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.

Graphical abstract1,3-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 full-size imageDownload 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