inhibit in vitro the irreversible modification of proteins. It was found to be as effective as trolox. 2) Computational Pharmacochemistry: A number of physicochemical properties were calculated for several molecules with different structures. For the calculation of a number of physicochemical properties, a Monte-Carlo conformational search was first performed to identify a low energy conformer. The calculated properties and the ability of the compounds to inhibit the enzyme aldose reductase were correlated using regression analyses. It was found that the inhibition is favored from rigid molecules, molecules for which the conformations have a significant difference in their energy. It was also found that the inhibition influenced positively from high values of EHOMO and maximum electrostatic potential. These results could contribute to the development of overall more active compounds.

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Synthesis and Reactions of Oxazolones from L‐Tryptophan and α‐Haloacetic Anhydrides

Bergman

Lidgren

Gogoll

1992

Bulletin des Soc Chimique

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Optically active 5(4/f)-oxazoloncs havc bccn synthcsizcd from L-tryptophan and an cxccss of trifluoro-, Lrichloro-, and dicliloroacctic anhydrides. Some of thc 5(4/f)-oxazolones havc bccn furlhcr uansfonncd to thc isomeric fi(Z/~-oxazoloncs as wcll as oxazoloncs wilh cxocyclic doublc bonds. Trcalmcnt of lhc various oxazoloncs undcr hydrolytic, acidic and Fricdcl-CralLs acylation conditions gavc indole-3-pyruvic acid, a,P-dchydrotrypiophans, j3-carbolincs as wcll as thc functionalizcd cyclopcntanoindolc 32. Trcatmcnt ol the 4-(3-indolylmclhyl)-2-Lrinuoromcdlyl-5(Z//)-ox~olonc (17) with uifluoroacctic acid gavc Ui c 3,4-bridgcd azcpinoindolc 35.Introduction:

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Indoles. I. Syntheses of 1-Acetyltryptophan and Its Derivatives, and Their Friedel-Crafts Reaction

Cited by 12 publications

References 0 publications

Facile entry into the thiazolo[3,2-a]indol-3(2H)-one system via an unusual reaction with thionyl chloride

Facile entry into the thiazolo[3,2-a]indol-3(2H)-one system via an unusual reaction with thionyl chloride

Synthesis and Reactions of Oxazolones from L‐Tryptophan and α‐Haloacetic Anhydrides

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