Asymmetric auxiliary group

• US 10,696,711 B2
• Filed: 11/06/2018
• Issued: 06/30/2020
• Est. Priority Date: 07/13/2012
• Status: Active Grant

• Current Assignee: WAVE Life Sciences Ltd.
• Original Assignee: WAVE Life Sciences Ltd.
• Inventors: Shimizu, Mamoru, Wada, Takeshi
• Primary Examiner(s): Berry, Layla D
• Application Number:
  US16/182,302
• Publication Number:
  US 20190177357A1
• Time in Patent Office: 602 Days
• Field of Search: None
• CPC Class Codes: C07B 53/00 Asymmetric syntheses
• CPC Class Codes: C07D 207/08 with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 473/18 one oxygen and one nitrogen atom, e.g. guanine
• CPC Class Codes: C07D 473/34 attached in position 6, e.g. adenine
• CPC Class Codes: C07F 7/0812 comprising a heterocyclic ring
• CPC Class Codes: C07H 1/00 Processes for the preparation of sugar derivatives
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/11 containing cyclic phosphate
• CPC Class Codes: C07H 19/207 the phosphoric or polyphosphoric acids being esterified by a further hydroxylic compound, e.g. flavine adenine dinucleotide or nicotinamide-adenine dinucleotide
• CPC Class Codes: C07H 19/213 containing cyclic phosphate
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C07H 23/00 Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12 esters with inorganic acids C07H11/00; metal salts, see parent compounds

Abstract

To provide a chiral reagent or a salt thereof.

The chiral reagent has following chemical formula (I). In the formula (I), G¹ and G² are independently a hydrogen atom, a nitro group (—NO₂), a halogen atom, a cyano group (—CN), a group of formula (II) or (III), or both G¹ and G² taken together to form a group of formula (IV).

Claims

1. An oligonucleotide on a solid support having the structure of:

2. The oligonucleotide of claim 1, wherein G³ and G⁴ are taken together to form a heteroatom-containing ring that has 3 to 16 carbon atoms.

3. The oligonucleotide of claim 1, wherein G³ and G⁴ are taken together to form a heteroatom-containing ring that has 4 carbon atoms.

4. The oligonucleotide of claim 1, wherein G′

is a hydrogen atom, a nitro group, a halogen atom, a cyano group, or a group of formula (II), (III) or (V).

5. The oligonucleotide of claim 1, wherein G² is a nitro group, a cyano group, or a group of formula (II), (III) or (V), or both G¹ and G² are taken together to form a group of formula (IV).

6. The oligonucleotide of claim 1, wherein G¹ is a hydrogen atom.

7. The oligonucleotide of claim 1, wherein each of G¹ and G² is a group of formula (II), wherein G²¹ to G²³ are independently a hydrogen atom, a nitro group, a halogen atom, a cyano group, or C_1-3 alkyl group.

8. The oligonucleotide of claim 1, wherein each of G¹ and G² is a group of formula (II), wherein each of G²¹ to G²³ is a hydrogen atom.

9. The oligonucleotide of claim 1, wherein G² is a group of formula (II), wherein G²¹ to G²³ are independently a hydrogen atom, a nitro group, a halogen atom, a cyano group or C_1-3 alkyl group.

10. The oligonucleotide of claim 1, wherein G² is a group of formula (II), wherein each of G²¹ and G²² is a hydrogen atom and G²³ is a nitro group.

11. The oligonucleotide of claim 1, wherein G² is a group of formula (III), wherein G³¹ to G³³ are independently C_1-4 alkyl group, C_6-14 aryl group, C_7-14 aralkyl group, C_1-4 alkyl C_6-14 aryl group, C_1-4 alkoxy C_6-14 aryl group, or C_6-14 aryl C_1-4 alkyl group.

12. The oligonucleotide of claim 1, wherein G² is a group of formula (III), wherein G³¹ to G³³ are independently C_1-4 alkyl group, C₆ aryl group, C_7-10 aralkyl group, C_1-4 alkyl C₆ aryl group, C_1-4 alkoxy C₆ aryl group, or C₆ aryl C_1-4 alkyl group.

13. The oligonucleotide of claim 1, wherein G² is a group of formula (III), wherein G³¹ to G³³ are independently C_1-4 alkyl group, or C₆ aryl group.

14. The oligonucleotide of claim 1, wherein G² is a group of formula (III), wherein G³¹ to G³³ are independently C_1-4 alkyl group.

15. The oligonucleotide of claim 1, wherein G² is a group of formula (III), wherein G³¹ and G³³ are C₆ aryl group and G³² is C_1-4 alkyl group.

16. The oligonucleotide of claim 1, wherein G² is a group of formula (III), wherein the C_1-4 alkyl group is a methyl group.

17. The oligonucleotide of claim 1, wherein G² is a group of formula (III), wherein G³¹ and G³³ are phenyl.

18. The oligonucleotide of claim 1, wherein G¹ and G² are taken together to form a group of formula (IV), wherein G⁴¹ to G⁴⁶ are independently a hydrogen atom, a nitro group, a halogen atom, a cyano group, or C_1-3 alkyl group.

19. The oligonucleotide of claim 1, wherein G¹ and G² are taken together to form a group of formula (IV), wherein each of G⁴¹ to G⁴⁶ is a hydrogen atom.

20. The oligonucleotide of claim 1, wherein G² is a group of formula (V), wherein each of G⁵¹ to G⁵³ are independently a hydrogen atom, a nitro group, a methyl group, or a methoxy group.

21. The oligonucleotide of claim 1, wherein G² is a group of formula (V), wherein each of G⁵¹ and G⁵³ is a hydrogen atom and G⁵³ is a 4-methyl group.

22. The oligonucleotide of claim 1, wherein a R² is hydrogen.

23. The oligonucleotide of claim 1, wherein a R² is halogen.

24. The oligonucleotide of claim 1, wherein a R² is alkyl-Y¹—

, alkenyl-Y¹—

, alkynyl-Y¹—

, aryl-Y¹—

, or heteroaryl-Y¹—

.

25. The oligonucleotide of claim 1, wherein a R² is alkyl-Y¹—

.

26. The oligonucleotide of claim 1, wherein Y¹ is O.

27. The oligonucleotide of claim 1, wherein G⁵ is trityl, 4-monomethoxytrityl, 4,4′

-dimethoxytrityl, 4,4′

,4″

-trimethoxytrityl, 9-phenylxanthin-9-yl (Pixyl) or 9-(p-methoxyphenyl)xanthin-9-yl (MOX).

28. The oligonucleotide of claim 1, wherein G⁵ is 4,4′

-dimethoxytrityl.

29. The oligonucleotide of claim 1, wherein Bs is independently an adenine, a thymine, a cytosine, a guanine, or a derivative thereof.

30. The oligonucleotide of claim 1, wherein each Bs is independently selected from:

31. The oligonucleotide of claim 30, wherein R⁸ is methyl, isopropyl, phenyl, benzyl, or phenoxymethyl.

32. The oligonucleotide of claim 30, wherein R⁹ and R¹⁰ are C_1-4 alkyl group.