Uridine-Diphosphate-N-Acetylglucosamine → UDP N-hydroxyacetylglucosamine

HRID 928869

Reaktionsgleichung

Reaktionsgleichung von HRID 928869
[CH3:1][C:2]([NH:4][C@H:5]1[C@@H:10]([O:11][P:12]([O:15][P:16]([O:19][CH2:20][C@H:21]2[O:25][C@@H:24]([N:26]3[C:32](=[O:33])[NH:31][C:29](=[O:30])[CH:28]=[CH:27]3)[C@H:23]([OH:34])[C@@H:22]2[OH:35])([OH:18])=[O:17])([OH:14])=[O:13])[O:9][C@H:8]([CH2:36][OH:37])[C@@H:7]([OH:38])[C@@H:6]1[OH:39])=[O:3].C1C(=O)NC(=[O:44])N([C@@H]2O[C@H](COP(OP(O)(O)=O)(O)=O)[C@@H](O)[C@H]2O)C=1.C(OCC(N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)OC1O)=O)(=O)C.C1C(=O)NC(=O)N([C@@H]2O[C@H](COP(OP(O)(O)=O)(O)=O)[C@@H](O)[C@H]2O)C=1.N(CC(N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)OC1O)=O)=[N+]=[N-].C1C(=O)NC(=O)N([C@@H]2O[C@H](COP(OP(O)(O)=O)(O)=O)[C@@H](O)[C@H]2O)C=1.C1(CC(N[C@@H]2[C@@H](O)[C@H](O)[C@@H](CO)OC2O)=O)C=CC=CC=1.C1C(=O)NC(=O)N([C@@H]2O[C@H](COP(OP(O)(O)=O)(O)=O)[C@@H](O)[C@H]2O)C=1.C1(C2C=CC=CC=2)C=CC(CC(N[C@@H]2[C@@H](O)[C@H](O)[C@@H](CO)OC2O)=O)=CC=1.C1C(=O)NC(=O)N([C@@H]2O[C@H](COP(OP(O)(O)=O)(O)=O)[C@@H](O)[C@H]2O)C=1.OC1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1N(C1C=CC=CC=1)C1C=CC=CC=1.C[O-].[Na+]>CO>[CH:28]1[C:29](=[O:30])[NH:31][C:32](=[O:33])[N:26]([C@@H:24]2[O:25][C@H:21]([CH2:20][O:19][P:16]([O:15][P:12]([OH:13])([OH:14])=[O:11])([OH:18])=[O:17])[C@@H:22]([OH:35])[C@H:23]2[OH:34])[CH:27]=1.[OH:44][CH2:1][C:2]([NH:4][C@@H:5]1[C@@H:6]([OH:39])[C@H:7]([OH:38])[C@@H:8]([CH2:36][OH:37])[O:9][CH:10]1[OH:11])=[O:3]

Komponenten

9

Edukt 7

HCID 445675Uridine-Diphosphate-N-AcetylglucosamineHCID 10942334Sodium MethoxideHCID 131735071UDP N-acetoxyacetylglucosamineHCID 131735073UDP N-azidoacetylglucosamineHCID 131735074HCID 131735074, VerbindungHCID 131735076UDP N-(1,1'-biphenyl-4-yl)acetylglucosamineHCID 131735078UDP GlcNPh2

Produkt 1

HCID 131735070UDP N-hydroxyacetylglucosamineAusbeute 98 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

The N-TFA group in UDP-GlcNTFA (T5b-10) as well as the N3 group in UDP-GlcN3 (T5b-11) UDP-GlcNAc6N3 (T5b-12), and UDP-GlcN36S (T5b-15) can be easily converted to a free amine, allowing further modifications to generate a diverse array of N-substituted UDP-GlcNAc derivatives. As shown in FIG. 5A, the N-TFA group at C2 of UDP-GlcNTFA T5b-10 (or F5-1) was removed under mild basic condition to produce UDP-glucosamine (UDP-GlcNH2, F5-2) in 98% yield. Selective acylation of the free amine group in F5-2 using various acyl chlorides produced C-2 modified UDP-GlcNAc derivatives UDP-N-acetoxyacetylglucosamine (UDP-GlcNGcAc, F5-4), UDP-N-azidoacetylglucosamine (UDP-GlcNAz, F5-6), UDP-N-phenylacetylglucosamine (UDP-GlcNPh, F5-7), and UDP-N-(1,1′-biphenyl-4-yl)acetylglucosamine (UDP-GlcNPh2, F5-8) in 68-95% yields. Deacetylation of compound F5-4 using catalytic amount of NaOMe in MeOH provided UDP-N-hydroxyacetylglucosamine (UDP-GlcNGc, F5-5) in 98% yield. In addition, although UDP-GlcNS T5b-16 (or F5-3) was unable to be prepared from GlcNS (T5b-8) (Table 5b) in the one-pot three-enzyme system, it was readily obtained by N-sulfation of compound F5-2 with Py.SO3 in 2 M of NaOH aqueous solution in a very good yield (86%) (FIG. 5A). Similarly as shown in FIG. 5B, catalytic hydrogenation of the azido group at the C-6 of UDP-GlcNAc6N3 T5b-12 (or F5-9) generated UDP-6-amino-6-deoxyl-N-acetylglucosamine (UDP-GlcNAc6NH2, F5-10) with an excellent yield (96%). Selective acylation of the free amino group of F5-10 using various acyl chlorides produced C-6 modified UDP-GlcNAc derivatives including UDP-6-acetoxyacetamido-N-acetylglucosamine (UDP-GlcNAc6NGcAc, F5-11), UDP-6-azidoacetamido-N-acetylglucosamine (UDP-GlcNAc6NAz, F5-13), UDP-6-phenylacetamido-N-acetylglucosamine (UDP-GlcNAc6NPh, F5-14), and UDP-N-(1,1′-biphenyl-4-yl)acetamido-N-acetylglucosamine (UDP-GlcNAc6NPh2, F5-15) in 61-91% yields. Finally, C-6 modified derivative UDP-N-hydroxyacetamido-N-acetylglucosamine (UDP-GlcNAc6NGc, F5-12) was obtained in 98% yield by treating compound F5-11 in NaOMe and methanol.

Aufarbeitung

  1. customF5-8) in 68-95% yields

Quellen und Nachweise

ORD-Eintrag
ord-ae8dd6821be14cf8bfebc5f3f6061984
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09290530B2

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