DD154217A1 - PROCESS FOR PREPARING UNSATURATED 1-OXYGENIZED GIBBERELLINE - Google Patents

Abstract

For practical application in the field of plant growth and development regulators, gibberellin derivatives which have an oxo or a hydroxyl group in position 1 of the gibberellin basic skeleton and a double bond in the 2,3 position are to be provided. According to the invention, gibberellin derivatives having a 1-oxo and a 3-hydroxyl group, for example those having 3-hydroxy-1-oxo-20-nor-19 -> 10-lactone structural feature, with a dehydrating agent, e.g. As acetic anhydride or silica gel, dehydrated and thereby converted into the corresponding 1-oxo-delta high 2 compounds. Optionally, subsequently complexed metal hydrides, in particular sodium borohydride, are used to reduce high-2-gibberellins to 1-hydroxy-delta. The compounds according to the invention have an altered gibberellin activity due to their modified structure.

Description

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The invention relates to a process for preparing unsaturated 1-oxygenated gibberellins. This is to be understood in this description of the invention gibberellin derivatives having in position 1 of the ent-gibberellan backbone an oxo or a hydroxyl group and also in the 2,3-position a double bond. The ent-gibberellan backbone is intact or slightly modified (e.g., seco, homo or nor-ent gibberellan) and optionally substituted in a variety of 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 gibberellinregulated Y / achstums- and development processes and for the development of new growth regulators for agriculture, horticulture and forestry. They also serve as starting materials for the synthesis of further structure-modified. Gibberellins, which i.a. also suitable for use in affinity chromatography.

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Characteristic of the known technical solutions

Naturally occurring diterpenoids with ent-gibberellan backbone "have great biological importance as phytohormones of multiple action (gibberellins). It is known that structural modification of such gibberellins results in compounds having altered biological activity, for example, deoxygibberellin C, pseudogibberellin A., and certain fluorinated species exhibit gibberellin antagonist properties.

Numerous other structurally modified gellins have been prepared by partial or total synthetic methods and tested for their biological activity. Thus, for example, acid catalyzed hydration of 3-dehydrogibberellin A ~ with 2N hydrochloric acid in tetrahydrofuran and subsequent reduction with sodium borohydride "1β-hydroxy-gibberellin A and 1β-hydroxy-pseudogibberellin A ^ were synthesized (G. ADAM and PH.D. HTJKG, GDR Patent 112 439, C 07d, 5/06; G. ADM and PH.D. HUIiGy Tetrahedron Letters 1974, 3419). 1β-Hydroxy-gibberellin A ^ can also be prepared by reacting the gibberellin A in the partial hydrogenation. lactone ring opening to give 7.19-diacid with m-chloroperbenzoic acid in dioxane / benzene, and the same authors also isolated 1β-hydroxy gibberellin A. as natural gibberellin (Gibberellin A ₅₅ ) (MUROFUSHI, M. SU-GIMOTO , K. ITOH ₅ W. "TAKAHASHI, Agric. Biol. Chem. 43 (10), 2179 (1979).

The preparation of some skeletally rearranged 1-oxo-gibberellin derivatives has been described (J.R. BEARDER, J. Mac MILLM, C. von CARTENW-LICHTENFELDE and J.R. HANSON, J. Chem. Soo, Perkin I 1979, 1918).

However, no process for the preparation of 1-oxo or 1-hydroxy gibberellins with Δ double bond and terminal methylene group at the carbon atom 16 has hitherto been known.

Object of the invention

It is the object of the invention to provide gibberellin derivatives having modified gibberellin activity as a result of structural modification, both for practical application 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 prepare gibberellin derivatives which have an oxo or a hydroxyl group in position 1 of the ent-gibberellan skeleton and, in addition, av. are siert.

also characterized by a double bond in the Δ position.

According to the invention, gibberellin derivatives having a 1-oxo group and a 3-hydroxy group become the corresponding 1--o-Δ. gibberellin deii5 ^r and, where appropriate, then with complex Iletallhydriden to It ^ - and 1ß-

P reduced hydroxy-gibberellins.

Exemplary gibberellin derivatives useful as starting materials are those having 3-hydroxy-1-oxo-20-nor-1 9 - * - 1 O-lactone structural feature, et al. 1-oxo-gibberellin A-, 1-oxo-x, 3-eudogibberellin A derivatives derived therefrom, such as O (3) -acetoxy, O (3) -tosyloxy or O (3) -mesyloxy compounds.

Particularly suitable acylating agent for the first step of the process according to the invention is acetic anhydride, optionally in an additional solvent, e.g. Pyridine, is being worked. However, the dehydration can also be carried out with dehydrating adsorbents, for example silica gel or aluminum oxide. The 1-oxo-Δ-gibberellins are already obtained in good yields when working at room temperature.

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When acetic anhydride is used as the dehydrating agent, acetylation at the tertiary hydroxyl group at C-13 optionally occurs as a side reaction. This by-product is formed only in small amounts, if one chooses short reaction times, and can be separated during the work-up without additional operation.

In order to make the biological activity as well as stability, water solubility, uptake and transport of the compounds in the plant favorable, it is expedient to reduce the keto group in position 1 with complex metal hydrides, in particular sodium borohydride.

The isolation of the new G-ibberellin compounds prepared is carried out by known methods, in particular by column chromatography on silica gel with gradient elution.

The process according to the invention makes it possible for the first time to prepare 1-oxo or 1-hydroxy-gibberellins which have both a Δ-double bond and a terminal methylene group at the carbon atom 16.

Due to their modified structure, the compounds according to the invention have an altered G-ibberellin activity. Thus, they are of interest for practical application in the field of plant growth and development regulators as well as for biochemical research.

The invention is explained in more detail by the following exemplary embodiments.

Execution at games

Example 1: .

1-oxo-flibberellin A ^ ( 4)

260 mg of 1-oxo-gibberellin A ₁ (1) are dissolved in 3 ml of absol. Pyridine with 3 ml of acetic anhydride for 1.5 hours at room temp. implemented.

After distilling off the solvent i. VAIC. the residue is bound to 600 mg of silica gel (Woelm) and chromatographed on 15 g of silica gel (fractions to 7 ml). Combination of fractions 32 and 33 eluted with benzene / ether 6: 4 v / v gives 24 mg (9 #) amorphous 5 with / c4 / -q- 66.5 ° (c = 0.316, ethanol). IR (Nujol): ->? 902 and 1660 (> C = CH ₂ ), 1703 and 1735 (carbonyl), 1780 cnr ^ (tf-Lac ton). UV (c = 0.813, methanol): X _max 350 and 254 mn, f _M 31 and 2764, respectively; ORD (c = 0.813; methanol): DU ₂₁₀ -35 740 °, DU ₂₂₉ +124000 °, a = -1 600. MS: m / e 386 (M ⁺⁾ and 385 (H "-1), NMR (100 MHz, acetone-D ^: 1.31 (s, 18-H ₃ ), 2.79 (d, J = 10 Hz, 6-H), 3.45 (d, J = 10 Hz, 5 H), 4.93 and 5.12 (17-H ₂ ), 6.04 (d, J "= 10 Hz, 2-H) and 7.14 ()) ppm (d, J = 10 Hz, 3 Further elution with benzene / ether 1: 1 and 4: 6 v / v provides in fractions 38-90 170 mg (68 #) 4, which is prepared from acetone / n-hexane in fine needles of MP. 210 ⁰ C (dec.) and βζ / ^ - 58.7 ° (c = 0.375) crystallized IR: * _v 903 and the 1665th?

X) λ ΙΠ.Ο / Λ

Qc = CH ₂ ), 1702 and 1736 (carbonyl), 1780 cm (tf-lactone).

UV (c = 0.690): L _max 350 and 254 nm, £ _M 40 and 2543, respectively.

ORD (c = 0.690): DW ₂₆₈ -44 870 °, DU ₂₂₉ + Ί19 650 °;

a = -1 645. MS: m / e 344 (M ⁺ ) and 343 (M ~~ 1).

NMR: 1.30 (s, 18-H ₃ ), 2.74 (d, J = 10Hz, 6-H), 3.41 (d, J =

10 Hz, 5-H), 4.84 and 5.18 (17-H ₂ ), 6.04 (d, J = 10 Hz, 2-H) and 7.12 (<f) (ppm) (i.e. , J = 10 Hz, 3-H).

Example 2:

_1β- and I ^ -hydroxy-ibberellin, ^ A ^ £ 6 and 7)

270 mg of 1-oxo-gibbere.llin-Ac (4) are reduced in 50 ml of methanol with 200 mg of sodium borohanate with stirring. After 30 minutes, the solution is adjusted to pH 5 with 2% acetic acid and the solvent i. Vak. largely distilled off. The residue is taken up in 40 ml of water and the solution extracted 7 times with ethyl acetate to 15 ml. The combined ethyl acetate extracts are washed with water, dried over sodium sulfate and concentrated by evaporation in vacuo. evaporated. After adsorption of the residue (255 mg) on silica gel (Woelm) to 16 g of silica gel.

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gel chromatographed (fractions to 8 ml). Elution with benzene / ether 3: 7 v / v in the pooled fractions gives 162-259 28 mg (10 #) 6, prepared from acetone / n-hexane in fine needles of mp 152-155 ⁰ C (dec.) And fa] ² ^ -62.2 ° (c = 0.225) crystallized.

Είί _av 906 and 1654 QC = CH _0), 1700 (carbonyl), 1755 (tf-Laoton), 3035 (-CH = CH-), 3089 QC = CH ₂₎ and 3390 cm "* ¹ (hydroxyl). MS: m / e 346 (M ⁺ ).:

NM pyridine-D ^: 1.30 (s, 18-H ₃ ), 2.97 (d, J = 10Hz, 6-H), 3.44 (d, J = 10Hz, 5-H), 4.38 (d, J = 3 Hz, 1-H), 4.85 and 5.49 (17-H ₂ ), 5.82 (d, J = 9 Hz, 2-H) and 6.10 ( <5) ppm (dd, J ₁ = 9 Hz, J ₂ = 3 Hz, 3-H).

Further elution with iither or ether / glacial acetic acid 98: 2 v / v yields after combining the fractions 276-334 91 mg (33 #) 7, das.aus acetone / η-hexane in fine needles of mp 141 144 ⁰ C. (Zers.) And ß &]? ^ - 35.6 ° (c = 0.278) crystallized.

IR £ _mfav 906 and 1652 ("C = CH" _{0 "} ), 1700 and 1715 (carbonyl),

max £ - λ

1759 (^ -lactone), 3030 (-CH = CH-), 3088 QC = CH ₂ ) and 3390 cm ^{-1 of} (hydroxyl) MS: m / e 346 (M ⁺ ). MSR (pyridine-D ₅ ): 1.28 (s, 18-H ₃ ), 2.84 (d, J = 10Hz, 6-H), 2.96 (d, J = 10Hz, 5-H), 4.21 (d, J = 3Hz, 1-H), 4.67 and 4.92 (17-H ₂ ), 5.82 (d, J = 9Hz, 2-H) and 5.96 (ci) ppm (dd, J ₁ = 9 Hz, J ₂ = 3 Hz, 3-H).

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Claims (5)

invention claim 1. A process for the preparation of unsaturated 1-oxygenated gibberellins, which comprises dehydrating gibberellin derivatives which have a 1-oxo group and a 3-hydroxyl group to give the corresponding I-oxo-Δ-gibberellin and optionally subsequently with 'A 2 reduced complex metal hydrides to 1o6- and 1ß-hydroxy-Δ gibberellinen. 2. The method according to item 1, characterized in that the starting materials gibberellin derivatives with 3-hydroxy-oxo-SO-nor - ^ - used s-IO-lactone structural feature. 3. Process according to items 1 and 2, characterized in that, as dehydrating agent, acetic anhydride optionally together with an additional solvent, e.g. Pyridine, used. 4. The method according to item 1 and 2, characterized in that dehydration dehydrating adsorbents, v / ie silica gel or alumina used. 5. The method according to item 1, characterized in that ο
the 1-Οχο-Λ-gibberellins reduced by Nat riuniboranat to the corresponding Ίίχί- and Iß-hydroxy-Δ-gibberellins. For this .... ^ pages formulas