Synthesis of Potential Hypnotics.

Synthetic Applications and Mechanistic Studies of the Hydroxide-Mediated Cleavage of Carbon–Carbon Bonds in Ketones

“…Purification by flash chromatography (heptane/EtOAc 95/5) gave 950 mg (88%) of the product as a colorless oil. 1 2-Ethyl-2-phenylcyclohexanone (Table 2, Entry 5): 27 Prepared in 81% yield (940 mg) as a colorless oil from 2-phenylcyclohexanone and ethyl iodide as described above for 2-methyl-2-phenylcyclohexanone. 1 H NMR (400 MHz, CDCl 3 ) δ 7.34 (t, J = 7.6 Hz, 2H), 7.23 (t, J = 7.3 Hz, 1H), 7.15 (d, J = 7.3 Hz, 2H), 2.74−2.70 (m, 1H), 2.40−2.10 (m, 2H), 1.94 (ddd, J = 2.9, 5.9, 12.0 Hz, 1H), 1.88−1.59 (m, 6H), 0.61 (t, J = 7.5 Hz, 3H).…”

Hydroxynitrile lyase-catalyzed addition of HCN to 2-substituted cyclopentanones

“…Unless otherwise stated, 1 H and 13 C NMR spectra were recorded on a Bruker AC 250 F (250 MHz) and ARX 500 (500 MHz) in CDCl 3 with TMS as the internal standard. 13 Cyclopentanones 1b-e, 15 and 4c-f 16,17 were prepared according to literature procedures. Ketones 1a, 4a, and 4b are commercially available.…”

Cycloalkanoindoles. 1. Syntheses and antiinflammatory actions of some acidic tetrahydrocarbazoles, cyclopentindoles, and cycloheptindoles

“…Pharmacology and Structure-Activity Relationships. The 15 cycloalkanoindole-1 -acetic acids [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] shown in Table I were tested orally for antiinflammatory activity in groups of six rats with established adjuvant arthritis ("therapeutic test") as described previously.7,8'14 Treatment with compounds was started 14 days after adjuvant (Mycobacterium butyricum in mineral oil) injection in the foot pad of the left hind paw and continued until day 22 (nine po administrations). A decrease of the volume of the injected paw, of 0.5 ml (approximately 50% of the maximum possible decrease) or more, as a result of drug treatment was considered to be a "therapeutic effect".…”

“…The results show that with compounds containing the 1,2,3,4-tetrahydrocarbazole-l-acetic acid grouping (24)(25)(26)(27)(28)(29)(30)(31)(32), the presence of an alkyl substituent at position 1 is essential for activity and that the optimal 1-substituent is an ethyl group. Thus, the 1-unsubstituted derivative 24, as well as the 1-methyl analogue 25, is devoid of activity at the 100 mg/kg dose, while the 1-ethyl analogue 26 is more potent than phenylbutazone (41), having an ED50 of 3.3 mg/kg.…”

“…We have shown recently9 that the introduction of an ethyl group at the 8 position of 1-ethyl-l,3,4,9-tetrahydropyrano [3,[4][5][6]indole-l-acetic acid, to generate etodolic acid (3), results in a tenfold increase in antiinflammatory activity, and this finding has been the stimulus for the synthesis and testing of 28-31, which are 8-alkyl derivatives of 1-ethyl-l,2,3,4-tetrahydrocarbazole-l-acetic acid (26). show a high level of activity with the 8-ethyl and 8-n-propyl analogues 28 and 29 being the most potent having EDso's of 1.9 and 1.1 mg/kg, respectively.…”