DD152787A1 - PROCESS FOR PREPARING 1-OXYGENIZED GIBBERELLINE - Google Patents

Abstract

For practical use in the field of plant growth and development regulators, gibberellin derivatives having an oxo or a hydroxyl moiety in position 1 of the ent-gibberellan backbone shall be provided. According to the invention, gibberellin derivatives having a 1-azido moiety, for example those having 1-azido-20-nor-19-> lactone structural feature, in a hydrous inert organic solvent, e.g. Tetrahydrofuran or methylene chloride, irradiated with UV light and thereby converted to the corresponding 1-oxo compounds. Optionally, subsequently complex metal hydrides, in particular sodium borohydride, are used to reduce 1-hydroxy-gibberellins in a solvent which is customary for such reductions, such as methanol. The compounds according to the invention have an altered gibberellin activity due to their modified structure.

Description

• -4 ~ 223 3 84

Process for the preparation of i-oxygenated gibberellins

The invention relates to a process for the preparation of 1-oxygenated gibberellins. These are to be understood as meaning gibberellin derivatives which have an oxygen function in position 1 of the ent-gibberellan skeleton * This is either an oxo or a hydroxy! grouping "The ent-gibberellan skeleton is intact or slightly modified (z" B "seco-, homo- or nor-gibberellan) and optionally substituted in various ways,

Field of application of the invention

The compounds according to the invention have as biological growth-regulatory active substances of biological interest and practical importance for the control of gibberellin-regulated growth and development processes and for the development of new Yfechstumsregulatoren for agriculture, gardening and .Forstwirtschaft, they also serve as starting materials for the synthesis of further structure-modified Gibberellins, which are u. A. are also suitable for use in affinity chromatography.

Characteristics of known technical solutions Naturally occurring diterpenoids. with ent-Gibberellan

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Skeletons have great biological importance 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 A. and certain fluorinated species exhibit gibberellin antagonist properties.

Numerous other structurally modified gibberellins have been prepared on partial or total synthetic Y / ege and tested for their biological activity. Thus, for example, by acid-catalyzed hydration of 3-dehydrogibberellin A "with 2 N hydrochloric acid in tetrahydrofuran and subsequent reduction with sodium borohydride 1β-hydroxy-gibberellin A ^ and 1β-hydroxy-pseudo-dogibberellin A ^ were synthesized (G. ADAM and Ph. HUWG ₅ DDR patent 112 439, C 07 d, 5/06; G. ADAI ₁ I and Ph. D. HUNG, Tetrahedron Letters 1971, 3419). 1β-Hydroxy-gibberellin A. can also be obtained by reacting a 7.19-diacid formed in the partial hydrogenation of gibberellin A ~ with lactone ring opening with mr-chloroperbenzoic acid in dioxane / benzene. From the same authors, 1β-hydroxy gibberellin A. was also isolated as natural gibberellin (gibberellin A ₅₅ ) (MY MUROPUSHI, M. SUGIMOTO, K. ITOH, Έ, TAIiAHASHI, Agric. Biol. Cher. 41 *. 2179 (1979 )).

However, it has not yet been known to produce gibberellin derivatives which have a hydroxyl group both in the 1-position and the 3-position.

The preparation of some skeletally rearranged 1-oxo-gibberellin derivatives has been described (J.R. BEARDER, 0 ', MecMILLAN, C. of CARTEMI-LICHTERPELDE and J.R.

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HAFSON, J * Chem. Soc. Perkin I 1979, 1918). However, this method is not applicable to the production of 1-Qxogibberellinen with terminal methylene group on Kohlenstoffetora 16. ,

Aim of the Invention "

It is the object of the invention to provide gibberellin derivatives which as a result of a modified structure have altered gibberellin activity, both for practical use in the field of plant growth and development regulators and for research ",

Explanation of the We sens the invention

The object of the invention is to prepare novel gibberellin derivatives which have an oxo or a hydroxyl group at position 1 of the ent-gibberellan skeleton * * '

According to the invention gibberellin derivatives are irradiated with a 1-azido moiety in a water-containing inert organic solvent with UV light, thereby converted to the corresponding 1-oxo compounds and optionally subsequently reduced with complex metal hydrides to 1-hydro-oxy-gibberellinen ,

For the implementation, it is not important whether the azido group is in the 1oi or in the 1ß position in the starting materials. Gibberellin derivatives suitable as starting materials are, for example, those with 1-azido-20-nor-19-10-octaphone structural feature, and the like. a, 1β-azido-gibberellin Α, 1β-azido-pseudogibberellin A, 1cd-azido, pseudogibberellin A _1, and ₁ -azido derivatives which can be prepared from gibberellin A, gibberellin A, Q and gibberellin A ₂

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or the corresponding methyl esters.

As a solvent for pliotolysis ζ. Β. Tetrahydrofuran or methylene chloride used

In order to improve the biological activity and stability, water solubility, uptake and transport of the compounds in the plant, it is expedient, the keto group in position 1 with complex metal hydrides, insbes-ondere Hatriumboran & t, in a conventional solvent for such reductions, eg. Methanol, to reduce

The isolation of the 1-oxygenated Gibberel ·· line produced 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-gibberellins having a terminal methylene group at the carbon atom 16 and gibberellins which have both a 1e6 and a 3-position. Possess hydroxy 1 grouping ·

Due to their modified structure, the compounds prepared according to the invention have an altered gibberellin activity, which makes them of interest for practical use in the field of plant growth and development regulators as well as for biochemical research.

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

o 4

Exemplary embodiment of the present invention: i-Oxo-gjibb erellin Α .. (5,):

Example game -1:

678 mg 1ß-azido-gibberellin A ₁ (1) are dissolved in 500 ml of tetrahydrofuran for 2 hours. With UV light (A = 254 ran) irradiated "ITpch distilling off the solvent is evaporated down i _e the residue on 1.5 g silica gel (Woelm ) and chromatographed on 35 g silica gel (fractions to 5 ml), elution with benzene / ether 1: 1 v / v yields after combining the fractions 26-46 142 mg starting product 1. The fractions 47-140 give 275 mg (56 %). ₉ based on urngesetztes starting product) 5 from Sclimp. 224-227 ⁰ C. (decomposition, from acetone / n-hexane.) And / OCj ^ -49.5 ° (c = O _s 323; C ₉ H ₁ -OH). IR (nujoi): <> _ 894 (> C = CH ₂ ), 1703 and 1732 (carbonyl), 1758 (f-lactone), 3O69 C> C = CH ₂ ) and 349O cm ^-1 (broad, hydroxyl) MS: m / e 362 (m ⁺⁾ ORD (CH ₃ OH, c = 1.38). / IIJ ₃₂₃ ° -2680,

_{3 33}

+ 2500 °, a = -52. NMR (100 MHz, "acetone-Dg): 1.21 (s 18-H ₃ ), 2.78 (d, J = 10 Hz, 6-H), 2.97 (dd," J ₁ "16 Hz , J ₂ = 5.5 Hz, 2-H ₂ ), 3.49 (d, J = 10 Hz, 5-H), 4.08 (dd, J ₁ = 5.5 Hz, J ₂ = 1, 5 Hz, JcCr-E) ₉ 4.86 and 5.16 (J) ppm '(17-H ₂ ) o

Example 2:

g 1β-azido-gibberellin A ₁ (1) are irradiated in 1.20 l of methylene chloride for 3.5 hours with UV light (λ = 254 nm). After distilling off the solvent i. Vak. the residue is chromatographed in the same way as described for example 1 _o In addition to 175 mg of starting material 1, 375 mg (40 %, based on reacted starting material)

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5 "Example 3: 1- Oxo-gibberellin A .. -methyl ester (6):

Analogously to Example 1 from 1β-azido-gibberellin A 1 -methyl ester (2):

Amorphous, M ^ -48.4 ° (c = 0.239). IR: ^ _max 904 (C = CH ₂ ), 1708 and 1735 * (carbonyl), 1782 (f-lactone), 3078 (> C = CH ₂ ) and 3490 cm ^-1 "(broad, hydroxyl). MS: m / e 376 (M ⁺ and M ") ORD (c = 1.11): / MZ _325. -2780 °, · / MZ ₂₇₄ + 1930 °, a = -47« MR (60 MHz): 1.14 (β, 18-H ₃ ), 2.67 (d, J = 10 Hz, 6-H), 2.94 (dd, J ₁ = 16 Hz, J ₂ = 5.5 Hz, 2- H ₂ ), 3.59 (d, J = 10 Hz, 5-H), 3.76 (s, COOCH ₃ ), 4.18 (dd, J-, = 5.5 Hz, J ₂ = 1, 5 Hz, 3Λ-Η), 4.99 and 5.27 (ei) ppm (17-H ₂ ) Yield: 45 %

i-Oxo-pseudogibberellin A ₁ (7): Example 4

Analogously to Example T from 1β-azido-pseudogibberellin A ₁ (3):

Amorphous , ExJ ^ -26.1 ° (c = 0.345). IRj ^ _max 903 (> C = CH _? ), 1706 and 1728 (carbonyl), 1775 (f-laeton) and 3400 cm "'(broad, hydroxyl) MS: m / e 362 (M ⁺ ) ORD (c = 0.98): ^ 322 - ^166O °> / MZ ₂₇₂ + 1940 °, a '= -36, IMR (100 MHz): 1.21 (s, 18-H ₃ ), 2.68 (d _$ J = 10 Hz, 6-H), 2.75 (d, J = 10 Hz, 5-H) ', 4.00 (dd, J ₁ = 9 Hz, J ₂ = 7 Hz, 3β-H), 4.85 and 5.16 (cT) ppm (17H ₂ )

 Yield: 44%

Example 5:

Analogously to Example 1 from 1c ~ azido ~ pseudogibberellin A.

Yield: 40 %

Example 6:

1β- hydroxy-gibberellin A, (8) and d <6-H-ydroxy -gibbereline A ₁ (9): ·

270 mg of 1-oxo-gibberellin A. (5) are reduced in 60 ml of methanol with 200 mg of sodium borohanate with stirring. After 30 minutes, the solvent i. Vak. distilled to a large extent, the residue is combined with 25 ml of 20% acetic acid and the solution i. Vak. concentrated by evaporation ₀ After binding of the crude product on silica gel (v / oelm) is chromatographed on 15 g of silica gel (fractions to 7 ml).

Ether / Glacial Acetic Acid 98: 2 v / v yields 97-116 21 mg (8 %) of the Schmpe 260 ~ 263 ⁰ C (from methanol / ether) and [ocj ^ + 38.6 ° (c = '0.285) IR: ^ ^ 910 and 1665 (> C = CH _O ), 1706 and 1740 (carbonyl), 1770 φ-lactone) and 3440 cm (hydroxyl). MS: m / e 364 (M ⁺ ) or 362 (Ι / Γ-2). MIR (200 MHz, pyridine-Dc): 1.64 '(s, 18-H ₃ ), 2.81 (m, 2-H ₂ ), 3.27 (d, J = 10 Hz, 6-H) , 4.17 (d, J = 3.5 Hz, 3Λ-Η), 4.37 (d, J = 3.5 Hz, 1ct-H) _s 4.54 (d, J = 10 Hz, 5 H), 4.92 and 5.54 (S) ppm

Further elution with ether / glacial acetic acid 95: 5 v / v yields in the fractions 121 - 196 104 mg (40 %) 9 of the mp.

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147 - 150 ⁰ C (from methanol / ether) and / kj ^ + 19.2 ° (c = 0.365). IR: ^ _mov 900 (^ C = CH ₀ ), 1703 and 1716 (carbonyl), 1760 (^ -lactone) and 3400 cm (broad, hydroxyl). MS: -m / e 364 (M ⁺ ). UMR (200 MHz, pyridine-D ₅ ): 1.58 (s, 18-H ₃ ), 3.20 (d, J = 10 Hz, 6-H), 3.94 (d, J = 10 Hz, 5-H), 4.15 (t, J = 4 Hz, 3-H), 4.60 (dd, J ₁ = 10 Hz, J ₂ = 6 Hz, 1-H), 4.93 and 5, 53 (J) ppm (17H ₂ ).

Example 7:

iβ- hydroxypseudogibberellin A ₁ (10) and 10-hydroxy- pseudo gibberellin A ^ (11);

130 mg of 1-oxo-pseudogibberellin A ₁ (7) are reduced in 50 ml of methanol with 100 mg of Ue.triumbore.npt with stirring. «

After working up analogously to Example 6 and chromatography of the residue on 7 g of silica gel (Woelm) (fractions to 4 ml) with ether / glacial acetic acid 98: 2 v / v in the fractions 107 - 143 - 70 mg (54 %) amorphous with 10 faj ^ ² + 2o, 2 ° (c = 0.350) eluted. IR: ^ 900 (> C = CH _O ), 1702 and

_O ), 7

c. λ

1716 (carbonyl), 1754 (f-lactone) and 3430 cm ^-1 (broad, hydroxyl) MS: m / e 3.64 (M ⁺ ) NMR (200 MHz, pyrldin-D ₅ ): 1.72 (s, 18-H ₃ ), 3.34 (d, J = 10Hz, 6-H), 3.94 (d, J = 10Hz, 5-H), 4.43 (d, J = 3.5Hz , 1-H), 4.44 (m, 3-H), 4.93 and 5.54 (J) ppm (17-H ₂ ).

Further elution with ether / glacial acetic acid 95: 5 v / v yields after combining the fractions 189 - 256 44 mg (34 %)

amorphous 11 with £ ^ / ί! ³ + 4.9 ° (c = 0.351). IR: -? " _W _ 902

JL / III o. Ji

(> C = CH ₂ ), 1716 and 1738 (carbonyl), 1750 (f-lecton) and 3400 cm * " ¹ (hydroxyl)" MS: m / e 364 (M ⁺ ). KMR (200 MHz ₅ pyridine-D ₅ ): 1.67 (s, 18-H ₃ ), 3.06 (d, J = 10.Hz ₅ 6-H), 3.33 (d, J = 10 Hz, 5-H), 4, 21 (m, 1- and 3-H), 4.84 and 5.46 (cf) ppm

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Claims (4)

223 384 10 Invention claim 1. A process for preparing 1-oxygenated gibberellins, which comprises irradiating gibberellin derivatives with a 1-azido grouping in a water-containing inert organic solvent with UV light, thereby converting to the corresponding 1-oxo compounds and optionally subsequently reduced to 1-hydroxy-gibberellins with complex metal hydrides * 2. Method according to item 1, characterized in that gibberellin derivatives having 1-azido-20-nor-19-s = * 10-laeton structural feature are used as starting materials 3 · Method according to item 1 and 2, characterized in that .That was used as the inert organic solvent for the photolytic reaction tetrahydrofuran or methylene chloride 4 · Process according to items 1 to 3, characterized in that the 1-oxo-gibberellins are reduced to 1-hydroxy-gibberellins by means of sodium borohydride in a solvent customary for such reductions. « For this iSeite formulas