Hydrated and anhydrous polymorphs of 2′-O-fucosyllactose and their production methods
This invention describes new hydrated and anhydrous polymorphs of 2′-0-ficosyllactose (2′FL): Polymorph A 2′FL-3/2H 2 O, Polymorph B 2TL-5/2H 2 O and anhydrous Polymorph C. There is also a description of the methods for obtaining them, and of a new method for preparing Polymorph I already known in the literature.
1. 2′-O-Fucosyllactose (2′FL) in anhydrous crystalline form of polymorph C, wherein said polymorph C has characteristic XRPD peaks at 17.58±0.20, 17.44±0.20, 10.63±0.20 2Θ.
2. A polymorph C according to claim 1 , having characteristic XRPD peaks at 17.58±0.20, 17.44±0.20, 10.63±0.20, 5.30±0.2, 20.05±0.20 2Θ.
3. A polymorph C according to claim 1 , wherein the single crystal is arranged within a monocline system and the elementary cell has the following parameters: a=5.058(1) Å, b=12.773(3) Å, c=16.692(5) Å and a volume of 1074.75 Å 3 .
4. A method for preparing the polymorph C according to claim 1 , the method comprising crystallizing 2′FL from a C 1 -C 4 alcohol or mixtures thereof.
5. A method for obtaining crystalline 2′-O-Fucosyllactose (2′FL) anhydrate in form of polymorph C with molecular formula C 18 H 32 O 15 , the method comprising:
providing a mixture comprising (i) a C 1 -C 3 alcohol or mixture thereof and (ii) a 2′FL hydrate in form of polymorph A with molecular formula C 18 H 32 O 15 .nH 2 O wherein n is 3/2; and
warming the mixture at a temperature in range of 30° C. to 70° C. for 1 hr to 24 hr, thereby crystallizing the 2′FL and forming 2′FL anhydrate in form of polymorph C crystals suspended in the mixture.
6. The method of claim 5 , further comprising:
cooling the mixture; and
separating polymorph C crystals from the mixture to collect solid polymorph C crystals.
7. The method of claim 6 , comprising cooling the mixture to a temperature in a range of 10° C. to 15° C.
8. The method of claim 5 , wherein the C 1 -C 3 alcohol comprises methanol.
9. The method of claim 5 , comprising warming the mixture at a temperature in range of 60° C. to 65° C. for 1 hr to 4 hr.
10. The method of claim 5 , wherein the polymorph A has characteristic XRPD peaks at 18.86±0.20, 9.89±0.20, and 17.05±0.20 2Θ.
11. The method of claim 5 , wherein the polymorph A has characteristic XRPD peaks at 18.86±0.20, 9.89±0.20, 17.05±0.20, 21.65±0.20, and 14.20±0.20 2Θ.
12. The method of claim 5 , wherein a single crystal of the polymorph A has a P2 1 2 1 2 1 spatial group which is arranged within an orthorhombic crystalline system and the crystal comprises elementary cells having the following parameters: a=12.4098(8) Å, b=12.737(2) Å, c=13.756(2) Å and a volume of 2212.5 Å 3 .
13. The method of claim 5 , wherein the polymorph A has a β anomeric conformation.
14. The method of claim 5 , wherein the polymorph A has a predominantly β anomeric conformation with an α anomer content of less than 15%.
15. The method of claim 5 , wherein the polymorph C has characteristic XRPD peaks at 17.58±0.20, 17.44±0.20, and 10.63±0.20 2Θ.
16. The method of claim 5 , wherein the polymorph C has characteristic XRPD peaks at 17.58±0.20, 17.44±0.20, 10.63±0.20, 5.30±0.20, and 20.05±0.20 2Θ.
17. The method of claim 5 , wherein a single crystal of the polymorph C is arranged within a monocline system and the elementary cell has the following parameters: a=5.058(1) Å, b=12.773(3) Å, c=16.692(5) Å and a volume of 1074.75 Å 3 .
18. The method of claim 5 , wherein the polymorph C has a β anomeric conformation.
19. The method of claim 5 , wherein the polymorph C has a predominantly β anomeric conformation with an α anomer content of less than 15%.