Boronic acid compound having a binaphthyl group

■fllRillilllllll

United States Patent [i9]

James et al.

US005763238A [ii] Patent Number: [45] Date of Patent:

5,763,238 Jun. 9, 1998

BORONIC ACID COMPOUND HAVING A BINAPHTHYL GROUP

FIELD OF THE INVENTION

The present invention relates to a boronic acid compound, and particularly to a novel chiral boronic acid compound capable of binding to polyols. particularly to saccharides, which compound is suitable for use in analysis or separation of the diols.

BACKGROUND OF THE INVENTION

Polyols, as typified by saccharides, widely occur in nature and play an important role in living organisms. They are also one of the key materials used in industry. Polyols are characterized by their complexity and variety. In particular, a saccharide is composed of the D-form and L-form, which are known as optical isomers. The separation of such isomers (optical solution) is of great importance in many fields, such as in synthesizing pharmaceutical substances. The contamination by an undesired optical isomer may cause not only a lowering of the pharmaceutical efficacy but also serious side-effects in the patient. However optical isomers are difficult to selectively isolate or detect, since they have identical physical properties such as boiling point and melting point If it should be possible to selectively detect or isolate a polyol of a specific structure, that is, to selectively detect or isolate the D-form or L-form of isomers, it would not only make a great contribution to the world of science but also arouse a variety of industrial applications. However, no practical measures seem to be available for this purpose.

SUMMARY OF THE INVENTION

One possible approach for the separation and/or analysis of polyols such as saccharides would be the utilization of a substance capable of selectively binding to a target polyol in which the binding can be externally read out.

It is well known that a boronic acid group, B(OH)2. covalently reacts with OH groups present in such compounds as saccharides. Based on this phenomenon, the present inventors previously created a novel phenylboronic acid compound which emits strong fluorescence when combined with glucose (Japanese Patent Application No. 147061/1994). While the compound is suitable for use in the detection of a specific saccharide, it is unable to discriminate between the D-form and L-form of the saccharide.

The present inventors have now succeeded in synthesizing for the first time a novel boronic acid compound which is able to discriminate between the D-form and L-form of a saccharide when necessary.

Thus, according to the present invention there is provided a novel chiral boronic acid compound having a binaphthyl group which can be expressed by the following general formula(l):

10

15

20

40

45

50

In the formula(l), R1 and R2 are generally the same, but may be different. RL and R2 are selected from the group consisting of alkoxy groups having 1 to 4 carbon atoms and OH (hydroxyl group), with methoxy, ethoxy or OH being particularly preferred.

In the above formula(l). n+m is 2 or 3 and x+y is 2 or 3. in which each of n. m. x and y may be zero, n and x are generally the same but may be different, m and y are generally the same but may be different. Most generally, each of n, m. x and y is 1. Thus, a preferred example of the compounds falling within the definition of the formula(l) can be expressed by the following formula(2):

The boronic acid compound having a binaphthyl group of the present invention as expressed by the aforesaid formulas (1) and (2) has a chiral structure. i.e. a mirror-image (enantiomer) structure consisting of R-form (R-isomer) and S-form (S-isomer). Thus, the formula(l) (or formula(2)) expresses either R-form or S-form of the compound. The boronic acid compound of the present invention is characterized by the fact that the R-form and S-form thereof each exhibits an extremely high selectivity to one of the enantiomers of a polyol, particularly of a saccharide.

Specifically, the R-form of the boronic acid compound of the following formula(3) has a high selectivity to D-form of a monosaccharide such as glucose and fructose, and emits an increased fluorescence upon binding to such D-form. while the S-form of the same compound exhibits a high selectivity to L-form of the monosaccharide and emits an increased fluorescence upon binding to the L-form.