DD135726B1 - PROCESS FOR PREPARING C LOW 19-GIBBERELINALDEHYDE - Google Patents

Description

Inventor:

Dr. M. LISCHWSKI habil. G. ADAM

Process for the preparation of С иг г-Gibberellinaldehyden

The invention relates to a process for the preparation of C.Q gibberellin (7) aldehydes. These are gibberellin derivatives which have an aldehyde group in position 6 of the 20-nor-ent-gibberellan skeleton. The 20-nor-de-gibberellan backbone is intact or slightly modified (e.g., seco-, homo- or nor-pent-gibberellan) and optionally substituted in a variety of ways.

Field of application of the invention

Gibberellins have great biological significance as phytohormones of multiple origin. It is known that structural modification of such naturally occurring gibberellins leads to compounds with altered biological activity. For example, deoxygibberellin C, pseudogibberellin Ai and certain fluorinated species exhibit gibberellin antagonist properties. Numerous other structurally modified gibberellins have been synthesized by partial and total synthetic methods and tested for their biological activity. Furthermore, gibberellins are used in the form of their labeled representatives, e.g. for biotechnological processes, for the investigation of biosynthesis, metabolism, transport, distribution, mode of action and structure / activity analysis of these phytohormones and their partial synthetic structural analogues as a basis for the synthesis of active substances.

Characteristic of the known technical solu tions

C ^ g-gibberellin derivatives with 6-position aldehyde function are known and can be synthesized by the following methods:

1. Reduction of C ^ g gibberellin anhydrides with disodium tetracarbonyl-ferrate (-II) produces C ^ -G-ibberellin- (7) -aldehydes / ~ LI. LISCHEV / SKI and G. ADAM, DDE patent specification 112 753 of 22.5.197 ^; ІЛ. LICHERTSKI and G. ADAM, Tetrahedron Letters 2835 (1974) _7.

2. By oxidation of CL ^ gibberellin derivatives with 6-position hydroxymethyl group by certain sulfonium salts, in particular by the N-chlorosuccinimide-dimethyl sulfide complex, arise C ,, g-gibberellin (7) -aldehydes / "M. LISCHE 77SKI and G. ADAM, GDR Patent 120,875, 29.4.1975 M. LISCHEWSKI and G. ADAI, I, Tetrahedron Letters 2569 (1975), M. LISCHEWSKI and G. ADAM, Z. Chem., 16, 486 (1976 ) _7.

The described methods have the following disadvantages:

To 1: The C ^ g-gibberellin ~ (7) -aldehydes formed in this way are produced in low yield and are also difficult to isolate, so that the aldehydes in this process immediately reduced to C, .Q-gibberellin (7) -alcohols become.

To 2: A by-product of this process is a 6β- / ω-tetrahydroxy-methoxy-1-hydroxy-7-yl-7-ylbigene 11 in derivative.

Object of the invention

It is the object of the invention to develop a generally applicable process which enables the production of G.q. Gibbereilin derivatives with 6-stage aldehyde group in high yield and without by-products.

Loan of the invention

The object of the invention is to oxidize G ^ Q-gibberellin derivatives with 6-position hydroxymethyl group specifically to CnQ gibberellin (7) aldehydes.

According to the invention, a C.q. gibberellin derivative having a 6-membered hydroxymethyl group is reacted with a chromium-containing oxidizing agent to give C, Q-gibberellin (7) -aldehyde.

The C ^ q-gibberellin derivatives with 6-position kydroxymethyl group used as starting materials are synthesized by known methods. LISCHEüSKI and G. ADAM, DDE Pat. No. 112 753 of May 22, 1974; Ы. LISCHE7 / SKI and G. ADALI, DDE Pat. No. 121,784 of July 4, 1975; M. LISCHEV / SKI and G. ADAM, Tetrahedron Letters 2835 (1974); M. LISCHEWSKI and G. ADAM, Tetrahedron Letters 3691 (1975); M. LISCHEV / SKI and G. ADAM, Z. Chem. 16i (1976), 486_7.

The oxidation is carried out in a solvent which is not oxidizable under the conditions used, for example methylene chloride or chloroform. Chromium-containing agents are used as the oxidizing agent, for example chromium (VI) oxide, pyridinium chlorochromate or the ear oxide / pyridine complex (CrO ₁ -'Py).

Furthermore, the reaction temperature can be varied within a wide range, with the most expediently being carried out at room temperature. When using C ^ q-gibberellin derivatives with other oxidation-sensitive hydroxyl groups, it is advantageous to provide them with a protective group prior to oxidation. Examples of protective groups are acyl groups, such as acetyl, propionyl or benzoyl, silyl groups, such as trimethylsilyl, or the tetrahydropyranyl group. For example, the hydroxyl group located at the C-3 must in 6іЗ-Нусгoxyme "nnyl- (7) -nor-gibberellin-Ao or in 6ß-hydroxymethyl be protected (7) -nor-gibberellin A ^ to this 7» ^T else.

The workup of the reaction products by the usual methods, for example by column chromatography using organic solvents.

The process according to the invention is generally applicable and gives the desired G _x , g-gibberellin (7) aldehydes in high yield and without by-products.

The compounds shown as growth-regulatory active substances with partly gibberellin-antagonistic properties of biological interest and practical importance for the control of gibberellin-regulated 7 / achstums- and development processes. They also serve as starting materials for the synthesis of other structurally modified gibberellins and radiolabeled analogues.

The following examples illustrate the invention, wherein the specific conditions specified therein do not limit the invention.

Ausführungsbe games

Example 1

A solution of 416.5 mg (1 mmol) of O (3) jO (13) -diacetyl-6ß- is added dropwise with stirring and argon atmosphere to 4-31.2 mg (2 mol) of pyridinium chlorochromate in 5 ml of dry GHpGl ^ hydroxymethyl (7) -nor-gibberellin Ao (I) in 5 ml of dry CHpCIg. After 2 hours, the mixture is mixed with 50 ml of ether. After separating the ether phase, the residue is extracted several times with fresh ether. The combined ether extract is extracted several times with water, dried and concentrated, and subsequent chromatography of the residue on 20 g of silica gel (Woelm) gives, on elution with n-hexane / chloroform, 40:60 v / v 338 mg = 87 % of theory . Th. (Yield calculated on reacted alcohol compound) 0 (3) -Diacetyl gibberellin-A ₃ - (7) -aldehyde (IV) / "Mp: 162-164 ⁰ G (ether / n-hexane) ; [ρί] ψ + 204.8 ° (c = 0.542, abs dioxane) _7 and with chloroform 26 mg unreacted O (3), 0 (13) -diacetyl-6β-hydroxymethyl- (7) -nor-gibberellin Ao ·

BeisDiel2

To 660 mg (3%) of the chromium peroxide / pyridine complex (CrO _n - * Py) in 20 ml of GH ₂ Cl _{2 is} added, in ethyl acetate, 940 mg (2.5 mg / l) of 6β-hydroxymethyl- (7) -or-gibber IUn-A ₅ (II) in 50 ml CH ₂ Cl ₂ . After 5 hours, the mixture with dil. HCl, sat. NaHCOv solution and V / asser shaken. Subsequent drying over Na ₂ SO. and subsequent concentration of the CH ₂ Cl ₂ phase yields a residue which is chromatographed on 50 S silica gel (v / oelm). Slution with hexane / CHCl ^ 1: 9 v / v provides 78? mg (81% of theory) gibberellin A ₅ - (7) -aldehyde (Y) / "amorphous product, [$ ψ -36.8 ° (с = 0.53, ethanol) with CHCl ₃ 48 mg of 6β-hydroxymethyl (7) -nor-gibberellin A ₅ (II).

30.2 mg (0.1 ml) of 6β-hydroxymethyl (7) -nor-gibberellin Aq (III) are reacted at room temperature in 3 dl of hexamethylphosphoric triamide with 30 mg (0.3 mmol) of CrO 2. After stirring for 2 hours, the mixture is chromatographed on 1 g of silica gel (v / oelm). Chromatography with hexane / CPICI ^ 1: 1 v / v gives 24 mg (80 % of theory) of gibberellin ao (7). aldehyde (YI) /, "amorphous product; \ ς§ψ + 17.3 ° (c = 0.42, ethanol) _7.

Claims (4)

Claim 1. A process for the preparation of CLg-Giboerellinaldehyden, characterized in that a (L · g-gibberellin derivative having 6-hydroxyethyl in a solvent with a chromium-containing oxidizing agent for
C _x jQ-gibberellin ~ (7) -aldehyde is reacted. 2. "Process according to item 1, characterized in that used as the oxidizing agent pyridinium chlorochromate
becomes. 3. The method according to item 1, characterized in that the oxidizing agent of the chromium peroxide / pyridine complex 'Py) is used. 4. Process according to item 1, characterized in that the oxidizing agent used is Ohrom (VI) oxide. For this ../."...Siten formulas