DD237654A1 - PROCESS FOR THE PREPARATION OF 1,2-METHYLENE GIBBERELLINES - Google Patents

Abstract

With the aim of producing gibberellin derivatives having altered biological activity, gibberellin derivatives are synthesized which are substituted in position 1,2 of the ent-gibberellan backbone by a methylene moiety. According to the invention, a gibberellin derivative with D1 (2) double bond is reacted with ethereal diazomethane solution to give the 1,2-pyrazoline derivative, which is converted into the 1,2-methylene compound by irradiation with UV light.

Description

embodiments example 1

360 mg of GA _3- methyl ester (1) are reacted in 20 ml of methanol with 4 ml of an ethereal diazomethane solution with exclusion of light at room temperature for 6 days. After distilling off the solvent, the residue is chromatographed on 20 g of SiO ₂ (fractions to 10 ml). Elution with chloroform / ethyl acetate in the fractions 46-58 gives 117 mg of unreacted 1 and in fractions 64-85 268 mg (66%) of 1a, 2a-pyrazoline adduct 2 prepared from acetone / n-hexane in Rods of mp. 242-245 ° C (dec.) And [a] I ³ + 136.9 ° (c = 0.232, ethanol) crystallized. IR (nujol): ymax 900 (> C = CH ₂ ), 1550 (N = N), 1720 (COOCH ₃ ), 1770 (γ-lactone) and 3500cm- ¹ (OH). UV (c = 0.810, methanol): Amax 263 and 327nm, ξ _Μ 238 and 357. MS: m / z 403 (M ⁺ + 1), 402 (M ⁺ ), 374 (M ⁺ - N ₂ ), 356 ( 374 - H ₂ O), 343 (403-HCOOCH ₃ ); 402 (M "), 401,400,374,360 (M ⁺ - CH ₂ N ₂ ), 342 (360 - H ₂ O).

59 mg of pyrazoline derivative 2 are irradiated in 10 ml of acetonitrile under argon in the Pyrex flask for 5 hours with UV light (> 300 nm). After distilling off the solvent, the residue on 3g SiO ₂ chromatography (fractions to 2 ml). Elution with chloroform / ethyl acetate / vials in fractions 37-50 gives 27 mg (50%) of 1a, 2a-methylene-gibberellin methyl ester (3), that of acetone / n-hexane in long needles of mp 229-232 ° C and [a] o ⁶ + 43, O ⁰ C (c = 0.616, ethanol) crystallized. IR (nujol): Qrnax 1705 (COOCH ₃ ), 1750 (y-lactone) and 3440cm- ¹ (OH). MS: m / z374 (M ⁺ ), 360 (M ⁺ -CH ₂ ), 356 (M ⁺ -H ₂ O), 342 (M ⁺ -CH ₃ OH), 328 (360-CH ₃ OH), 314 ( M ⁺ -HCOOCH ₃ ), 296 (356-HCOOCH ₃ ); 374 (M "), 360 (M ^- -CHj), 316 (360-CO ₂ ).

Formulas to the examples

CH ₂ N ₂ \

CO

COOCH ₃

h-v

CH ₃ CN HO ·

COOCH ₃

^H COOCH ₃

Claims (2)

Invention claim: 1. A process for the preparation of 1,2-methylene-gibberallinen, characterized in that reacting a gibberellin derivative with A ^{1 (2)} double bond in organic solution with an ethereal solution of excess diazomethane zurri 1,2-pyrazoline derivative , which is converted by irradiation with UV light in an aprotic organic solvent in the 1,2-methylene compound. 2. The method according to item 1, characterized in that one carries out the addition of the Diazomethansin methanol and the photochemical reaction in acetonitrile and under inert gas. For this 1 page formulas The invention relates to a process for the preparation of 1,2-methylene-gibberellins. These are understood to mean gibberellin derivatives in which the 1,2-position of the ent-gibberellan skeleton is substituted by a methylene moiety and thus forms part of a prop ring-fused cyclopropane ring. The de-gibberellan backbone is intact or slightly altered (e.g., seco, homo or nor-ent gibberellan) and optionally substituted in various ways. 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 structurally modified gibberellins. Characteristic of the known technical solutions Naturally occurring diterpenoids with ent-gibberellan backbone have great biological significance as phytohormones of multiple action (gibberellins). It is known that structural modification of such gibberellins leads to compounds with altered biological activity. For example, deoxygibberellin C, pseudogibberellin Α _Ί , 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. In the . Reaction of GA ₃ methyl ester or diacetyl GA ₃ with diazomethane was obtained in low yield products whose structure was not completely determined but whose physical constants indicated the presence of a pyrazoline derivative (BECROSS, JF GROVE, A. MORRISON, J. Chem.Soc. (London) (1961), 2498; EP SEREBRYKOV, M. LISCHEWSKI, G.ADAM, Izv. AT SSSR, Ser. Khim., 9, 2181 [1978]). The photochemical reaction of 3-dehydro GA ₃ or its methyl ester with ethylene or acetylene led to the corresponding cis-permanent epimeric cyclobutane or cyclobutene derivatives (B. VOIGT, G. ADAM, Tetrahedron Letters 24, 1937 (1975) and E ₁ P-SEREBRYAKOv ₁ VFKUCHEROV, G.ADAM, Izv to SSSR, Ser. Khim., 8, 1831 [1977]).
However, no method for the preparation of gibberellin derivatives with 1,2-methylene grouping is 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 gibberellin derivatives substituted in position 1,2 of the ent-gibberellan backbone by a methylene moiety. According to the invention, a gibberellin derivative with Δ ^{1 (2)} double bond in organic solution, preferably in methanol, with an ethereal solution of excess diazomethane to 1,2-pyrazoline derivative reacted by irradiation with UV light in an aprotic organic Solvent, for example in acetonitrile, is converted into the 1,2-methylene compound. Suitable starting materials are gibberellin derivatives with A ^{1 (2-} l ^double bond, their O-acyl derivatives or 7-esters.) If the addition of the diazomethane in methanol is carried out at room temperature, good yields of 1 are obtained with a reaction time of about 150 hours The reaction to the corresponding 1,2-methylene-gibberellin is generally carried out at room temperature and under protective gas, in particular under nitrogen or argon, and uses for the irradiation UV light with A> 300 nm. The isolation of the compounds prepared by known methods. For example, the reaction product is purified by distilling off the organic solvents by chromatography. The process according to the invention makes it possible, for example, to introduce a 1a, 2a-pyrazoline ring and to subsequently photochemically convert it to the 1α, 2a-methylene-GA _r methyl ester to give the functional groups essential for the biological action. Due to their modified structure, the compounds according to the invention have altered gibberellin activity. Thus, they are of interest for practical application as plant growth and development regulators as well as for biochemical research.