1,3-Dipolar cycloaddition of nitrile oxides to (R)-1-(1-phenylethyl)-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones: synthesis and antimycobacterial evaluation of novel enantiomerically pure di- and trispiroheterocycles

Enantiomerically pure (R)-(1-phenylethyl)-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones were synthesized for the first time, and their 1,3-dipolar cycloaddition with nitrile oxides affording di- and trispiroheterocycles regio- and stereoselectively in moderate yields was investigated. These compounds were evaluated against Mycobacterium tuberculosis H37Rv (MTB) and multi-drug-resistant M. tuberculosis (MDR-TB). Among the compounds screened, the dispiroheterocycle, namely, (5R,6R,10S)-3,9-bis(4-chlorophenyl)-10-(2,4-dichlorophenyl)-14-[(E)-(2,4-dichlorophenyl)methylidene]-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-tri-azadispiro[4.0.4.4]tetradeca-2,8-diene 5m was found to possess the maximum activity with MIC of 0.49 μM against MTB, being 9.6 and 15.6 times more potent than ciprofloxacin and ethambutol, respectively. Against MDR-TB, 5m displayed maximum activity with an MIC of 0.49 μM, with it thus being more active than rifampicin, isoniazid, ciprofloxacin and ethambutol by 7.8, 23, 77 and 124 times, respectively.

1,3-Dipolar cycloaddition of enantiomerically pure (R)-(1-phenylethyl)-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones with nitrile oxides affords di- and trispiroheterocycles regio- and stereoselectively in moderate yields and these spiroheterocycles display good anti-tubercular activities against Mycobacterium tuberculosis H37Rv (MTB) and multi-drug-resistant M. tuberculosis (MDR-TB).Figure optionsDownload as PowerPoint slide

(R)-(1-Phenylethyl)-3,5-bis[(E)-phenylmethylidene]tetrahydro-4(1H)-pyridinoneC27H25NO[α]D = +10.5 (c 0.20, CHCl3)Absolute configuration: (R)Source of chirality: (R)-1-phenylethylamine

3,5-Bis[(E)-(4-chlorophenyl)methylidene]-1-[(R)-1-phenylethyl]tetrahydro-4(1H)-pyridinoneC27H23Cl2NO[α]D = +21.0 (c 0.20, CHCl3)Absolute configuration: (R)Source of chirality: (R)-1-phenylethylamine

3,5-Bis[(E)-(4-methylphenyl)methylidene]-1-[(R)-1-phenylethyl]tetrahydro-4(1H)-pyridinoneC29H29NO[α]D = +13.0 (c 0.20, CHCl3)Absolute configuration: (R)Source of chirality: (R)-1-phenylethylamine

3,5-Bis[(E)-(2-chlorophenyl)methylidene]-1-[(R)-1-phenylethyl]tetrahydro-4(1H)-pyridinoneC27H23Cl2NO[α]D = +12.0 (c 0.20, CHCl3)Absolute configuration: (R)Source of chirality: (R)-1-phenylethylamine

3,5-Bis[(E)-(2-bromophenyl)methylidene]-1-[(R)-1-phenylethyl]tetrahydro-4(1H)-pyridinoneC27H23Br2NO[α]D = +14.0 (c 0.20, CHCl3)Absolute configuration: (R)Source of chirality: (R)-1-phenylethylamine

3,5-Bis[(E)-(2,4-dichlorophenyl)methylidene]-1-[(R)-1-phenylethyl]tetrahydro-4(1H)-pyridinoneC27H21Cl4NO[α]D = +17.0 (c 0.20, CHCl3)Absolute configuration: (R)Source of chirality: (R)-1-phenylethylamine

3,5-Bis[(E)-1-naphthylmethylidene]-1-[(R)-1-phenylethyl]tetrahydro-4(1H)-pyridinoneC35H29NO[α]D = +50.0 (c 0.20, CHCl3)Absolute configuration: (R)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-3,9,10-Triphenyl-12-[(R)-1-phenylethyl]-14-[(E)-phenylmethylidene]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H35N3O3[α]D = −102.0 (c 0.19, CHCl3)Absolute configuration: (5S,6S,10R)Source of chirality: (R)-1-phenylethylamine

(5R,6R,10S)-3,9,10-Triphenyl-12-[(R)-1-phenylethyl]-14-[(E)-phenylmethylidene]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H35N3O3[α]D = +180.0 (c 0.19, CHCl3)Absolute configuration: (5R,6R,10S)Source of chirality: (R)-1-phenylethylamine

3,4,10,11-Tetraphenyl-13-[(R)-1-phenylethyl]-1,8-dioxa-2,9,13-triazadispiro[4.1.4.3]tetradeca-2,9-dien-6-oneC41H35N3O3[α]D = −135.0 (c 0.10, CHCl3)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-3,9-Bis(4-chlorophenyl)-10-phenyl-12-[(R)-1-phenylethyl]-14-[(E)-phenylmethylidene]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H33Cl2N3O3[α]D = −154.0 (c 0.22, CHCl3)Absolute configuration: (5S,6S,10R)Source of chirality: (R)-1-phenylethylamine

(5R,6R,10S)-3,9-Bis(4-chlorophenyl)-10-phenyl-12-[(R)-1-phenylethyl]-14-[(E)-phenylmethylidene]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H33Cl2N3O3[α]D = +198.0 (c 0.16, CHCl3)Absolute configuration: (5R,6R,10S)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-10-(4-Chlorophenyl)-14-[(E)-(4-chlorophenyl)methylidene]-3,9-diphenyl-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H33Cl2N3O3[α]D = −118.0 (c 0.18, CHCl3)Absolute configuration: (5S,6S,10R)Source of chirality: (R)-1-phenylethylamine

(5R,6R,10S)-10-(4-Chlorophenyl)-14-[(E)-(4-chlorophenyl)methylidene]-3,9-diphenyl-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H33Cl2N3O3[α]D = +180.0 (c 0.19, CHCl3)Absolute configuration: (5R,6R,10S)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-3,9,10-Tris(4-chlorophenyl)-14-[(E)-(4-chlorophenyl)methylidene]-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H31Cl4N3O3[α]D = −138.0 (c 0.15, CHCl3)Absolute configuration: (5S,6S,10R)Source of chirality: (R)-1-phenylethylamine

(5R,6R,10S)-3,9,10-Tris(4-chlorophenyl)-14-[(E)-(4-chlorophenyl)methylidene]-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H31Cl4N3O3[α]D = +202.0 (c 0.18, CHCl3)Absolute configuration: (5R,6R,10S)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-10-(4-Chlorophenyl)-14-[(E)-1-(4-chlorophenyl)methylidene]-3,9-di(4-isopropylphenyl)-12-(1-phenylethyl)-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC47H45Cl2N3O3[α]D = −156.0 (c 0.21, CHCl3)Absolute configuration: (5S,6S,10R)Source of chirality: (R)-1-phenylethylamine

(5R,6R,10S)-10-(4-Chlorophenyl)-14-[(E)-1-(4-chlorophenyl)methylidene]-3,9-di(4-isopropylphenyl)-12-(1-phenylethyl)-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC47H45Cl2N3O3[α]D = +188.0 (c 0.19, CHCl3)Absolute configuration: (5R,6R,10S)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-10-(4-Methylphenyl)-14-[(E)-(4-methylphenyl)methylidene]-3,9-diphenyl-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC43H39N3O3[α]D = −160.0 (c 0.19, CHCl3)Absolute configuration: (5S,6S,10R)Source of chirality: (R)-1-phenylethylamine

(5R,6R,10S)-10-(4-Methylphenyl)-14-[(E)-(4-methylphenyl)methylidene]-3,9-diphenyl-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC43H39N3O3[α]D = +180.0 (c 0.19, CHCl3)Absolute configuration: (5R,6R,10S)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-3,9-Bis(4-chlorophenyl)-10-(4-methylphenyl)-14-[(E)-(4-methylphenyl) methylidene]-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC43H37Cl2N3O3[α]D = −103.0 (c 0.20, CHCl3)Absolute configuration: (5S,6S,10R)Source of chirality: (R)-1-phenylethylamine

(5R,6R,10S)-3,9-Bis(4-chlorophenyl)-10-(4-methylphenyl)-14-[(E)-(4-methylphenyl) methylidene]-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC43H37Cl2N3O3[α]D = +196.0 (c 0.18, CHCl3)Absolute configuration: (5R,6R,10S)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-10-(2-Chlorophenyl)-14-[(E)-(2-chlorophenyl)methylidene]-3,9-diphenyl-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H33Cl2N3O3[α]D = −142.0 (c 0.17, CHCl3)Absolute configuration: (5S,6S,10R)Source of chirality: (R)-1-phenylethylamine

(5R,6R,10S)-10-(2-Chlorophenyl)-14-[(E)-(2-chlorophenyl)methylidene]-3,9-diphenyl-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H33Cl2N3O3[α]D = +182.0 (c 0.21, CHCl3)Absolute configuration: (5R,6R,10S)Source of chirality: (R)-1-phenylethylamine

4,11-Bis(2-chlorophenyl)-3,10-diphenyl-13-[(R)-1-phenylethyl]-1,8-dioxa-2,9,13-triazadispiro[4.1.4.3]tetradeca-2,9-dien-6-oneC41H33Cl2N3O3[α]D = −122.0 (c 0.10, CHCl3)Source of chirality: (R)-1-phenylethylamine

(4R,5S,6R,11R,15S)-4,15-Bis(2-chlorophenyl)-3,9,14-triphenyl-17-[(R)-1-phenylethyl]-1,7,10,12-tetraoxa-2,8,13,17-tetraazatrispiro[4.0.4.0.4.3]octadeca-2,8,13-trieneC48H38Cl2N4O4[α]D = +24.0 (c 0.10, CHCl3)Absolute configuration: (4R,5S,6R,11R,15S)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-10-(2-Chlorophenyl)-3,9-bis(4-chlorophenyl)-14-[(E)-(2-chlorophenyl)methylidene]-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H31Cl4N3O3[α]D = −151.0 (c 0.23, CHCl3)Absolute configuration: (5S,6S,10R)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-10-(2-Chlorophenyl)-3,9-bis(4-chlorophenyl)-14-[(E)-(2-chlorophenyl)methylidene]-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H31Cl4N3O3[α]D = +186.0 (c 0.21, CHCl3)Absolute configuration: (5R,6R,10S)Source of chirality: (R)-1-phenylethylamine

(4R,5S,6R,11R,15S)-4,15-Bis(2-chlorophenyl)-3,9,14-tris(4-chlorophenyl)-17-[(R)-1-phenylethyl]-1,7,10,12-tetraoxa-2,8,13,17-tetraazatrispiro[4.0.4.0.4.3]octadeca-2,8,13-trieneC48H35Cl5N4O4[α]D = +16.0 (c 0.10, CHCl3)Absolute configuration: (4R,5S,6R,11R,15S)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-10-(2-Bromophenyl)-14-[(E)-1-(2-bromophenyl)methylidene]-3,9-diphenyl-12-(1-phenylethyl)-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H33Br2N3O3[α]D = −140.0 (c 0.18, CHCl3)Absolute configuration: (5S,6S,10R)Source of chirality: (R)-1-phenylethylamine

(5R,6R,10S)-10-(2-Bromophenyl)-14-[(E)-1-(2-bromophenyl)methylidene]-3,9-diphenyl-12-(1-phenylethyl)-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H33Br2N3O3[α]D = +186.0 (c 0.21, CHCl3)Absolute configuration: (5R,6R,10S)Source of chirality: (R)-1-phenylethylamine

(4R,5S,6R,11R,15S)-4,15-Bis (2-bromophenyl)-3,9,14-triphenyl-17-(1-phenylethyl)-1,7,10,12-tetraoxa-2,8,13,17-tetraazatrispiro[4.0.4.0.4.3]octadeca-2,8,13-trieneC48H38Br2N4O4[α]D = +14.0 (c 0.10, CHCl3)Absolute configuration: (4R,5S,6R,11R,15S)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-10-(2-Bromophenyl)-14-[(E)-1-(2-bromophenyl)methylidene]-3,9-di(4-chlorophenyl)-12-(1-phenylethyl)-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H31Br2N3O3[α]D = −120.0 (c 0.21, CHCl3)Absolute configuration: (5S,6S,10R)Source of chirality: (R)-1-phenylethylamine

(5R,6R,10S)-10-(2-Bromophenyl)-14-[(E)-1-(2-bromophenyl)methylidene]-3,9-di(4-chlorophenyl)-12-(1-phenylethyl)-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H31Br2Cl2N3O3[α]D = +196.0 (c 0.21, CHCl3)Absolute configuration: (5R,6R,10S)Source of chirality: (R)-1-phenylethylamine

4,11-Bis(2-bromophenyl)-3,10-bis(4-chlorophenyl)-13-(1-phenylethyl)-1,8-dioxa-2,9,13-triazadispiro[4.1.4.3]tetradeca-2,9-dien-6-oneC41H31Br2Cl2N3O3[α]D = −130.0 (c 0.10, CHCl3)Source of chirality: (R)-1-phenylethylamine

(4R,5S,6R,11R,15S)-4,15-Bis(2-bromophenyl)-3,9,14-tri(4-chlorophenyl)-17-(1-phenylethyl)-1,7,10,12-tetraoxa-2,8,13,17-tetraazatrispiro[4.0.4.0.4.3]octadeca-2,8,13-trieneC48H35Br2Cl2N3O3[α]D = +20.0 (c 0.10, CHCl3)Absolute configuration: (4R,5S,6R,11R,15S)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-10-(2,4-dichlorophenyl)-14-[(E)-(2,4-dichlorophenyl)methylidene]-3,9-diphenyl-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H31Cl4N3O3[α]D = −155.0 (c 0.20, CHCl3)Absolute configuration: (5S,6S,10R)Source of chirality: (R)-1-phenylethylamine

(5R,6R,10S)-10-(2,4-Dichlorophenyl)-14-[(E)-(2,4-dichlorophenyl)methylidene]-3,9-diphenyl-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]-tetradeca-2,8-dieneC41H31Cl4N3O3[α]D = +191.0 (c 0.18, CHCl3)Absolute configuration: (5R,6R,10S)Source of chirality: (R)-1-phenylethylamine

(4R,5S,6R,11R,15S)-4,15-Bis(2,4-dichlorophenyl)-3,9,14-triphenyl-17-[(R)-1-phenylethyl]-1,7,10,12-tetraoxa-2,8,13,17-tetraazatrispiro[4.0.4.0.4.3]octadeca-2,8,13-trieneC48H36Cl4N4O4[α]D = +18.0 (c 0.10, CHCl3)Absolute configuration: (4R,5S,6R,11R,15S)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-3,9-Bis(4-chlorophenyl)-10-(2,4-dichlorophenyl)-14-[(E)-(2,4-dichlorophenyl)methylidene]-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H29Cl6N3O3[α]D = −168.0 (c 0.18, CHCl3)Absolute configuration: (5S,6S,10R)Source of chirality: (R)-1-phenylethylamine

(5R,6R,10S)-3,9-Bis(4-chlorophenyl)-10-(2,4-dichlorophenyl)-14-[(E)-(2,4-dichlorophenyl)methylidene]-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC41H29Cl6N3O3[α]D = +185.5 (c 0.21, CHCl3)Absolute configuration: (5R,6R,10S)Source of chirality: (R)-1-phenylethylamine

(4R,5S,6R,11R,15S)-3,9,14-Tris(4-chlorophenyl)-4,15-bis(2,4-dichlorophenyl)-17-[(R)-1-phenylethyl]-1,7,10,12-tetraoxa-2,8,13,17-tetraazatrispiro[4.0.4.0.4.3]octadeca-2,8,13-trieneC48H33Cl7N4O4[α]D = +12.0 (c 0.10, CHCl3)Absolute configuration: (4R,5S,6R,11R,15S)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-10-(2,4-dichlorophenyl)-14-[(E)-(2,4-dichlorophenyl)methylidene]-3,9-diphenyl-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC47H43Cl4N3O3[α]D = −170.0 (c 0.19, CHCl3)Absolute configuration: (5S,6S,10R)Source of chirality: (R)-1-phenylethylamine

(5R,6R,10S)-10-(2,4-Dichlorophenyl)-14-[(E)-(2,4-dichlorophenyl)methylidene]-3,9-diphenyl-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC47H43Cl4N3O3[α]D = +190.5 (c 0.20, CHCl3)Absolute configuration: (5R,6R,10S)Source of chirality: (R)-1-phenylethylamine

(4R,5S,6R,11R,15S)-4,15-Bis(2,4-dichlorophenyl)-3,9,14-triphenyl-17-[(R)-1-phenylethyl]-1,7,10,12-tetraoxa-2,8,13,17-tetraazatrispiro[4.0.4.0.4.3]octadeca-2,8,13-trieneC57H43Cl4N3O3[α]D = +16.0 (c 0.10, CHCl3)Absolute configuration: (4R,5S,6R,11R,15S)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-10-(1-Naphthyl)-14-[(E)-1-naphthylmethylidene]-3,9-diphenyl-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC49H39N3O3[α]D = −157.5 (c 0.17, CHCl3)Absolute configuration: (5S,6S,10R)Source of chirality: (R)-1-phenylethylamine

(5R,6R,10S)-10-(1-Naphthyl)-14-[(E)-1-naphthylmethylidene]-3,9-diphenyl-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC49H39N3O3[α]D = +196.0 (c 0.19, CHCl3)Absolute configuration: (5R,6R,10S)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-3,9-Bis(4-chlorophenyl)-10-(1-naphthyl)-14-[(E)-1-naphthylmethylidene]-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC49H37Cl2N3O3[α]D = −169.5 (c 0.21, CHCl3)Absolute configuration: (5S,6S,10R)Source of chirality: (R)-1-phenylethylamine

(5R,6R,10S)-3,9-Bis(4-chlorophenyl)-10-(1-naphthyl)-14-[(E)-1-naphthylmethylidene]-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC49H37Cl2N3O3[α]D = +212.0 (c 0.19, CHCl3)Absolute configuration: (5R,6R,10S)Source of chirality: (R)-1-phenylethylamine

(5S,6S,10R)-3,9-Bis(4-isopropylphenyl)-10-(1-naphthyl)-14-[(E)-1-(1-naphthyl) methylidene]-12-(1-phenylethyl)-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC55H51N3O3[α]D = −172.0 (c 0.19, CHCl3)Absolute configuration: (5S,6S,10R)Source of chirality: (R)-1-phenylethylamine

(5R,6R,10S)-3,9-Bis(4-isopropylphenyl)-10-(1-naphthyl)-14-[(E)-1-(1-naphthyl)methylidene]-12-(1-phenylethyl)-1,4,7-trioxa-2,8,12-triazadispiro[4.0.4.4]tetradeca-2,8-dieneC55H51N3O3[α]D = +202.0 (c 0.19, CHCl3)Absolute configuration: (5R,6R,10S)Source of chirality: (R)-1-phenylethylamine