Compounds, compositions, and methods for synthesis

Abstract

To provide compounds with chiral auxiliaries for the synthesis of oligonucleotides with chiral modified internucleotidic linkages, particularly for stereoselective synthesis, reagents derived from the compound, and synthesis methods using the reagents.SOLUTION: For example, compounds useful as chiral auxiliaries, represented by formula I-a-1, are disclosed. (R1, R2, R4 and R5 each independently represent -H, a halogen, -CN, -NO2 or the like, R6 represents -R(=C1-30 alkyl), -C(O) R, -CO2R, or -SO2R).SELECTED DRAWING: None

Claims

1. Formulas IV-a, IV-b, IV-c-1, IV-c-2, IV-d, or IV-e: 【Chemistry 1】 A compound having the structure or a salt thereof, wherein the formula is: P Ｌ P is, L is -C(R ３ ) (Caution ４ ) - and R １ and R ２ These, together with the carbon atoms to which they are bonded, form a five- or six-membered monocyclic ring that does not contain heteroatoms and is optionally substituted, or a nine- to fifteen-membered bicyclic or tricyclic ring that does not contain heteroatoms and is optionally substituted. R ３ is -H, -L ｓ -R, halogen, -CN, -NO ２ , -L ｓ -Si(R) ３ , -OR, -SR, or -N(R) ２ and R ４ and R ５ Together with the intervening atoms, these form an optionally substituted four- or five-membered monocyclic ring having only one heteroatom, which is the nitrogen to which R5 is bonded, or an optionally substituted seven- to ten-membered bicyclic ring having only one heteroatom, which is the nitrogen to which R5 is bonded. Each L ｓ They are independently, covalently bonded, or C １－３０ C having an aliphatic group and 1 to 10 heteroatoms １－３０ A divalent, optionally substituted linear or branched group selected from heteroaliphatic groups, wherein one or more methylene units are optionally and independently C １－６ Alkylene, C １－６ Alkenylene, -C≡C-, a divalent carbon atom having 1 to 5 heteroatoms. １ -C ６ Heteroaliphatic group, -C(R') ２ -, -Cy-, -O-, -S-, -S-S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O) ２ -, -S(O) ２ N(R')-, -C(O)S-, -C(O)O-, -P(O)(OR')-, -P(O)(SR')-, -P(O)(R')-, -P(O)(NR')-, -P(S)(OR')-, -P(S)(SR')-, -P(S)(R')-, -P(S)(NR')-, -P(R')-, -P(OR')-, -P(SR')-, -P(NR')-, -P(OR') [B(R') ３ ]-, -OP(O)(OR')O-, -OP(O)(SR')O-, -OP(O)(R')O-, -OP(O)(NR')O-, -OP(OR')O-, -OP(SR')O-, -OP(NR')O-, -OP(R')O-, or -OP(OR') [B(R') ３ Replaced by any substituted group selected from ]O-, one or more carbon atoms are optionally and independently Cy Ｌ Replaced by, Each -Cy- is independent of C ３－２０ Alicyclic ring, C ６－２０ A divalent group that is optionally substituted, selected from an aryl ring, a 5-20 membered heteroaryl ring having 1-10 heteroatoms, and a 3-20 membered heterocyclyl ring having 1-10 heteroatoms. Each Cy Ｌ Independently, C ３－２０ Alicyclic ring, C ６－２０ A tetravalent group that is optionally substituted, selected from an aryl ring, a 5-20 membered heteroaryl ring having 1-10 heteroatoms, and a 3-20 membered heterocyclyl ring having 1-10 heteroatoms. Each R' is independently -R, -C(O)R, -C(O)OR, or -S(O) ２ It is R, L ７ is -O- or -S-, BA is a nucleic acid base that can be optionally substituted, selected from A, T, C, G, U, and their tautomers. Each of R1s, R2s, R3s, R4s, and R5s is independently Rs, Each R ｓ These are independently -H, halogen, -CN, and -N ３ , -NO, -NO ２ , -L ｓ -R', -L ｓ -Si(R) ３ , -L ｓ -OR', -L ｓ -SR', -L ｓ -N(R') ２ , -O-L ｓ -R', -O-L ｓ -Si(R) ３ , -O-L ｓ -OR', -OL-L ｓ -SR', or -OL-L ｓ -N(R') ２ And, t is between 0 and 20. Ring A ｓ This is an optionally substituted monocyclic, bicyclic, or polycyclic ring having 0 to 10 heteroatoms, R ５ｓ is R ｓ And, Each R is independently either -H or C １－３０ Aliphatic carbon atoms containing 1 to 10 heteroatoms １－３０ Heteroliphatic, C ６－３０ Ariel, C ６－３０ Aryl aliphatic carbon atoms containing 1 to 10 heteroatoms ６－３０ An optionally substituted group selected from aryl heteroaliphatic groups, 5-30 membered heteroaryl groups having 1-10 heteroatoms, and 3-30 membered heterocyclil groups having 1-10 heteroatoms, or The two R groups, either independently or separately, come together to form a covalent bond, or Two or more R groups on the same atom may, independently and arbitrarily, combine with the atom to form an optionally substituted 3-30 member monocyclic, bicyclic, or polycyclic ring having 0-10 heteroatoms in addition to the atom, or A compound or a salt thereof, wherein two or more R groups on two or more atoms optionally and independently combine with the intervening atoms to form an optionally substituted 3-30 member monocyclic, bicyclic, or polycyclic ring having 0-10 heteroatoms in addition to the intervening atoms.

2. The aforementioned compound is of formula IV-e: 【Chemistry 2】 The compound according to claim 1, having the structure.

3. R ２ｓ However, it is -OR, and R is arbitrarily substituted C １－６ A compound according to any one of claims 1 to 2, wherein it is alkyl.

4. R ２ｓ However, -H, -F, -OMe, or -OCH ２ CH ２ The compound according to any one of claims 1 to 2, wherein the compound is OMe.

5. R ４ｓ The compound according to any one of claims 1 to 4, wherein the compound is -H.

6. The aforementioned compound is of formula IV-d: 【Transformation 3】 It has a structure, R ４ｓ and R ２ｓ These combine and are optionally substituted -O-CH ２ The compound according to claim 1, wherein a - is formed and O is bonded to the carbon at position 2. 【Request Item 7】 【Chemistry 4】 but, 【Transformation 5】 The compound according to claim 6.

8. R ５ｓ The compound according to any one of claims 1 to 7, wherein the compound is DMTrO-.

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