Reaktion #1016051

ord-ae8dd6821be14cf8bfebc5f3f6061984

Reaktionsgleichung

O=C(Cc1ccccc1)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O.O=c1ccn([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]2O)c(=O)[nH]1
UDP N-phenylacetylglucosamine
CC(=O)OCC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O.O=c1ccn([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]2O)c(=O)[nH]1
UDP N-acetoxyacetylglucosamine
O=c1ccn([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]2O)c(=O)[nH]1.[N-]=[N+]=NCC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O
UDP N-azidoacetylglucosamine
O=C(Cc1ccc(-c2ccccc2)cc1)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O.O=c1ccn([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]2O)c(=O)[nH]1
UDP N-(1,1′-biphenyl-4-yl)acetylglucosamine
O=c1ccn([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]2O)c(=O)[nH]1.OC[C@H]1OC(O)[C@H](N(c2ccccc2)c2ccccc2)[C@@H](O)[C@@H]1O
UDP GlcNPh2
CC(=O)N[C@H]1[C@@H](OP(=O)(O)OP(=O)(O)OC[C@H]2O[C@@H](n3ccc(=O)[nH]c3=O)[C@H](O)[C@@H]2O)O[C@H](CO)[C@@H](O)[C@@H]1O
UDP-GlcNAc
C[O-].[Na+]
NaOMe
→
O=C(CO)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O.O=c1ccn([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]2O)c(=O)[nH]1
UDP N-hydroxyacetylglucosamine
Ausbeute 98.0%

Edukte

O=C(Cc1ccccc1)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O.O=c1ccn([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]2O)c(=O)[nH]1
UDP N-phenylacetylglucosamine
CC(=O)OCC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O.O=c1ccn([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]2O)c(=O)[nH]1
UDP N-acetoxyacetylglucosamine
O=c1ccn([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]2O)c(=O)[nH]1.[N-]=[N+]=NCC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O
UDP N-azidoacetylglucosamine
O=C(Cc1ccc(-c2ccccc2)cc1)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O.O=c1ccn([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]2O)c(=O)[nH]1
UDP N-(1,1′-biphenyl-4-yl)acetylglucosamine
O=c1ccn([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]2O)c(=O)[nH]1.OC[C@H]1OC(O)[C@H](N(c2ccccc2)c2ccccc2)[C@@H](O)[C@@H]1O
UDP GlcNPh2
CC(=O)N[C@H]1[C@@H](OP(=O)(O)OP(=O)(O)OC[C@H]2O[C@@H](n3ccc(=O)[nH]c3=O)[C@H](O)[C@@H]2O)O[C@H](CO)[C@@H](O)[C@@H]1O
UDP-GlcNAc
C[O-].[Na+]
NaOMe

Reagenzien

Keine

Lösungsmittel

CO
MeOH
—
acyl chlorides

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    SonstigeF5-8) in 68-95% yields

Vorschrift

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.

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US09290530B2uspto-grants-2016_03