Chiral auxiliaries

Patent metadata

Field	Value
Publication number	US-10428019-B2
Application number	US-201113825627-A
Country	US
Kind code	B2
Filing date	Sep 22, 2011
Priority date	Sep 24, 2010
Publication date	Oct 1, 2019
Grant date	Oct 1, 2019

Abstract

The disclosed and claimed compounds are chiral auxiliaries useful for efficiently producing a phosphorus atom-modified nucleic acid derivative with high stereoregularity. The disclosed and claimed compounds include those represented by the following formula (I) or formula (XI) for introducing the chiral auxiliaries.

First claim

What is claimed is:

1. A nucleic acid derivative comprising a chiral auxiliary, wherein the chiral auxiliary is represented by formula (II) and binds to a phosphorus atom of a phosphite moiety of the nucleic acid derivative through the oxygen atom of the chiral auxiliary, wherein the squiggly line represents the point of attachment to a phosphorus atom of a phosphite moiety of the nucleic acid derivative:

in which R 1 and R 2 independently represent a hydrogen atom, an unsubstituted or substituted alkyl group, an unsubstituted or substituted alkenyl group, an unsubstituted or substituted alkynyl group, an unsubstituted or substituted alkoxy group, an unsubstituted or substituted aralkyl group, or an unsubstituted or substituted aryl group;
R 3 represents an unsubstituted or substituted aryl group or an unsubstituted or substituted alkyl group;
R 4 and R 5 independently represent a hydrogen atom, an unsubstituted or substituted alkyl group, an unsubstituted or substituted alkenyl group, an unsubstituted or substituted alkynyl group, an unsubstituted or substituted alkoxy group, an unsubstituted or substituted aralkyl group, or an unsubstituted or substituted aryl group;
Y represents -Y 1 -Y 2 -, where Y 1 represents —C(R 6 )(R 7 )— in which R 6 and R 7 independently represent a hydrogen atom, an unsubstituted or substituted alkyl group, an unsubstituted or substituted alkenyl group, an unsubstituted or substituted alkynyl group, an unsubstituted or substituted alkoxy group, an unsubstituted or substituted aralkyl group, or an unsubstituted or substituted aryl group, or Y 1 represents an unsubstituted or substituted o-aryldiyl group, and Y 2 represents a single bond or —C(R 8 )(R 9 )— in which R 8 and R 9 independently represent a hydrogen atom, an unsubstituted or substituted alkyl group, an unsubstituted or substituted alkenyl group, an unsubstituted or substituted alkynyl group, an unsubstituted or substituted alkoxy group, an unsubstituted or substituted aralkyl group, or an unsubstituted or substituted aryl group.

2. The nucleic acid derivative of claim 1 , wherein R 3 represents an unsubstituted or substituted aryl group.

3. The nucleic acid derivative of claim 2 , wherein Y 2 represents a single bond.

4. The nucleic acid derivative of claim 1 , wherein Y 1 represents an unsubstituted or substituted o-aryldiyl group.

5. A nucleoside-3′-phosphoramidite reagent represented by formula (IV):

in which R 1 and R 2 independently represent a hydrogen atom, an unsubstituted or substituted alkyl group, an unsubstituted or substituted alkenyl group, an unsubstituted or substituted alkynyl group, an unsubstituted or substituted alkoxy group, an unsubstituted or substituted aralkyl group, or an unsubstituted or substituted aryl group;
R 3 represents an unsubstituted or substituted aryl group or an unsubstituted or substituted alkyl group;
R 4 and R 5 independently represent a hydrogen atom, an unsubstituted or substituted alkyl group, an unsubstituted or substituted alkenyl group, an unsubstituted or substituted alkynyl group, an unsubstituted or substituted alkoxy group, an unsubstituted or substituted aralkyl group, or an unsubstituted or substituted aryl group;
Y represents -Y 1 -Y 2 -, where Y 1 represents —C(R 6 )(R 7 )— in which R 6 and R 7 independently represent a hydrogen atom, an unsubstituted or substituted alkyl group, an unsubstituted or substituted alkenyl group, an unsubstituted or substituted alkynyl group, an unsubstituted or substituted alkoxy group, an unsubstituted or substituted aralkyl group, or an unsubstituted or substituted aryl group, or Y 1 represents an unsubstituted or substituted o-aryldiyl group, and Y 2 represents a single bond or —C(R 8 )(R 9 )— in which R 8 and R 9 independently represent a hydrogen atom, an unsubstituted or substituted alkyl group, an unsubstituted or substituted alkenyl group, an unsubstituted or substituted alkynyl group, an unsubstituted or substituted alkoxy group, an unsubstituted or substituted aralkyl group, or an unsubstituted or substituted aryl group;
R 21 represents a protective group of a hydroxyl group;
R 22 represents a hydrogen atom, an alkoxy group, a fluorine atom, or a protected hydroxyl group; and
Bs represents a nucleobase.

6. The reagent of claim 5 , wherein R 3 represents an unsubstituted or substituted aryl group.

7. The reagent of claim 5 , wherein Y 1 represents an unsubstituted or substituted o-aryldiyl group.

8. The reagent of claim 7 , wherein Y 2 represents a single bond.

9. A compound represented by formula (XI), or a salt thereof:

in which R 101 and R 102 independently represent a hydrogen atom, an unsubstituted or substituted alkyl group, an unsubstituted or substituted alkenyl group, an unsubstituted or substituted alkynyl group, an unsubstituted or substituted alkoxy group, an unsubstituted or substituted aralkyl group, or an unsubstituted or substituted aryl group;
R 103 represents a cyano group, a halogen atom, a halogenated unsubstituted or substituted alkyl group, a substituted or unsubstituted halogenated alkanoyl group, a C 1 -C 6 alkylsulfonyl group, a substituted or unsubstituted halogenated alkylsulfonyl group, or a nitro group;
Z represents -Z 1 -Z 2 -, in which Z 1 represents —C(R 104 )(R 105 )— wherein R 104 and R 105 independently represent a hydrogen atom, an unsubstituted or substituted alkyl group, an unsubstituted or substituted alkenyl group, an unsubstituted or substituted alkynyl group, an unsubstituted or substituted alkoxy group, an unsubstituted or substituted aralkyl group, or an unsubstituted or substituted aryl group, and Z 2 represents a single bond or —C(R 106 )(R 107 )— wherein R 106 and R 107 independently represent a hydrogen atom, an unsubstituted or substituted alkyl group, an unsubstituted or substituted alkenyl group, an unsubstituted or substituted alkynyl group, an unsubstituted or substituted alkoxy group, an unsubstituted or substituted aralkyl group, or an unsubstituted or substituted aryl group.

10. The compound or a salt thereof according to claim 9 , wherein R 101 and R 102 are independently a hydrogen atom or an unsubstituted or substituted alkyl group, R 103 is a cyano group, and Z is —C(R 104 )(R 105 )— wherein R 104 and R 105 are independently a hydrogen atom or an unsubstituted or substituted alkyl group.

11. The compound or a salt thereof of claim 9 , wherein R 101 and R 102 are hydrogen atoms, R 103 is a cyano group, and Z is —C(R 106 )(R 105 )— wherein R 104 and R 105 are hydrogen atoms.

12. The compound or a salt thereof of claim 9 , wherein R 103 is a cyano group.

13. A nucleic acid derivative, wherein a chiral auxiliary represented by the following general formula (XII) binds to a phosphorus atom of a phosphite moiety of the nucleic acid derivative through the oxygen of the chiral auxiliary, wherein the squiggly line represents the point of attachment to a phosphorus atom of a phosphite moiety of the nucleic acid derivative:

in which R 101 and R 102 independently represent a hydrogen atom, an unsubstituted or substituted alkyl group, an unsubstituted or substit

Assignees

• Wada Takeshi
• Shimizu Mamoru
• Wave Life Sciences Ltd

Inventors

• Wada Takeshi
• Shimizu Mamoru

Classifications

• C07H1/00

  Processes for the preparation of sugar derivatives · CPC title

• C07D211/44

  attached in position 4 · CPC title

• C07H21/02

  with ribosyl as saccharide radical · CPC title

• C07D207/16

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07D217/24

  Oxygen atoms · CPC title