Stereodynamic chemosensors

Patent metadata

Field	Value
Publication number	US-9815746-B2
Application number	US-201414776538-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 15, 2013
Publication date	Nov 14, 2017
Grant date	Nov 14, 2017

Abstract

The present invention relates to multifunctional chemosensors that can measure the concentration, enantiomeric excess (ee), and absolute configuration of chiral compounds. The chemosensors described herein may contain a backbone moiety that is bonded to a fluorescent moiety and a moiety for bonding a chiral compound. Backbone moieties may include aromatic groups, for example, naphthyl. The chemosensors described herein are useful for measuring concentration, enantiomeric excess, and absolute configuration of organic molecules in areas such as high throughput screening.

First claim

The invention claimed is:

1. A chemosensor compound of formula (I):

wherein
R 1 and R 5 are independently hydrogen, halo, cyano, (C 1 -C 3 ) alkyl, (C 2 -C 3 ) alkenyl, or (C 2 -C 3 ) alkynyl;
R 2 and R 4 are independently hydrogen, —CO 2 R 9 , —C(O)N(R 9 ) 2 , —NR 9 —(C═NR 9 )N(R 9 ) 2 , —NR 9 —(C═O)OR 9 , —O—(C═O)N(R 9 ) 2 , —C(O)R 9 , C(O)CF 3 , —(C═NH)R 9 , N(R 9 ) 2 , OR 9 , or SR 9 , wherein at least one R 2 and R 4 is not hydrogen;
R 3 is —CO 2 R 9 , —C(O)N(R 9 ) 2 , —NR 9 —(C═NR 9 )N(R 9 ) 2 , —NR 9 —(C═O)OR 9 , —O—(C═O)N(R 9 ) 2 , —C(O)R 9 , C(O)CF 3 , —(C═NH)R 9 , N(R 9 ) 2 , OR 9 , or SR 9 ;
each R 6 is independently hydrogen, halo, cyano, (C 1 -C 3 ) alkyl, (C 2, -C 3 ) alkenyl, or (C 2 -C 3 ) alkynyl;
R 7 and R 8 are independently hydrogen, (C 1 -C 6 ) alkyl, (C 2 -C 6 ) alkenyl, (C 2 -C 6 ) alkynyl, aryl, heteroaryl, cyano, nitro, halo, or trihalomethyl;
each R 9 is independently hydrogen, alkyl, or aryl; and
Z is a fluorescent moiety and/or a UV active moiety,
wherein Z and Z′ are different.

2. The compound of claim 1 ; wherein
R 1 and R 5 are independently hydrogen or methyl;
R 2 and R 4 are independently hydrogen, —CHO, or (CO)(C 1 -C 6 ) alkyl, wherein at least one R 2 and R 4 is not hydrogen;
R 3 is NH(R 9 ) or OH,
wherein R 9 is hydrogen, (C 1 -C 6 ) alkyl, or aryl;

R 6 is hydrogen or methyl;
R 7 and R 8 are hydrogen; and
Z is an aryl or heteroaryl group,
wherein the aryl or heteroaryl group may be substituted or unsubstituted.

3. The compound of claim 1 ; wherein Z is anthracene, a quinoline N-oxide, an isoquinoline N-oxide, or a pyridyl-N-oxide.

4. The compound of claim 1 ; wherein Z is isoquinoline N-oxide or 4′-pyridyl-N-oxide.

5. The chemosensor of claim 1 ; wherein the chemosensor is a compound of formula (II):

wherein Z is a fluorescent moiety and/or a UV active moiety.

6. The chemosensor of claim 1 ; wherein the chemosensor of formula (I) is a compound of formula 3:

7. The chemosensor of claim 1 ; wherein Z is achiral.

8. The chemosensor of claim 1 ; wherein the chemosensor compound undergoes racemization and/or diastereomerization in less than about one hour.

9. The chemosensor of claim 5 ; wherein Z is achiral.

10. The chemosensor of claim 5 ; wherein the chemosensor compound undergoes racemization and/or diastereomerization in less than about one hour.

11. A method of providing stereoselective recognition of a stereoisomer of a chiral compound;
wherein the method comprises combining a compound of formula (I) from claim 1 with a sample comprising the chiral substrate compound as a mixture of stereoisomers, and
wherein the compound of formula (I) preferentially binds the stereoisomer to form an adduct.

12. The method of claim 11 ; wherein the method further comprises a step for determining the enantiomeric excess (ee) and diastereomeric excess (de) of the major stereoisomer of the chiral compound by fluorescence spectroscopy, circular dichroism (CD) spectroscopy, and/or ultraviolet (UV) spectroscopy.

13. The method of claim 11 ; wherein the method further comprises a step for determining the total concentration of the stereoisomer by fluorescence spectroscopy or UV spectroscopy.

14. The method of claim 11 ; wherein the method further comprises a step for determining the absolute stereochemistry of the stereoisomer of the chiral compound by CD spectroscopy, fluorescence spectroscopy, and/or UV spectroscopy.

15. The method of claim 11 ; wherein the method further comprises:
(i) isolating the adduct;
(ii) cleaving the adduct;
(iii) separating the compound of formula (I) and the stereoisomer of the chiral compound; and
(iv) isolating the stereoisomer of the chiral compound.

16. The method of claim 11 ; wherein the compound of formula (I)/chiral compound adduct is diastereomeric with a diastereomeric excess (de) of at least 50% de.

17. The method of claim 15 ; wherein the isolated stereoisomer of the chiral compound has an enantiomeric excess of at least 50% ee.

18. The method of claim 11 ; wherein the method further comprises determining two or more of the following properties of the chiral compound:
enantiomeric excess (ee) and/or diastereomeric excess (de) of the major stereoisomer;
the total concentration of the major and/or minor stereoisomer; and/or
the absolute stereochemistry of the major and/or minor stereoisomer.

19. The method of claim 11 ; wherein the chiral compound has an amine, an amide, a carboxylic acid, an amino alcohol, an amino acid, a thiol, an aldehyde, a ketone or an alcohol function.

20. The method of claim 11 ; wherein the chiral substrate compound is an amino alcohol.

Assignees

• Univ Georgetown

Inventors

• Wolf Christian
• Bentley Keith W

Classifications

• C07D217/16

  substituted by oxygen atoms · CPC title

• C07D217/10

  Quaternary compounds · CPC title

• C07B57/00 Primary

  Separation of optically-active compounds · CPC title

• C07C47/57

  polycyclic · CPC title

• C07D213/89

  with hetero atoms directly attached to the ring nitrogen atom · CPC title