Methods and systems for sulfimidation or sulfoximidation of organic molecules

Patent metadata

Field	Value
Publication number	US-10501762-B2
Application number	US-201615208573-A
Country	US
Kind code	B2
Filing date	Jul 12, 2016
Priority date	Feb 18, 2014
Publication date	Dec 10, 2019
Grant date	Dec 10, 2019

Abstract

The disclosure generally relates to the fields of synthetic organic chemistry. In particular, the present disclosure relates to methods and systems for the imidation of sulfides.

First claim

What is claimed is:

1. A method for catalyzing the intermolecular insertion of nitrogen into organosulfur substrates to produce a product having a new S-N bond, the method comprising:
providing a mixture comprising a nitrene source, an organosulfur substrate and a heme enzyme comprising the amino acid sequence of SEQ ID NO: 1 or an engineered heme enzyme comprising the amino acid sequence of SEQ ID NO: 1 with the exception of at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or all of the following amino acid substitutions in the amino acid sequence of SEQ ID NO: 1 L V78A, F87C, P142S, T175I, A184V, S226R, H236Q, T438S, E252G, A290V, L353V, I366V, C400X, T438S and E442K, wherein “X” is any amino acid other than Cys; and
reacting said mixture for a time sufficient to form a product having a new S-N bond.

2. The method of claim 1 , wherein said nitrene source is an azide.

3. The method of claim 2 , wherein said azide has the general formula R 1 —N 3 ,
wherein R 1 is:
(i) a substituted or unsubstituted aryl, a substituted or unsubstituted aryl, —OR 2 , or —NR 2 , wherein R 2 is a substituted or unsubstituted aryl, a substituted or unsubstituted alkyl;
(ii) —SO 2 R 3 , wherein R 3 is a substituted or unsubstituted aryl, a substituted or unsubstituted alkyl, —OR 2 , or —NR 2 , wherein R 2 are any alkyl or aryl;
(iii) —COR 4 , wherein R 4 is a substituted or unsubstituted aryl, a substituted or unsubstituted alkyl, —OR 2 , or —NR 2 , wherein R 2 are any alkyl or aryl; or
(iv) —P(O)(OR 5 )(OR 6 ), wherein R 5 and R 6 are independently H, a substituted or unsubstituted aryl, a substituted or unsubstituted alkyl.

4. The method of claim 3 , wherein said azide has a structure selected from the group consisting of:

wherein R 1 is any alkyl, aryl, —OR, NR 2 , wherein R, R 2 and R 3 are any alky, or aryl.

5. The method of claim 1 , wherein said nitrene source is selected from the group consisting of:

wherein R 1 is any alkyl, aryl, —OR, NR 2 , wherein R, R 2 and R 3 are any alkyl, or aryl.

6. The method of claim 1 , wherein said product having a new S-N bond is an aliphatic amine and said nitrene source is tosyl azide.

7. The method of claim 1 , wherein said product having a new S-N bond is generated through a nitrenoid intermediate.

8. The method of claim 1 , further comprising expressing said heme enzyme in a bacterial, archaeal or fungal host organism.

9. The method of claim 1 , wherein said engineered heme enzyme comprises a T268A mutation, a T438S mutation and/or a C400X mutation in the amino acid sequence of SEQ ID NO: 1 , wherein X is any amino acid other than Cys.

10. The method of claim 1 , wherein said product having a new S-N bond is a compound of Formula Ia:

wherein R 1 is a sulfoxide, a carbonyl or a phosphonate; wherein R 2 is H or any alkyl or aryl; and
wherein R 3 is H, O or an optionally substituted aryl group.

11. The method of claim 10 , wherein R 1 is a sulfoxide of formula SO 2 R 5 , wherein R 5 is any alkyl, any aryl, —OR 6 or NR 7 , wherein R 6 and Ware any alkyl or any aryl.

12. The method of claim 10 , wherein W is a phosphonate of formula P(O)(OR 8 )(OR 9 ), wherein R 8 and R 9 are independently any aryl or any alkyl.

Assignees

• The California Institute Of Tech
• California Inst Of Techn

Inventors

• Farwell Christopher C
• Mcintosh John A
• Arnold Frances H

Classifications

• C12P13/001 Primary

  Amines; Imines · CPC title

• C12Y106/02004

  NADPH-hemoprotein reductase (1.6.2.4), i.e. NADP-cytochrome P450-reductase · CPC title

• C12Y114/14001

  Unspecific monooxygenase (1.14.14.1) · CPC title

• C12P13/00

  Preparation of nitrogen-containing organic compounds · CPC title

• C12N9/0042 Primary

  NADPH-cytochrome P450 reductase (1.6.2.4) · CPC title