Synthesis of the ‘southern’ tripeptide of Cyclomarins A and C having novel anti-tuberculocidal mode of action

The synthesis of the ‘southern’ tripeptide of Cyclomarins A and C has been described which includes two unusual amino acids. The unusual amino acids have been synthesized and coupled with l-alanine to obtain the tripeptide.

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(S)-tert-Butyl 4-((R)-3-hydroxy-2-methylpropyl)-2,2-dimethyloxazolidine-3-carboxylateC14H27NO4[α]D23=+20.6 (c 1.0, CHCl3)Source of chirality: d-(+)-serineAbsolute configuration: (S,R)

(S)-tert-Butyl 4-((R)-3-(tert-butyldiphenylsilyloxy)-2-methylpropyl)-2,2-dimethyloxazolidine-3-carboxylateC30H45NO4Si[α]D28=+18.5 (c 1.0, CHCl3)Source of chirality: d-(+)-serineAbsolute configuration: (S,R)

tert-Butyl (2S,4R)-5-(tert-butyldiphenylsilyloxy)-1-hydroxy-4-methylpentan-2-ylcarbamateC27H41NO4Si[α]D28=-11.0 (c 1.0, CHCl3)Source of chirality: d-(+)-serineAbsolute configuration: (2S,4R)

(6R,8S)-2,2,6,12,12-Pentamethyl-10-oxo-3,3-diphenyl-4,11-dioxa-9-aza-3-silatridecane-8-carboxylic acidC27H39NO5Si[α]D30=+4.5 (c 0.64, CHCl3)Source of chirality: d-(+)-serineAbsolute configuration: (6R,8S)

(6R,8S)-2,2,6,9,12,12-Hexamethyl-10-oxo-3,3-diphenyl-4,11-dioxa-9-aza-3-silatridecane-8-carboxylic acidC28H41NO5Si[α]D28=-12.0 (c 0.5, CHCl3)Source of chirality: d-(+)-serineAbsolute configuration: (6R,8S)

(2S,3R)-Ethyl 2-amino-3-hydroxy-3-phenylpropanoateC11H15NO3[α]D20=-16.5 (c 0.52, CHCl3)Source of chirality: (S)-(−)-phenylethylamineAbsolute configuration: (2S,3R)

(2S,3R)-Ethyl 2-((S)-2-(tert-butoxycarbonylamino)propanamido)-3-hydroxy-3-phenylpropanoateC19H28N2O6[α]D28=-21.5 (c 1.0, CHCl3)Source of chirality: (S)-(−)-phenylethylamine, l-alanineAbsolute configuration: (2S,3R,S)

(2S,3R)-Ethyl 2-((S)-2-(tert-butoxycarbonylamino)propanamido)-3-methoxy-3-phenylpropanoateC20H30N2O6[α]D28=-45.0 (c 1.05, CHCl3)Source of chirality: (S)-(−)-phenylethylamine, l-alanineAbsolute configuration: (2S3R,S)

(6R,8S,11S,14S)-Ethyl 8-(tert-butoxycarbonyl(methyl)amino)-14-((R)-methoxy(phenyl)methyl)-2,2,6,11-tetramethyl-9,12-dioxo-3,3-diphenyl-4-oxa-10,13-diaza-3-silapentadecan-15-oateC43H61N3O8Si[α]D28=-32.0 (c 0.025, CHCl3)Source of chirality: d-(+)-serine, (S)-(−)-phenylethylamine, l-alanineAbsolute configuration: (6R,8S,11S,14S,14R)

(6R,8S,11S,14S)-8-(tert-Butoxycarbonyl(methyl)amino)-14-((R)-methoxy(phenyl)methyl)-2,2,6,11-tetramethyl-9,12-dioxo-3,3-diphenyl-4-oxa-10,13-diaza-3-silapentadecan-15-oic acidC41H57N3O8Si[α]D23=-16.2. (c 0.30, CHCl3)Source of chirality: d-(+)-serine, (S)-(−)-phenylethylamine, l-alanineAbsolute configuration: (6R,8S,11S,14S,14R)

(6R,8S,11S,14S)-Methyl 8-(tert-butoxycarbonyl(methyl)amino)-14-((R)-methoxy(phenyl)methyl)-2,2,6,11-tetramethyl-9,12-dioxo-3,3-diphenyl-4-oxa-10,13-diaza-3-silapentadecan-15-oateC42H59N3O8Si[α]D23=-1.85 (c 0.27, CHCl3)Source of chirality: d-(+)-serine, (S)-(−)-phenylethylamine, l-alanineAbsolute configuration: (6R,8S,11S,14S,R)