DD220027A1 - PROCESS FOR THE PREPARATION OF CHLORINE BIBELLINES - Google Patents

Abstract

It is the object of the invention to provide for the agricultural, forestry or horticultural practice and research chlorogibberellins. The object of the invention is to develop a generally applicable process which yields gibberellin derivatives with ent-16-oxo-13-chloromethyl-17-nor-8,13-epi-gibberellan structural structure in good yields and without side reactions. According to the invention, a gibberellin derivative having a 13a-hydroxy-16-methylene structural feature is reacted in an organic solvent with a nitrogen trichloride solution. 16-oxo-131-chloromethyl-gibberellins are obtained in good yields when working at room temperature.

Description

-2- 258 036 5

O ₆ (MW 380.8) calc. C: 59.93%, H: 5.56%, Cl: 9.31%, m.p. C: 60.01%, H: 5.67%, Cl: 9.23%.

MS: m / z 362- (M ⁺ -H ₂ O), 380 (M "), UV (c = 0.770, CH ₃ OH): X _m ' _ax 290 μm, eM .14. ORD (c = 0.770, CH ₃ OH): [M] ₃₂₀ - 1797 °, [M] ₂₇₄ - + Ύ280 ^ = ^ 9ΐ7ΝΜΠΐ6αΊΜΚ ^ (d, J = 7.5Hz, 6-H), 3.40 (d, J = 7.5Hz , 5-H), 3.70 (dd,

J ₁ = 15Hz, J ₂ = 12Hz, CH ₂ Cl), 4.15 (d, J = 3.5Hz, 3-H) ₍ 5.93 (dd, J ₁ = 10Hz, J ₂ = 3.5Hz, 2-H), 6.50 (δ) ppm (d, J = 10Hz, 1-H).

Example 2 Ent-Sa ^ O-Dihydroxy-ω-oxo-IS-chloromethyl - ^^ O-dinor-e ^ S-epi-gibbereil-i-en-y.iS-diacid IS- ^ IO-lactone ^ - methylesteriB):

Analog Example 1 from GA ₃ methyl ester (2): m.p. 240-43 ⁰ C (dec.), Needles from acetone / n-hexane, [a] ₀ + 38, S ° (c = 0.258,

C ₂ H ₅ OH). · 'V ..''. -, '

IR (NuJoI) _1713x 1725 (carboxyl), 1740 (5-ring ketone), 1.765i7 lactone) and 3450 cm ^-1 "(hydroxyl). MS: m / z394 (M ⁺ ) and (M"). UV

(C = 0.13; CH ₃ OH): X _max 293nm; s _M 67.ORD (C = 0.13; CH ₃ OH): [M] ₃₂₀ '-2190 °'; [M] ₂₇₀ + 7170 °, a = -94. NMR (200MHz, acetone "D ₆ ): 1.27 (s, 18-H ₃ ), 2.89 (d, J = 7Hz, 6-H), 3.30 (d, J = 7Hz, 5). H), 3.67 (dd, J ₁ = 30Hz, J ₂ = 12Hz, CH ₂ Cl), 3.75 (COOCH ₃ ), 4.12 (d, J = 4Hz, 3-H), 5.92 (dd, J ₁ = 10Hz, J ₂ = 4 Hz, 2-H), 6.48 (s) ppm (d, J = 10Hz, 1-H) · ^l ...

Compound 5 was also obtained by methylation of 4 with ethereal diazpmethane solution. All constants are identical to those of the compound synthesized according to Example 2.

Example 3 -

ent-3a, 1p-dihydroxy-16-oxo-13-chloromethyl-17,20-dinor-8,13-epi-7,19-dioic acid Gibberella-19- »10-lactone 7-methylester (6):

Analogously to Example 1 from GA _r methyl ester (3) with absolute. Benzene as solvent: mp 288-91 ⁰ C (from acetone / ri-hexane, needles);. ² + 36.4 ° (c = 0.110 in CH ₃ OH). IR (Nujol): v _max 1730 (carboxy (), 1745 (5-ring ketone), 1765 (7-lactone) and 3490 CnT ¹ (hydroxyl). MS: m / z 395 (M ⁺ - 1) and 394 (M- 2) UV (C = 0.110, CH ₃ OH): X _max 290, _ε Μ 46. ORD (c = 0.110, CH ₃ OH). [M] _320-3648 °, [M] + ₂₇₄ 5580 °, a = -92, NMR (60MHz, pyridine-D ₅ ): 1.37 (s, 18-H ₃ ), 2.99 (d, J = 7Hz), 3.32 (d, J = 7Hz, 5-H) 3.59 (COOCH ₃ ), 3.62 (dd, J ₁ = 18Hz, J ₂ = 12Hz, CH ₂ Cl), 3.97 (δ) ppm (3-H).

Ex .: 77%. ,

Formulas to the examples

O H

CH ₃ COOR OH

CH ₃ COOR

1: Δ ¹ ,

¹ Ό - 2: δ ¹ ; R = CH ₃ ι · ';.. · -V- 3: R = CH ₃

: Δ ¹ , RH

6: R = CH ₃

Claims (4)

Invention claims: 1., A process for the preparation of Chlorgibberellinen with ent-ie-oxo-IS-chloromethyl - ^ - nor -SIS-epi-gibberellan-Strukturmerkmal, characterized in that a gibberellin derivative with 13a-hydroxy-16-methylene Structural feature in an organic solvent with nitrogen trichioride solution. ^ 2. The method according to item 1, characterized in that one carries out the reaction in an absolute solvent. 3. The method according to item 1 and 2, characterized in that one uses as solvent absolute tetrahydrofuran or absolute benzene. - 4. The method according to item 1 to 3, characterized in that one carries out the reaction at room temperature. '· For this 1 page formulas. , \ The invention relates to a process for the preparation of Chlorgibberellinen with gypberellan enyp grafting feature. The A / B ring system of the ent-gibberellan backbone is intact or slightly modified (e.g., seco-, homo-or nor-dicarboxylic) 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 and for the development of new growth regulators 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 A ₁ , certain fluorinated species, and homogibberellin A ₃ exhibit gibberellin antagonistic properties. Numerous other structurally modified gibberellins have been prepared by partial or total synthetic methods and tested for their biological activity. Thus, bromination of GA ₁ and GA ₃ with pyridinium perbromide in tetrahydrofuran provides ent-3a, 10-dihydroxy-16-oxo-13-bromomethyl · 17,20-dinor-8,13-epi-gibberella-7,1-diacid-19 - ^ 10-lactone or the corresponding Δ ¹ -compound (N.TAKAHASHI, Y.SETA / H.KITÄMURA, Y.SUMIKI, Bull, agric., Chem. Soc., Japan 23, 509 (1959); AISCOTT, F. McCAPRA, F.COMER, SASUTHERLAND, DWYOUNG, GASIM, A.FERGUSON, Tetrahedron [London] 2fi, 1339 (1964)). In addition, starting from gibberellin A ^ methyl ester, by reaction with tert-butyl hypochlorite, the corresponding / 3-chloroketone (see 6 in the formula scheme) was obtained (DC ALDRIDGE, JF GROVE, RN SPEAKE, BK TIDD, W. KLYNE, J. Chem Soc. 1963 , 143). However, this process gives at most 41% yield and, when applied to the GA ₃ series, results in a product mixture in which the proportion of the 16-oxo-13-chloromethyl compound is still substantially lower. Object of the invention ^l It is the object of the invention to provide chlorogibberellins 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 develop a generally applicable process which leads in good yields and without side reactions to Gibbereilin derivatives with ent-ie-oxo-IS-chloromethyl-i-nor-S ^ S-epi-gibberellan structural feature , According to the invention, a gibberellin derivative having an ISa-hydroxy-1-methylene structural feature in an organic solvent, preferably in an absolute solvent, is reacted with a nitrogen trichloride solution to give a chlorogibberellin having ent-ie-oxo-IS-chloromethyl-IV-nor-SjiS implemented epi-gibberellan structural feature. Suitable starting compounds are, for example, gibberellins of the A ₃ and A _r series or their methyl esters. The nitrogen trichloride is used dissolved either in absolute benzene or in absolute carbon tetrachloride (S.A.W.A. NOYES, Inorg., Syntheses, 1.65 (1939)). , A wide variety of organic solvents can be used for the process according to the invention, for example hexane, benzene, methylene chloride, carbon tetrachloride or tetrahydrofuran. le-oxo-IS-chloromethyl-gibberellins are obtained in good yields when the reaction is carried out at room temperature performs. '....'. '- The isolation of the produced chlorogibberellins is carried out by known methods. After distilling off the solvent is crystallized or optionally purified by chromatography. The process according to the invention makes it possible in good yields to introduce a chloromethyl grouping at C-13 while retaining the structural features in the Α-ring of the ent-gibberellan skeleton, so it is generally applicable. By-products are not formed. The chlorogibberellins which can be prepared according to the invention with lo-oxo-iS-chloromethyl structural features are novel, but only compound 6 (see formulae) is already known. They have altered gibberellin activity due to their modified structure. 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: embodiments Example 1 / ent-3a, 10-dihydroxy-16-oxo-13-chloromethyl-17,20-dinor-8,13-epi-gibberell-1-ene-7,19-dioic acid-19 ^ 10-lactone (4): 1.0 g of GA ₃ (D) are reacted in 10 mol of absolute tetrahydrofuran with a 6% solution of nitrogen trichloride in benzene at room temperature for 30 min After evaporation of the solution in vacuo, the residue is chromatographed on 50 g of SiO ₂ (frit to 25 ml ) eluting with ether / glacial acetic acid 98: 2v / v delivers to evaporation of the Frktn 47-72 934mg (84%) 4 which from acetone / n-hexane in needles, mp 278-282 ⁰ C (dec), and... [a] j§ ³ + 33.3 ° (c = 0.409, ethanol) IR (KBr): fi _rri ^: _ax T73Ö (Caryboxyl L 1740 (5-ring ketone), 1770 (y-lactone) and 3450cm " ¹ (hydroxyl).