DD226887A1 - PROCESS FOR THE PREPARATION OF 1-HALOGENATED GIBBERELLINES - Google Patents

Abstract

It is the object of the invention to produce gibberellin derivatives having altered biological activity. The object of the invention is to introduce chlorine or bromine into position 1 of the ent-gibberellan skeleton. According to the invention, a gibberellin derivative having a D1 (10) -19 acid heterogeneous structural feature is reacted with N-chlorosuccinimide and N-bromosuccinimide and bicarbonate, respectively, to form a 1-halogenated gibberellin having a 1910 lactone ring. 1-Halogenated gibberellins are obtained in good yields when operating at room temperature.

Description

-2- 672 embodiments

example 1

1 ß-chloro-gibbereilin A ₁ (2)

52 mg of diacid 1 are shaken in 4 ml of tetrahydrofuran and 3 ml of methylene chloride with 30 mg of N-chlorosuccinimide (NCS) and 2 ml of 5% aqueous sodium bicarbonate solution for 20 hrs. At room temperature. After distilling off the solvent is acidified with 2N hydrochloric acid and extracted 7 times with ethyl acetate. The combined extracts are washed with water, dried over sodium sulfate, filtered, i. Vak. evaporated and the residue chromatographed on SiO ₂ . Eluting with chloroform / ethyl acetate 1: 1 v / v provides in fractions 69-96 40 mg (70%) ISS chloro-GA, (2) from acetone / n-hexane in needles of mp 230-234 ^0th C and [α] |, ⁵ + 25.1 ^ο (c = 0.288 in ethanol) crystallized. IR (Nujol): v _max 1 702 (carboxyl), 1 765 (7-lactone) and 3420 cm ^-1 (hydroxyl) MS: m / e 382 (M ⁺ ) NMR (200 MHz, acetone-D _e ) : 1.12 (s, 18-H ₃ ), 2.57 (d, J = 10Hz, 6-H), 3.77 (d, J = 10Hz, 5-H), 3.78 (t , J = 4 Hz, 1-H), 4.37 (t, J = 4 Hz, 3-H), 4.88 and 5.18 (δ) ppm (17-H ₂ ).

Example 2 1β-Bromo-gibberellin A ₁ (3)

67 mg of diacid 1 are shaken in 4.5 ml of tetrahydrofuran and 3.5 ml of methylene chloride with 35 mg of N-bromosuccinimide (NBS) and 2.5 ml of 5% aqueous sodium bicarbonate solution for 20 hrs. At room temperature and as described in Example 1 , worked up and chromatographed: 47 mg (57%) of Ip-BrOm-GA ₁ (3) of mp 238-241 ⁰ C (from ether / n-hexane) and [a] §f + 19.2 ° (c = 0.348). IR (nujol): v _max 1708 (carboxyl), 1775 (γ-lactone) and 3500 cm "'(hydroxyl).

MS: m / e 428 and 426 (M ⁺ with ⁸¹ Br and ⁷⁹ Br, respectively). NMR (200 MHz, acetone-D ₆ ): 1.12 (s, 18-H ₃ ), 2.58 (d, J = 10 Hz, 6-H), 3.80 (t, J = 4 Hz, 1-H), 3.87

(d, J = 5Hz, 5-H), 4.48 (d, J = 4Hz, 3-H) ^ 4.89 and 5.20 (δ) ppm (17-H ₂ ).

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Claims (5)

Invention claims: 1. A process for the preparation of 1-halogenated gibberellins, characterized in that a gibberellin derivative with Δ '<ιο) -19 acid structural feature in heterogeneous phase with an N-halogen compound in the presence of alkali metal bicarbonate to a 1- halogenated gibberellin with 19 * 10-lactone ring. 2. The method according to item 1, characterized in that one carries out the reaction in tetrahydrofuran, methylene chloride and water. 3. The method according to item 1 and 2, characterized in that one uses as the N-halogen compound N-chloro-succinimide or N-bromosuccinimide. 4. The method according to item 1-3, characterized in that one carries out the reaction with thorough mixing of the components and at room temperature. 5. The method according to item 1-4, characterized in that as starting material ent-3a, 13-dihydroxy-20-norgibberella-1 (10), 16-diene-7,19-diacid, their O-acyl derivatives or their 7th -Methylester used. For this 1 page formulas Process for the preparation of 1-halogenated gibberellins The invention relates to a process for the preparation of 1-halogenated gibberellins. These are gibberellin derivatives which are substituted in position 1 of the ent-gibberellan skeleton by halogen. In this case, the ent-gibberellan skeleton is intact or slightly modified (eg seco, homo or nor-ent-GibbeVellan) and optionally substituted in various ways (eg 3-epi-gibberellins). Field of application of the invention The compounds produced according to the invention have as growth-regulatory active substances biological interest and practical importance for the control of gibberellinregulierten growth and development processes for agriculture, horticulture and forestry. They also serve as starting materials for the synthesis of further structure-modified gibberellins, which u. a. also suitable for use in affinity chromatography. Characteristic of the known technical solutions Naturally occurring deterpenoids with ent-gibberellan backbones possess biological significance as phytohormones of multiple action (gibberellins). It is known that structural modification of such gibbereilins leads to compounds with altered biological activity. For example, deoxygibberellin C, pseudogibberellin A ₁ , homogibberellin A ₃ , and certain fluorinated species exhibit gibberellin antagonistic properties. Numerous other structurally modified gibberellins have been prepared by partial or total synthetic methods and tested for their biological activity. So led z. B. The reaction of the obtained by hydrogenation of GA ₃ dicarboxylic acid with iodine in methylene chloride / tetrahydrofuran / aqueous sodium carbonate to iβ-iodine GA, (N.MURdFUSHI, I. 'ΥΑΜΑοίΓόΗΙ,'Η'.ΤέΗΪΟΟΟκλ',' Ν: TAKAHAS H Biol. Chem. 40 (12), 2471 (1969) B. KEITH / LM SRIVASTAVA, N. MUROFUSCHI, 43 (1), 141 (1979), NV MINH, Dissertation 1979, Institute of Biochemistry the plants Halles AdW of the GDR). ''""'< However, no method for producing gibberellin derivatives substituted in position 1 of the ent-gibberellan skeleton by chlorine or bromine has been known. Object of the invention It is the object of the invention to provide gibberellin derivatives having altered gibberellin activity as a result of structural modification, both for practical use in the field of plant growth and development regulators and for research. Explanation of the essence of the invention The object of the invention is to produce gibbereiline derivatives which are substituted in position 1 of the ent-gibberellan skeleton by chlorine or bromine. According to the invention, an A ^{1 (10)} -unsaturated gibberellin-19-acid in heterogeneous phase, preferably methylene chloride / tetrahydrofuran / water in the presence of alkali hydrogencarbonate, with an N-halogen compound becomes a 1-halogenated gibberellin with 19-> 10-lactone ring implemented. For the preparation of the 1-chloro-gibbereMine, in particular N-chlorosuccinimide, for the 1-bromo-gibberelline N-bromo-succinimide is used. Suitable starting materials are ent-3a, 13-dihydroxy-20-nor-gibbereila-1 (10), 16-diene-7,19-diacid, their'-O-acyl derivatives or their 7-methyl esters. They are prepared in known manner from GA ₃ (compare Y. HSÜ, N- TAKAHASHI, K. MIYAO, A. KAWARADA, H. KITAMURA, S. TAMURA, Y. SUMIKI, Agric. Biol. Chem. (Tokyo) 25; 865 (1961); Ph. D. HUNG, Dissertation 1974, Institute of Biochemistry of Plants Halle, AdW of the GDR). Further usable gibberellin derivatives with A'f''-ig acid Strukturmerkmai are those which are accessible by hydrogenation of GA ₇ , GA ₃₀ , GA ₃₂ and GA ₉ J or their 7-esters. 1-halogenated gibberellins are obtained in good yields by carrying out the reaction with thorough mixing of the components, such as stirring or shaking, and at room temperature. The isolation of the produced 1-halogenated gibberellins is carried out by known methods. For example, after distilling off the organic solvent, the residue is treated with dil. Hydrochloric acid and extracted with an organic solvent, for example ethyl acetate. After distilling off the solvent, the reaction product is purified by chromatography. By-products were not found. The process according to the invention makes it possible to introduce chlorine or bromine into the 1-position of the gibberellin molecule in order to obtain the functional groups essential for the biological action. The compounds according to the invention have a modified Gibbereilinwirksamkeit due to their modified structure. Thus, they are of interest for practical application in the field of plant growth and development as well as for biochemical research. The invention is explained in more detail by the following exemplary embodiments.