JPS63211263A - Novel dipeptide - Google Patents

Abstract

NEW MATERIAL:A compound shown by the formula and a pharmaceutically acceptable salt thereof. EXAMPLE:Prolyltaurine. USE:A plant growth regulator. PREPARATION:Proline or hydroxyproline is reacted with taurine by the use of ordinary peptide condensation method such as azide method, active ester method, mixed acid anhydride method, acid chloride method or a method using condensation agent such as dicyclohexylcarbodiimide or water-soluble carbodiimide to give a compound shown by the formula.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a novel dipeptide having plant growth regulating activity.

(Prior Art) Rice is the most important grain in Japan, and efforts are being made to improve rice varieties and develop growth regulators. It goes without saying that the roots of rice are important in wet rice cultivation, but varieties with strong roots have many advantages when transplanted to paddy fields, for example.

The present inventors, while searching for compounds that have a beneficial plant growth regulating effect, discovered that the compound of the present invention has a useful effect of enriching the roots, and completed the present invention.

(Problems to be Solved by the Invention) An object of the present invention is to provide a novel dipeptide having a plant growth regulating effect.

(Means for Solving the Present Invention) The compound of the present invention is a novel dipeptide represented by the following general formula (1).

(In the formula, R represents hydrogen or a hydroxyl group.) The dipeptide of the present invention includes pharmaceutically acceptable salts of the compound represented by the general formula N), such as inorganic salts containing alkali metals such as sodium and potassium. , salts with alkaline earth metals such as calcium and barium, other metals such as aluminum, and salts with organic amines such as ammonium.

Further, the compound of the present invention includes its metal complex compounds, such as complex compounds with zinc, nickel, cobalt, copper, iron, etc.

These salts and metal complex compounds can be produced from the free dipeptide of the present invention by known methods, or can be converted into each other.

The amino acid residue in the present invention may be any one of D, L, and DL.

The dipeptide of the present invention represented by formula (1) above can be produced by condensing proline or hydroxyproline with taurine. Examples of the condensation method include the azide method, active ester method, mixed acid anhydride method, and acid chloride method. 17)' method, a method using a condensing agent such as dicyclohexylcarbodiimide (DCC) or water-soluble carbodiimide (WSCD), and other conventional peptide condensation methods can be used.

Amino acids that serve as raw materials for the condensation reaction can be those that have commonly used protecting groups, and side chain functional groups that do not participate in the reaction can be protected by known methods, or carboxyl groups that participate in the reaction can be protected. group, amino group may be activated.

These substituents can be removed by conventional means such as catalytic reduction and acid decomposition.

For example, as the N-protecting group for the pyrrole ring of proline and hydroxyproline, protecting groups used in normal peptide synthesis can be used, such as benzyloxycarbonyl, t-butoxycarbonyl, p-nitrobenzyloxycarbonyl, p- Examples include methoxybenzyloxycarbonyl group.

Condensation reaction and debinding! ! ! The reaction temperature, time, solvent, etc. in the group reaction can be set according to reaction conditions used in ordinary peptide synthesis.

An example of the method for producing the dipeptide of the present invention is shown below.

In a suitable solvent such as tetrahydrofuran or dioxane that does not inhibit the reaction, N-hydroxy-5-norbornene-2,3-dicarboximide is added to proline or hydroxyproline containing the above N-protecting group such as t-butoxycarbonyl group. An active ester alcohol component such as (HONB) and a condensing agent such as DCC are added and reacted to convert the carboxyl group into active ester. After adding taurine and performing peptide condensation, the dipeptide of the present invention can be obtained by simultaneously desalting and deprotecting by treating with an acid such as hydrochloric acid and passing through a cation exchange resin.

The obtained compound of the present invention is purified by conventional means such as chromatography and recrystallization, and subjected to elemental analysis, melting point, and R%.
Identification was performed using NMRSUV, mass spectrometry, etc.

Note that the specific optical rotation was measured using the D line of sodium.

(Example) Examples of the manufacturing method of the present invention are shown below.

Example 1 6.46 g of t-butoxycarbonylproline and 5.
91 g of HONB was dissolved in a mixed solvent of tetrahydrofuran 75- and dioxane 75-, and 6.81 g was dissolved under water cooling.
of DCC was added. After stirring for 20 minutes under water cooling and 40 minutes at room temperature, the resulting dicyclohexyl urea was filtered off.
The solvent was distilled off under reduced pressure. Dissolve the residue in dioxane 75 and prepare an aqueous solution of taurine sodium salt 5 prepared from 3.75 g taurine and 2.52 g sodium bicarbonate.
0- was added at room temperature and stirred for 20 hours. After filtering off insoluble matter, the solvent was distilled off under reduced pressure. The residue was dissolved in 100 d of water, adjusted to pH 2 with 6N hydrochloric acid, and washed with ethyl acetate. The aqueous layer was passed through a cation exchange resin for simultaneous desalting and deprotection. The eluate was concentrated under reduced pressure to precipitate white crystals, which were filtered from ethanol and recrystallized from water-ethanol to obtain 4.66 g of prolyl taurine (compound 1).

Yield near 0% Melting point: 242-244℃ (α) ”: -44,8” (C=1.0.Hx
O) NMR (0, INDCI, t-BuOH-1,2
3ppm): δ-4, 38-4, 32 (IH, resistance,
3.66 (LH, ddd, J-6, 5°6.5.14H
z), 3.61 (IH, ddd, J-6, 5, 6, 5
゜14Hz), 3.48-3.33 (2H, m),
3.10 (211, t.

J-6,5Hz), 2.46-2.35(IH, m
), 2.12-2.00 (3H4) Elemental analysis: 0% 11% N% as Ct HIa N t Oa S Calculated value: 37.83 6.35 12.60 Actual value: 37.51 6.04 12 .37 Example 2 12.38 g of t-butoxycarbonylhydroxyproline dicyclohexylamine salt was dissolved in a mixed solvent of 150-tetrahydrofuran and 150-dioxane, and 5.71 g of toluenesulfonic acid 1-hydrate was added under water cooling. added. To this, water-cooled HON B5.91 g, D
6.81 g of CC was successively added, and the mixture was stirred for 20 minutes under water cooling and for 40 minutes at room temperature. The resulting insoluble matter was filtered off, and the solvent was distilled off under reduced pressure. Dissolve the residue in 150 liters of dioxane,
An aqueous solution of taurine sodium salt prepared from 3.75 g of taurine and 2.52 g of sodium bicarbonate 5
0- was added at room temperature and stirred for 20 hours. After filtering off insoluble matter, the solvent was distilled off under reduced pressure. Water the residue 100++
d, adjusted to pH 2 with 6N hydrochloric acid, and washed with ethyl acetate. The aqueous layer was passed through a cation exchange resin for simultaneous desalting and deprotection. The eluate was concentrated under reduced pressure to precipitate white crystals, which were filtered from ether and recrystallized from water-ethanol to obtain 5.14 g of hydroxyprolyl taurine (compound 2).

Yield near 2% Melting point: 27B -280℃ (decomposition) [α] Mushroom':
35.5 @(C-1,0,Hid)NMR(0,
lN0CI, t-BuOIl=1.23 ppm)
: δ-4,70(IH, dddd, J-4,4,1,5
, 1,511z).

4.57 (18, dd, J-7, 10Hz), 3.6
7 (18, ddd.

J-6, 5, 6, 5, 14H2), 3.62 (III
, ddd, J-6, 5°6.5.14Hz), 3.5
0 (IH, dd, J-4, 1382).

3.41 (1B, ddd, J-1, 5, 1, 5, 13H
z), 3.10 (2H.

t, J=6.5Hz), 2.47(IH, dddd,
J-1,5,1,5°7,14Hz), 2.18(I
H, ddd, J-4, 10, 1411z) Elemental analysis:
C? 0% as H+ a N * Os S
6% N% Calculated value: 35.29 5.92 11.76
Actual value + 35.18 5.98 11.74 (
Effect) Using rice grown in 1985 (Nipponbare) stored at 4℃,
The plant growth regulating effect of the compounds of the present invention was investigated.

A filter paper soaked with an aqueous solution of the test drug (1xlO-''M) was placed in a Petri dish to serve as a germination bed, and test seeds were sown.

Five of the seeds that germinated between the second and third day were transferred to a plant culture test tube containing a test aqueous solution with the same concentration as that at the time of germination, and a growth test was conducted.

Six days after transplantation, the length and weight of the aboveground and underground parts were measured. The test was conducted in the dark at 27°C, and was repeated six times to determine the average value and standard error.

An example of the results is shown in Table 1.

Table 1 Control (distilled water) Compound l Aboveground part (m) 55.0±1.07 53.5
±1.50 underground weight (sg) 25.1 ±0.7
6 25.3±0.88 seeds m (m) 54
．． 4±3.30 47.9±2.25 Underground weight (s
g) 16.5±1.50 20.0±1.63(
, Effect) As is clear from the above results, the compound of the present invention has the effect of increasing the weight of the underground part (root part) of rice plants and shortening and thickening the length of the seed plate. That is, by administering the compound of the present invention, the roots of rice plants became thick and strong, and this effect was clearly observed in actual observation with the naked eye. In addition, the compound of the present invention does not act on the above-ground parts and therefore does not cause problems such as elongation of the above-ground parts, so it is useful for growing and cultivating plants that have strong root growth and are resistant to wind damage.

Claims (1)

[Claims] (1) General formula (I): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R represents hydrogen or a hydroxyl group.) A compound represented by: and a pharmaceutically acceptable salt thereof.