Novel glycine like amino acids from glyco-α-aminonitriles as building blocks for peptide synthesis

Our interest in the glycoaminocyanation reaction led us to apply this methodology to introduce amino acids on a monosaccharide using the N-terminal position. The GAAs described in this paper are characterized by having the amino and carboxylic acid functionalities on a disubstituted position of the saccharide backbone leading to α,α-disubstituted glycines. These new sugar amino acids showed a restricted conformation involving a spontaneous intramolecular cyclization between the C- and N-terminal positions during hydrolysis or hydrogenolysis to give the corresponding oxopiperazine. Tripeptide mimics were obtained by the introduction of an additional amino acid using one-pot conditions starting from these cyclic by-products under basic media. We demonstrated that these pseudo tripeptides are good candidates for extension of the peptidic scaffold and cyclization.

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3-C-Cyano-3-deoxy-1,2:5,6-di-O-isopropylidene-3-[[(methoxycarbonyl)methyl]amino]-α-d-allofuranoseC16H24N2O7[α]D25=+30.8 (c 1.20, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R)

3-C-Cyano-3-deoxy-1,2:5,6-di-O-isopropylidene-3-[[(S)-1-(methoxycarbonyl)ethyl]amino]-α-d-allofuranoseC17H26N2O7[α]D25=+8.8 (c 1.09, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R,S)

3-C-Cyano-3-deoxy-1,2:5,6-di-O-isopropylidene-3-[[(S)-1-(methoxycarbonyl)-3-methyl butyl]amino]-α-d-allofuranoseC20H32N2O7[α]D20=-2.0 (c 1.00, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R,S)

3-C-Cyano-3-deoxy-1,2:5,6-di-O-isopropylidene-3-[[(S)-1-(methoxycarbonyl)-3-methyl thio-propyl]amino]-α-d-allofuranoseC19H30N2O7S[α]D20=+8.0 (c 1.60, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R,S)

3-C-Cyano-3-deoxy-1,2:5,6-di-O-isopropylidene-3-[[(S)-(1,3)-di-(methoxycarbonyl)propyl]amino]-α-d-allofuranoseC20H30N2O9[α]D20=+22.0 (c 1.55, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R,S)

3-C-Cyano-3-deoxy-1,2:5,6-di-O-isopropylidene-3-[[(S)-1-(methoxycarbonyl)-2-phenylethyl]amino]-α-d-allofuranoseC23H30N2O7[α]D20=+16 (c 0.21, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R,S)

3-C-Cyano-3-deoxy-1,2:5,6-di-O-isopropylidene-3-[[(tert-butoxycarbonyl)methyl]amino]-α-d-allofuranoseC19H30N2O7[α]D28=+18.7 (c 0.33, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R)

5-O-Benzyl-3-C-cyano-3-deoxy-1,2-O-isopropylidene-3-[[(methoxycarbonyl)methyl]amino]-α-d-ribofuranoseC19H24N2O6[α]D29+29.6 (c 0.63, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R)

5-O-Benzyl-3-C-cyano-3-deoxy-1,2-O-isopropylidene-3-[[(S)-1-(methoxycarbonyl)-3-methylbutyl]amino]-α-d-ribofuranoseC23H32N2O6[α]D20=-11.0 (c 1.80, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,S)

3-C-Cyano-3-deoxy-1,2-O-isopropylidene-3-[[(methoxycarbonyl)methyl]amino]-5-O-trityl-α-d-ribofuranoseC31H32N2O6[α]D25=+20.6 (c 1.00, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R)

3-C-Cyano-3-deoxy-1,2-O-isopropylidene-3-[[(S)-1-(methoxycarbonyl)ethyl]amino]-5-O-trityl-α-d-ribofuranoseC32H34N2O6[α]D25=-24.9 (c 1.18, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,S)

3-C-Cyano-3-deoxy-1,2-O-isopropylidene-3-[[(S)-1-(methoxycarbonyl)-2-phenylethyl] amino]-5-O-trityl-α-d-ribofuranoseC38H38N2O6[α]D20=+32.0 (c 0.21, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,S)

3-C-Cyano-3-deoxy-1,2:5,6-di-O-isopropylidene-3-[[(R)-1-(methoxycarbonyl)ethyl]amino]-α-d-allofuranoseC17H26N2O7[α]D20=+30 (c 0.26, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R,R)

3-C-Cyano-3-deoxy-1,2:5,6-di-O-isopropylidene-3-[[(R)-1-(methoxycarbonyl)-2-phenylethyl]amino]-α-d-allofuranoseC23H30N2O7[α]D20=-36.6 (c 0.50, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R,R)

3-C-Cyano-3-deoxy-1,2-O-isopropylidene-3-[[(R)-1-(methoxycarbonyl)ethyl]amino]-5-O-trityl-α-d-ribofuranoseC32H34N2O6[α]D20=+36.2 (c 0.50, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,R)

3-C-Cyano-3-deoxy-1,2-O-isopropylidene-3-[[(R)-1-(methoxycarbonyl)-2-phenylethyl]amino]-5-O-trityl-α-d-ribofuranoseC38H38N2O6[α]D20=-22.0 (c 0.17, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,R)

(3R)-1,2:5,6-Di-O-isopropylidenespiro[3-deoxy-α-d-ribo-hexofuranose-3,5′-piperazine]-2′-oneC15H24N2O6[α]D25=+67.8 (c 1.19, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R)

(3R,3′S)-1,2:5,6-Di-O-isopropylidene-3′-methylspiro[3-deoxy-α-d-ribo-hexofuranose-3,5′-piperazine]-2′-oneC16H26N2O6[α]D25+23.3 (c 0.54, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R,S)

(3R,3′S)-3′-Isobutyl-1,2:5,6-di-O-isopropylidenespiro[3-deoxy-α-d-ribo-hexofuranose-3,5′-piperazine]-2′-oneC19H32N2O6[α]D20=-13.0(c 1.80, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R,S)

(3R,3′S)-1,2:5,6-Di-O-isopropylidene-3′-(2-methylthioethyl)spiro[3-desoxy-α-d-ribo-hexofuranose-3,5′-piperazine]-2′-oneC18H31N2O6S[α]D20=-20.0 (c 1.40, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R,S)

(3R,3′S)-1,2:5,6-Di-O-isopropylidene-3′-[2-(methoxycarbonyl)ethyl]spiro[3-deoxy-α-d-ribo-hexofuranose-3,5′-piperazine]-2′-oneC19H30N2O8[α]D20=+11 (c 0.17, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R,S)

(3R,3′S)-3′-Benzyl-1,2:5,6-di-O-isopropylidenespiro[3-deoxy-α-d-ribo-hexofuranose-3,5′-piperazine]-2′-oneC21H28N2O6[α]D20=+18.0 (c 0.32, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R,S)

(3R)-5-O-Benzyl-1,2-O-isopropylidenespiro[3-deoxy-α-d-erythro-pentofuranose-3,5′-piperazine]-2′-oneC18H24N2O5[α]D29=+71.6 (c 0.38, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R)

(3R,3′S)-5-O-Benzyl-3′-isobutyl-1,2-O-isopropylidenespiro[3-deoxy-α-d-erythro-pentofuranose-3,5′-piperazine]-2′-oneC22H32N2O5[α]D20=+13.0 (c 0.85, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,S)

(3R)-1,2-O-Isopropylidene-5-O-trityl-spiro[3-deoxy-α-d-erythro-pentofuranose-3,5′-piperazine]-2′-oneC30H32N2O5[α]D27=+51.1 (c 0.28, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R)

(3R,3′S)-1,2-O-Isopropylidene-3′-methyl-5-O-trityl-spiro[3-deoxy-α-d-erythro-pentofuranose-3,5′-piperazine]-2′-oneC31H34N2O5[α]D27=+10.6 (c 0.39, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,S)

3-C-Cyano-3-deoxy-1,2:5,6-di-O-isopropylidene-3-[[[[(methoxycarbonyl)methyl]carbamoyl]methyl]amino]-α-d-allofuranoseC18H27N3O8[α]D28=+1.4 (c 0.38, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R)

3-Deoxy-1,2:5,6-di-O-isopropylidene-3-[[(methoxycarbonyl)methyl]amino]-3-C-[(tert-butoxycarbonyl)aminomethyl]-α-d-allofuranoseC21H37N2O9[α]D32=+13.3 (c 1.38, CHCl3)Source of chirality: chemical reactionAbsolute configuration:(1R,2R,3R,4R,5R)

3-C-(Acetamidomethyl)-3-deoxy-1,2:5,6-di-O-isopropylidene-3-[[(methoxycarbonyl)methyl]amino]-α-d-allofuranoseC18H30N2O8[α]D20=+47 (c 0.16, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R)

3-C-[[[(Benzyloxy)carbonyl]glycyl]aminomethyl]-3-deoxy-1,2:5,6-di-O-isopropylidene-3-[[(methoxycarbonyl)methyl]amino]-α-d-allofuranoseC26H37N3O10[α]D31=-1.7 (c 0.92, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R)

3-[(Carboxymethyl)amino]-3-C-cyano-3-deoxy-1,2:5,6-di-O-isopropylidene-α-d-allofuranoseC15H22N2O7[α]D29=+26.8 (c 0.47, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R)

3-C-[[[(Benzyloxy)carbonyl]glycyl]aminomethyl]-3-[(carboxymethyl)amino]-3-deoxy-1,2:5,6-di-O-isopropylidene-α-d-allofuranoseC25H35N3O10[α]D20=+18 (c 0.12, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R)

3-C-[[[(Benzyloxy)carbonyl]-l-alanyl]aminomethyl]-3-[(carboxymethyl)amino]-3-deoxy-1,2:5,6-di-O-isopropylidene-α-d-allofuranoseC26H37N3O10[α]D20=+20 (c 0.11, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R,S)

3-C-[[[(Benzyloxy)carbonyl]-l-isoleucyl]aminomethyl]-3-[(carboxymethyl)amino]-3-deoxy-1,2:5,6-di-O-isopropylidene-α-d-allofuranoseC29H43N3O10[α]D20=+27 (c 0.15, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R,S)

3-C-[[[(Benzyloxy)carbonyl]-l-phenylalanyl]aminomethyl]-3-[(carboxymethyl)amino]-3-deoxy-1,2:5,6-di-O-isopropylidene-α-d-allofuranoseC32H41N3O10[α]D20=+21 (c 0.12, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R,S)

3-C-[[[(Benzyloxy)carbonyl]glycyl]aminomethyl]-3-deoxy-1,2:5,6-di-O-isopropylidene-3-[[[[(1S)-(methoxycarbonyl)ethyl]amino]carboxy]methylamino]-α-d-allofuranoseC29H42N4O11[α]D20=+7.0 (c 0.10, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R,S)

[1S,3R,4R,5S,10S]-1-[(4R)(2,2-Dimethyl-[1,3]dioxolan-4-yl)]-3,4-O-isopropylidene-10-methyl-2-oxa-6,9,12,15-tetraaza-spiro[4.11]hexadecane- 8,11,14-trioneC20H32N4O8[α]D20=-13.0 (c 0.15, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (1R,2R,3R,4R,5R,S)

3-C-[[[(Benzyloxy)carbonyl]glycyl]aminomethyl]-3-deoxy-3-[[[[1-(methoxycarbonyl)ethyl]amino]carboxymethyl]amino]-α-d-allopyranoseC23H34N4O11[α]D20=+21 (c 0.10, H2O)Source of chirality: chemical reactionAbsolute configuration: (2R,3R,4R,5R,S)

3-Deoxy-3-[[[[1-(carboxy)ethyl]amino]carboxymethyl]amino]-3-C-[[[glycyl]amino]methyl]-α-d-allopyranose. TrifluoroactetateC14H27N4O9[α]D20=+29 (c 0.25, H2O)Source of chirality: chemical reactionAbsolute configuration: (2R,3R,4R,5R,S)

[(1R,2R,4S,5S,11S)]-1,2,5-Trihydroxy-4-hydroxymethyl-11-methyl-3-oxa-7,10,13,16-tetraaza-spiro[5.11]heptadecane-9,12,15-trioneC14H24N4O8[α]D20=+76 (c 0.10, H2O)Source of chirality: chemical reactionAbsolute configuration: (2R,3R,4R,5R,S)