ABSTRACT
Five new spiro[indoline-3,3'-indolizine]s have been synthesized with high regio- and stereospecificity in one-pot three-component reactions between a substituted indole-2,3-dione, (S)-pipecolic acid and trans-3-benzoylacrylic acid, and subsequently characterized using a combination of elemental analysis, IR and 1H and 13C NMR spectroscopy, mass spectrometry and crystal structure analysis. (1'SR,2'SR,3RS,8a'RS)-2'-Benzoyl-5-fluoro-2-oxo-1',5',6',7',8',8a'-hexahydro-2'H-spiro[indoline-3,3'-indolizine]-1'-carboxylic acid, C23H21FN2O4, (I), and (1'SR,2'SR,3RS,8a'RS)-2'-benzoyl-5-methyl-2-oxo-1',5',6',7',8',8a'-hexahydro-2'H-spiro[indoline-3,3'-indolizine]-1'-carboxylic acid, C24H24N2O4, (II), are isomorphous, as are (1'SR,2'SR,3RS,8a'RS)-2'-benzoyl-1-methyl-2-oxo-1',5',6',7',8',8a'-hexahydro-2'H-spiro[indoline-3,3'-indolizine]-1'-carboxylic acid, C24H24N2O4, (III), and (1'SR,2'SR,3RS,8a'RS)-2'-benzoyl-5-chloro-1-methyl-2-oxo-1',5',6',7',8',8a'-hexahydro-2'H-spiro[indoline-3,3'-indolizine]-1'-carboxylic acid, C24H23ClN2O4, (IV). Within each isomorphous pair, the spiro ring systems show some conformational differences. In each of (I) and (II), the molecules are linked into complex sheets by a combination of four types of hydrogen bond, and in each of (III) and (IV), a combination of O-H...O and C-H...π(arene) hydrogen bonds links the molecules to form a chain of centrosymmetric rings. In (1'SR,2'SR,3RS,8a'RS)-2'-benzoyl-1-hexyl-2-oxo-1',5',6',7',8',8a'-hexahydro-2'H-spiro[indoline-3,3'-indolizine]-1'-carboxylic acid, C29H34N2O4, (V), a combination of five hydrogen bonds links the molecules into sheets of alternating R22(16) and R66(46) rings. A mechanism is proposed for the formation of compounds (I)-(V) and some comparisons with related structures are made.
ABSTRACT
Incidence of musculoskeletal disorders (MSDs) is high among health care workers (HCWs). To determine whether MSDs are associated with preexisting anxiety and/or depression, a case-control study was carried out in female HCWs (56 cases/55 controls). Cases were HCWs with a first-time clinical diagnosis of MSD within the previous 2 years. Occupation, workplace, work shift, direct patient assistance, and anxiety/depression scores (Goldberg scale) were assessed. Increased risk of incident MSDs (multivariate logistic regression) was found in workers with preexisting anxiety/depression compared to those without (OR 5.01; 95% CI 2.20-12.05; p < .01). Other significant risk factors were direct patient assistance (OR 2.59; 95% CI 1.03-6.92; p = .04) and morning work shift (OR 2.47; 95% CI 0.99-6.48; p = .05). Preexisting anxiety/depression was associated with incident MSDs in HCWs, adjusting for occupational exposure risk factors.
