荞麦碱

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1-deoxynojirimycin (DNJ) (1) was isolated from the roots of Morus alba (Moraceae) as described previously (28). 1-Deoxymannojirimycin (manno-DNJ) (2) and 1-deoxy-3,4-diepi-nojirimycin (gulo-DNJ) (5) have been recently isolated from the barks of Angylocalyx pynaertii (Leguminosae). 1-Deoxy-3-epi-nojirimycin (allo-DNJ) (3) was prepared by the microbial redox reaction at C-3 of the N-benzyloxycarbonyl derivative of DNJ as described previously (29) 1-Deoxygalactonojirimycin (DGJ) (4) and 1,2-dideoxy-galactonojirimycin (6) were prepared by the chemical epimerization of the 4-OH group of 1 and fagomine, respectively, according to the literature procedure (30). α-Homonojirimycin (α-HNJ) (7), α-homomannojirimycin (α-manno-HNJ) (8), and α-homoallonojirimycin (α-allo-HNJ) (9) were isolated from the whole plant of Aglaonema treubii (Araceae) as reported previously (31). α-Homogalactonojirimycin (α-galacto-HNJ) (10) was prepared from 2,3,4,6-tetra-O-benzyl-D-galactose by way of a Wittig chain extension and a mercuricyclization according to the literature procedure (33). N-Methyl-DGJ (11) was prepared by treatment of 4 with 37% HCHO and 80% formic acid according to the reference (34), and the N-ethyl (12), N-propyl (13), N-butyl (14) and N-hydroxyethyl (15) derivatives of 4 were prepared by treatment with the appropriate alkyl bromide and triethylamine in DMF. The reaction mixture of N-alkylation was evaporated in vacuo, and the residual syrup was resolved in MeOH and applied to an Amberlyst 15 column (H+ form), washed with MeOH, eluted with 0.5 M NH4OH, and concentrated. N-Alkylated derivatives were finally purified by Dowex 1x2 (OH− form) and Amberlite CG-50 (N4+ form) chromatography with water as eluent. β-1-C-Butyl-DGJ (16) was isolated from Adenophorae Radix as described previously (35). 4-epi-isofagomine (21), isofagomine (33) and its derivatives (34-37) were chemically synthesized as described previously (40). 2,5-Dideoxy-2,5-imino-D-mannitol (DMDP, 27), 1,4-dideoxy-1,4-imino-D-arabinitol (DAB, 28) were purified from Derris malaccensis and Morus alba, respectively (29). N-butyl-DNJ (30), N-dodecyl-DNJ (31), castanospermine (29) were from commercial sources. Calystegine A3 (17), calystegine A5 (22), calystegine B1 (23), calystegine B2 (18), calystegine B3 (24), calystegine B4 (25), and calystegine C1 (26) were prepared as published method (36, 40a), N-methyl calystegine A3 (19) and N-methyl calystegine B2 (20) were chemically synthesized.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1-deoxynojirimycin (DNJ) (1) was isolated from the roots of Morus alba (Moraceae) as described previously (28). 1-Deoxymannojirimycin (manno-DNJ) (2) and 1-deoxy-3,4-diepi-nojirimycin (gulo-DNJ) (5) have been recently isolated from the barks of Angylocalyx pynaertii (Leguminosae). 1-Deoxy-3-epi-nojirimycin (allo-DNJ) (3) was prepared by the microbial redox reaction at C-3 of the N-benzyloxycarbonyl derivative of DNJ as described previously (29) 1-Deoxygalactonojirimycin (DGJ) (4) and 1,2-dideoxy-galactonojirimycin (6) were prepared by the chemical epimerization of the 4-OH group of 1 and fagomine, respectively, according to the literature procedure (30). α-Homonojirimycin (α-HNJ) (7), α-homomannojirimycin (α-manno-HNJ) (8), and α-homoallonojirimycin (α-allo-HNJ) (9) were isolated from the whole plant of Aglaonema treubii (Araceae) as reported previously (31). α-Homogalactonojirimycin (α-galacto-HNJ) (10) was prepared from 2,3,4,6-tetra-O-benzyl-D-galactose by way of a Wittig chain extension and a mercuricyclization according to the literature procedure (33). N-Methyl-DGJ (11) was prepared by treatment of 4 with 37% HCHO and 80% formic acid according to the reference (34), and the N-ethyl (12), N-propyl (13), N-butyl (14) and N-hydroxyethyl (15) derivatives of 4 were prepared by treatment with the appropriate alkyl bromide and triethylamine in DMF. The reaction mixture of N-alkylation was evaporated in vacuo, and the residual syrup was resolved in MeOH and applied to an Amberlyst 15 column (H+ form), washed with MeOH, eluted with 0.5 M NH4OH, and concentrated. N-Alkylated derivatives were finally purified by Dowex 1x2 (OH− form) and Amberlite CG-50 (N4+ form) chromatography with water as eluent. β-1-C-Butyl-DGJ (16) was isolated from Adenophorae Radix as described previously (35). 4-epi-isofagomine (21), isofagomine (33) and its derivatives (34-37) were chemically synthesized as described previously (40). 2,5-Dideoxy-2,5-imino-D-mannitol (DMDP, 27), 1,4-dideoxy-1,4-imino-D-arabinitol (DAB, 28) were purified from Derris malaccensis and Morus alba, respectively (29). N-butyl-DNJ (30), N-dodecyl-DNJ (31), castanospermine (29) were from commercial sources. Calystegine A3 (17), calystegine A5 (22), calystegine B1 (23), calystegine B2 (18), calystegine B3 (24), calystegine B4 (25), and calystegine C1 (26) were prepared as published method (36, 40a), N-methyl calystegine A3 (19) and N-methyl calystegine B2 (20) were chemically synthesized.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-O-Benzyl-N-benzyloxycarbonyl-1,5-imino-1,2,5-trideoxy-D-arabino-hexitol (25) (325 mg, 0.877 mmol) was dissolved in acetic acid (8 ml) and stirred under hydrogen at atmospheric pressure with palladium black (100 mg). After 18 hours, the solution was filtered and evaporated. Subsequent purification by flash chromatography (CMAW) and ion exchange gave 1,5-imino-1,2,5-trideoxy-D-arabino-hexitol as the hydrochloride salt (158 mg, 98%) a white crystalline solid, m.p. (methanol-ether) 173°-175° C., [α]20D +17.9° (c, 0.78 in water); νmax (KBr disc) 3370, 1615, 1390, 1055, 935 and 660 cm-1 ; 1H NMR (D2O) δ 1.58 (1H, dddd, H-2, J2,2' 14.2 Hz, J2,3 11.4 Hz, J2,1 13.6 Hz, J2,1' 4.6 Hz); 2.06 (1H, dddd, J2',1' 2.4 Hz, J2',3 4.8 Hz, J2',1 3.2 Hz); 2.90-3.01 (2H, m, H-5, H-1); 3.30 (1H, ddd, H-1', J1,1' 13.2 Hz); 3.38 (1H, dd, H-4, J3,4 9.2 Hz, J4,5 10.5 Hz); 3.57 (1H, ddd, H-3); 3.73, 3.79 (2H, 2×dd, H-6,6', J6,6' 12.7 Hz, J5,6 5.2 Hz, J5,6' 3.4 Hz). 13C NMR δ29.33 (t, C-2); 42.66 (t, C-1); 58.53 (t, C-6); 60.68 (d, C-5); 70.39, 71.24 (2×d, C-3, C-4). m/z: 148 (M+H+, 100%), 116 (10%), 72 (8%). Also characterized as free base, m.p. (acetone-water) 178°-180° C., [lit.20 180°-184° C.], [α]20D +21.0° (c 0.3 in water) [lit.20 +24.7 (c 0.4 in water)]; 1H NMR δ 1.28 (1H, dddd, H-2), 1.81 (1H, dddd, H-2'), 2.40 (1H, ddd, H-1), 2.83 (1 H, ddd, H-1'), 2.99 (1H, dd, H-4), 3.37 (1H, m, H-3), 3.46 (1H, dd, H-6), 3.68 (1H, dd, H-6'); 13C NMR δ 33.45 (t, C-2), 43.30 (t, C-1), 61.59 (d, C-5), 62.45 (t, C-6), 73.98 (2×d, C-3,4). the solution was filtered evaporated Subsequent purification by flash chromatography (CMAW) and ion exchange

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1-deoxynojirimycin (DNJ) (1) was isolated from the roots of Morus alba (Moraceae) as described previously (28). 1-Deoxymannojirimycin (manno-DNJ) (2) and 1-deoxy-3,4-diepi-nojirimycin (gulo-DNJ) (5) have been recently isolated from the barks of Angylocalyx pynaertii (Leguminosae). 1-Deoxy-3-epi-nojirimycin (allo-DNJ) (3) was prepared by the microbial redox reaction at C-3 of the N-benzyloxycarbonyl derivative of DNJ as described previously (29) 1-Deoxygalactonojirimycin (DGJ) (4) and 1,2-dideoxy-galactonojirimycin (6) were prepared by the chemical epimerization of the 4-OH group 1 and fagomine, respectively, according to the literature procedure (30). α-Homonojirimycin (α-HNJ) (7), α-homomannojirimycin (α-manno-HNJ) (8), and α-homoallonojirimycin (α-allo-HNJ) (9) were isolated from the whole plant of Aglaonema treubii (Araceae) as reported previously (31). α-Homogalactonojirimycin(α-galacto-HNJ) (10) was prepared from 2,3,4,6-tetra-O-benzyl -D-galactose by way of a Wittig chain extension and a mercuricyclization according to the literature procedure (33). N-Methyl-DGJ (11) was prepared by treatment of 4 with 37% HCHO and 80% formic acid according to the reference (34), and the N-ethyl (12), N-propyl (13), N-butyl (14) and N-hydroxyethyl (15) derivatives of 4 were prepared by treatment with the appropriate alkyl bromide and triethylamine in DMF. The reaction mixture of N-alkylation was evaporated in vacuo, and the residual syrup was resolved in MeOH and applied to an Amberlyst 15 column (H+ form), washed with MeOH, eluted with 0.5 M NH4OH, and concentrated. N-Alkylated derivatives were finally purified by Dowex 1×2 (OH form) and Amberlite CG-50 (NH4+ form) chromatography with as eluent. β-1-C-Butyl-DGJ (16) was isolated from Adenophorae Radix as described previously (35). 4-epi-isofagomine (21), isofagomine (33) and its derivatives (34-37) were chemically synthesized as described previously (40). 2,5-Dideoxy-2,5-imino-D-mannitol (DMDP, 27), 1,4-dideoxy-1,4-imino-D-arabinitol (DAB, 28) were purified from Dermis malaccensis and Morus alba, respectively (29). N-butyl-DNJ (30), N-dodecyl-DNJ (31), castanospermine (29) were from commercial sources. Calystegine A3 (17), calystegine A5 (22), calystegine B1 (23), calystegine B2 (18), calystegine B3 (24), calystegine B4 (25), and calystegine C1 (26) were prepared as published method (36, 40a), N-methyl calystegine A3 (19) and N-methyl calystegine B2 (20) were chemically synthesized. Structural characterization of some inhibitors The structural characterization of the inhibitors is determined by mass spectrometry and 13C-NMR, and some of the results are presented below.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1-deoxynojirimycin (DNJ) (1) was isolated from the roots of Morus alba (Moraceae) as described previously (28). 1-Deoxymannojirimycin (manno-DNJ) (2) and 1-deoxy-3,4-diepi-nojirimycin (gulo-DNJ) (5) have been recently isolated from the barks of Angylocalyx pynaertii (Leguminosae). 1-Deoxy-3-epi-nojirimycin (allo-DNJ) (3) was prepared by the microbial redox reaction at C-3 of the N-benzyloxycarbonyl derivative of DNJ as described previously (29) 1-Deoxygalactonojirimycin (DGJ) (4) and 1,2-dideoxy-galactonojirimycin (6) were prepared by the chemical epimerization of the 4-OH group of 1 and fagomine, respectively, according to the literature procedure (30). α-Homonojirimycin (α-HNJ) (7), α-homomannojirimycin (α-manno-HNJ) (8), and α-homoallonojirimycin (α-allo-HNJ) (9) were isolated from the whole plant of Aglaonema treubii (Araceae) as reported previously (31). α-Homogalactonojirimycin (α-galacto-HNJ) (10) was prepared from 2,3,4,6-tetra-O-benzyl-D-galactose by way of a Wittig chain extension and a mercuricyclization according to the literature procedure (33). N-Methyl-DGJ (11) was prepared by treatment of 4 with 37% HCHO and 80% formic acid according to the reference (34), and the N-ethyl (12), N-propyl (13), N-butyl (14) and N-hydroxyethyl (15) derivatives of 4 were prepared by treatment with the appropriate alkyl bromide and triethylamine in DMF. The reaction mixture of N-alkylation was evaporated in vacuo, and the residual syrup was resolved in MeOH and applied to an Amberlyst 15 column (H+ form), washed with MeOH, eluted with 0.5 M NH4OH, and concentrated. N-Alkylated derivatives were finally purified by Dowex 1x2 (OH− form) and Amberlite CG-50 (N4+ form) chromatography with water as eluent. β-1-C-Butyl-DGJ (16) was isolated from Adenophorae Radix as described previously (35). 4-epi-isofagomine (21), isofagomine (33) and its derivatives (34-37) were chemically synthesized as described previously (40). 2,5-Dideoxy-2,5-imino-D-mannitol (DMDP, 27), 1,4-dideoxy-1,4-imino-D-arabinitol (DAB, 28) were purified from Derris malaccensis and Morus alba, respectively (29). N-butyl-DNJ (30), N-dodecyl-DNJ (31), castanospermine (29) were from commercial sources. Calystegine A3 (17), calystegine A5 (22), calystegine B1 (23), calystegine B2 (18), calystegine B3 (24), calystegine B4 (25), and calystegine C1 (26) were prepared as published method (36, 40a), N-methyl calystegine A3 (19) and N-methyl calystegine B2 (20) were chemically synthesized.