Uridine-Diphosphate-N-Acetylglucosamine → UDP-glucosamine

HRID 928868

Reaktionsgleichung

Reaktionsgleichung von HRID 928868
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](CON=[N+]=[N-])[C@@H](O)[C@H](O)[C@H]1NC(C)=O.CC([NH:47][C@H:48]1[C@@H:53]([O:54][P:55]([O:58][P:59]([O:62][CH2:63][C@H:64]2[O:68][C@@H:67]([N:69]3[C:75](=[O:76])[NH:74][C:72](=[O:73])[CH:71]=[CH:70]3)[C@H:66]([OH:77])[C@@H:65]2[OH:78])([OH:61])=[O:60])([OH:57])=[O:56])[O:52][C@H:51]([CH2:79][OH:80])[C@@H:50]([OH:81])[C@@H:49]1[OH:82])=O>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.FC(F)(F)C(N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)OC1O)=O.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([C@H]([C@H]([C@@H]([C@@H](CO)O)O)O)C=O)=[N+]=[N-]>[CH:71]1[C:72](=[O:73])[NH:74][C:75](=[O:76])[N:69]([C@@H:67]2[O:68][C@H:64]([CH2:63][O:62][P:59]([O:58][P:55]([O:54][C@H:53]3[O:52][C@H:51]([CH2:79][OH:80])[C@@H:50]([OH:81])[C@H:49]([OH:82])[C@H:48]3[NH2:47])([OH:57])=[O:56])([OH:61])=[O:60])[C@@H:65]([OH:78])[C@H:66]2[OH:77])[CH:70]=1

Komponenten

5

Edukt 2

HCID 445675Uridine-Diphosphate-N-AcetylglucosamineHCID 131735066UDP GlcNAc6N3

Produkt 1

HCID 167658UDP-glucosamineAusbeute 98 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 131735068HCID 131735068, VerbindungLösungsmittelHCID 131735069UDP 2-azido-2-deoxy-glucoseLösungsmittel

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. customthe N-TFA group at C2 of UDP-GlcNTFA T5b-10 (or F5-1) was removed under mild basic condition

Quellen und Nachweise

ORD-Eintrag
ord-deeaf44aa3384d5ca7ed1be1e1559aa0
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09290530B2

Verknüpfte Notizen

Wird geladen…