An atom economic synthesis and antitubercular evaluation of novel spiro-cyclohexanones.
The 1,3-dipolar cycloaddition of azomethine ylides derived from acenaphthenequinone and alpha-amino acids viz. sarcosine, phenylglycine, 1,3-thiazolane-4-carboxylic acid and proline to a series of 2,6-bis[(E)-arylmethylidene]cyclohexanones afforded novel spiro-heterocycles chemo-, regio- and stereoselectively in quantitative yields. These compounds were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB) using agar dilution method. Two compounds, 4-(2,4-dichlorophenyl)-5-phenylpyrrolo(spiro[2.2'']acenaphthene-1''-one)spiro[3.2']-6'-(2,4-dichlorophenylmethylidene)cyclohexanone (4i) and spiro[5.2'']acenaphthene-1''-onespiro[6.2']-6'-(2,4-dichlorophenylmethylidene)cyclohexanone-7-(2,4-dichlorophenyl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole (5i) display maximum activity in vitro with a MIC value of 0.40microg/mL against MTB and were 4 and 15.6 times more potent than ethambutol and pyrazinamide, respectively.
Ranjith Kumar
Raju
R
Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625 021, Tamil Nadu, India.
Perumal
Subbu
S
Manju
S C
SC
Bhatt
Pritesh
P
Yogeeswari
Perumal
P
Sriram
Dharmarajan
D
D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D003512:Cyclohexanones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism
C542858:4-(2,4-dichlorophenyl)-5-phenylpyrrolo(spiro(2.2'')acenaphthene-1''-one)spiro(3.2')-6'-(2,4-dichlorophenylmethylidene)cyclohexanone; D000995:Antitubercular Agents; D003512:Cyclohexanones; D013141:Spiro Compounds