Patent Application: US-201314403132-A

Abstract:
a compound of general formula : in which x represents o , s , nh or an n - alkyl radical , r 1 and r 2 , identical or different , each represent h or a c 1 - c 10 hydrocarbon radical , r 1 and r 2 not both representing h , r 3 represents a c 1 - c 10 hydrocarbon radical , and r represents a phenyl radical monosubstituted or disubstituted by a substituent y and , if applicable , a substituent z , chosen from cl , br , i and cf 3 , or r represents a c ═ r 4 radical in which r 4 represents an hydrocarbon radical and r 5 represents a linear or branched , saturated or unsaturated , hydrocarbon radical , optionally substituted , a cor 6 group or a co 2 r 6 group , where r 6 represents a hydrogen atom or a linear or branched , saturated or unsaturated , hydrocarbon radical . this compound can be used for the treatment of higher plants for controlling their growth and architecture .

Description:
the infrared spectra were recorded in a film on a diamond window . the data are given in cm − 1 ( ν , cm − 1 ). the 1 h and 13 c nmr spectra were recorded on solutions in cdcl 3 , using the protic solvent c h cl 3 ( δ h = 7 . 24 ppm ) or c dcl 3 ( δ c = 77 . 23 ppm ) as internal reference and are given in ppm . all the reactions were monitored by thin layer chromatography ( tlc ) on 0 . 2 mm aluminum plates precoated with silica gel , using uv light and an ethanolic solution containing 5 % of phosphomolybdic acid , and heat as developing agent . flash chromatography was carried out on silica gel 60 , 40 - 63 μm ( 400 - 230 mesh ), with ethyl acetate ( etoac ) and heptane as eluents . the commercially available reagents and solvents were purified and dried when necessary using conventional methods . dimethylformamide dmf and dichloromethane ch 2 cl 2 were dried by distillation over calcium hydride , acetate was dried by distillation over anhydrous caso 4 . unless otherwise indicated , all the other reagents were obtained from commercial sources and used without further purification . was synthesized from 4 - chlorothiophenol and from 5 - chloro - 3 , 4 - dimethylfuran - 2 ( 5h )- one , according to the following reaction scheme : a solution of 5 - chloro - 3 , 4 - dimethylfuran - 2 ( 5h )- one ( 405 mg , 2 . 6 mmol ) ( prepared according to the method of canevet et al ., 1978 ) in anhydrous acetone ( 5 ml ) is added to a solution of commercial 4 - chlorothiophenol ( 400 mg , 2 . 76 mmol ) in anhydrous acetone ( 10 ml ) with anhydrous k 2 co 3 ( 459 mg , 3 . 31 mmol ), placed at ambient temperature under argon . the progression of the reaction is monitored by tlc ( sio 2 ; 8 : 2 heptane / etoac ). after stirring for 1 day , the acetone is evaporated off . the crude is purified by silica chromatography ( eluent 8 : 2 heptane / etoac ) to give the compound ( iia ) in the form of a white solid ( 361 mg , 1 . 42 mmol , 51 %). 1 h nmr ( 300 mhz , cdcl 3 ): δ 7 . 34 ( dt , j = 8 . 7 , 2 . 1 hz , 2h ), 7 . 20 ( dt , j = 8 . 7 , 2 . 1 hz , 2h ), 5 . 83 - 5 . 82 ( m , 1h ), 1 . 96 ( t , j = 1 . 0 hz , 3h ), 1 . 64 ( t , j = 1 . 0 hz , 3h ). 13 c nmr ( 75 mhz , cdcl 3 ): δ 172 . 6 ( c ), 155 . 2 ( c ), 135 . 4 ( c ), 135 . 2 ( 2ch ), 129 . 2 ( 2ch ), 128 . 2 ( c ), 126 . 2 ( c ), 88 . 1 ( ch ), 12 . 6 ( ch 3 ), 8 . 5 ( ch 3 ). ir ν max ( film ): 2924 , 1758 , 1673 , 1476 , 1093 , 985 cm − 1 . hrms ( esi ): m / z calculated for c 12 h 12 clo 2 s [ m + h ] + : 255 . 0247 . found : 255 . 0245 . was synthesized from 4 - bromothiophenol and from 5 - chloro - 3 , 4 - dimethylfuran - 2 ( 5h )- one , according to a reaction scheme similar to that indicated above for the compound ( iia ), in the following way . a solution of 5 - chloro - 3 , 4 - dimethylfuran - 2 ( 5h )- one ( 263 . 8 mg , 1 . 8 mmol ) in anhydrous acetone ( 10 ml ) is added to a solution of commercial 4 - bromothiophenol ( 283 . 6 mg , 1 . 5 mmol ) in anhydrous acetone ( 15 ml ) with anhydrous k 2 co 3 ( 337 mg , 3 mmol , 3 eq . ), placed at ambient temperature under argon . the progression of the reaction is monitored by tlc ( sio 2 ; 8 : 2 heptane / etoac ). after stirring for 8 days , the acetone is evaporated off and the residue is taken up with ch 2 cl 2 so as to be filtered through celite . after evaporation , the resulting brown solid is purified by silica chromatography ( introduction and elution with ch 2 cl 2 , silica column 2 cm in diameter and 45 cm in height ) to give the compound ( iib ) in the form of a transparent solid ( 152 . 4 mg , 0 . 51 mmol , 34 % yield ). 1 h nmr ( cdcl 3 , 500 mhz ): δ ( ppm ) 1 . 71 ( broad s , 3h ), 2 . 03 ( broad s , 3h ), 5 . 89 ( broad s , 1h ), 7 . 38 ( d , j = 8 . 2 hz , 2h ), 7 . 46 ( d , j = 8 . 2 hz , 2h ). 13 c nmr ( cdcl 3 , 125 . 5 mhz ): δ ( ppm ) 8 . 7 ( ch 3 ), 12 . 8 ( ch 3 ), 88 . 2 ( ch ), 123 . 8 ( c ), 126 . 6 ( c ), 129 . 0 ( c ), 132 . 4 ( 2ch ), 135 . 5 ( 2ch ), 155 . 1 ( c ), 172 . 7 ( c ). ir ν max ( film ): 1760 , 1686 , 1673 cm − 1 . hrms ( esi ): m / z calculated for c 12 h 10 o 2 sbr [ m − h ] − : 296 . 9585 . found : 296 . 9592 . was synthesized from 4 -( trifluoromethyl ) thiophenol and 5 - chloro - 3 , 4 - dimethylfuran - 2 ( 5h )- one , according to a reaction scheme similar to that indicated above for the compound ( iia ), in the following way . a solution of 5 - chloro - 3 , 4 - dimethylfuran - 2 ( 5h )- one ( 263 . 8 mg , 1 . 8 mmol ) in anhydrous acetone ( 10 ml ) is added to a solution of commercial 4 -( trifluoromethyl ) thiophenol ( 267 . 3 mg , 1 . 5 mmol ) in anhydrous acetone ( 15 ml ) with anhydrous k 2 co 3 ( 337 mg , 3 mmol , 3 eq . ), placed at ambient temperature under argon . the progression of the reaction is monitored by tlc ( sio 2 ; 8 : 2 heptane / etoac ). after stirring for 8 days , the acetone is evaporated off and the residue is taken up with ch 2 cl 2 so as to be filtered through celite . after evaporation , the resulting brown oil is purified twice by silica chromatography ( introduction and elution with ch 2 cl 2 , silica column 2 cm in diameter and 45 cm in height ) to give the compound ( iic ) in the form of a transparent pale yellow oil ( 112 . 8 mg , 0 . 39 mmol , 26 % yield ). 1 h nmr ( cdcl 3 , 500 mhz ): δ ( ppm ) 1 . 75 ( broad s , 3h ), 2 . 06 ( broad s , 3h ), 5 . 99 ( broad s , 1h ), 7 . 57 ( d , j = 8 . 6 hz , 2h ), 7 . 63 ( d , j = 8 . 6 hz , 2h ). 13 c nmr ( cdcl 3 , 125 . 5 mhz ): δ ( ppm ) 8 . 7 ( ch 3 ), 12 . 8 ( ch 3 ), 88 . 0 ( ch ), 122 . 1 ( c ), 125 . 7 ( cf 3 ), 126 . 0 ( ch ), 126 . 1 ( ch ), 126 . 8 ( ch ), 132 . 8 ( 2ch ), 135 . 9 ( c ), 154 . 8 ( c ), 172 . 6 ( c ). ir ν max ( film ): 1766 , 1687 , 1672 cm − 1 . hrms ( esi ): m / z calculated for c 13 h 10 o 2 f 3 s [ m − h ] − : 287 . 0354 . found : 287 . 0342 . was synthesized from 4 - chlorophenol and 5 - chloro - 3 , 4 - dimethylfuran - 2 ( 5h )- one , according to a reaction scheme similar to that indicated above for the compound ( iia ), in the following way . a solution of 5 - chloro - 3 , 4 - dimethylfuran - 2 ( 5h )- one ( 1 . 45 g , 9 . 89 mmol ) ( prepared according to the method of canevet et al ., 1978 ) in anhydrous acetone ( 20 ml ) was added to a solution of commercial 4 - chlorophenol ( 0 . 847 g , 6 . 59 mmol ) in anhydrous acetone ( 50 ml ) with anhydrous k 2 co 3 ( 1 . 821 g , 13 . 13 mmol ), placed at ambient temperature under argon . the progression of the reaction is monitored by tlc ( sio 2 ; 8 : 2 heptane / etoac ). after stirring for 2 days , the acetone is evaporated off . the crude is purified by silica chromatography ( eluent 8 : 2 heptane / etoac ) then recrystallized ( hexane / etoac ) to give the compound ( ii ′ d ) in the form of a white solid ( 793 mg , 3 . 33 mmol , 50 %). 1 h nmr ( 300 mhz , cdcl 3 ): δ 7 . 27 ( dt , j = 9 . 0 , 3 . 2 hz , 2h ), 7 . 06 ( dt , j = 9 . 0 , 3 . 0 hz , 2h ), 6 . 00 - 5 . 99 ( broad s , 1h ), 2 . 05 ( t , j = 1 . 0 hz , 3h ), 1 . 87 ( t , j = 1 . 0 hz , 3h ). 13 c nmr ( 75 mhz , cdcl 3 ): δ 171 . 8 ( c ), 155 . 5 ( c ), 153 . 6 ( c ), 129 . 8 ( 2ch ), 128 . 9 ( c ), 127 . 4 ( c ), 118 . 5 ( 2ch ), 100 . 9 ( ch ), 11 . 8 ( ch 3 ), 8 . 7 ( ch 3 ). ir ν max ( film ): 1773 , 1694 , 1490 , 1227 , 974 cm − 1 . ms ( es − ): m / z (%) 237 . 0 ( 100 %, [ m − h ] − ), 273 . 0 ( 90 %, [ m + cl ] − ). hrms ( esi ): m / z calculated for c 12 h 10 clo 3 [ m − h ] − : 237 . 0318 . found : 237 . 0325 . was synthesized from 4 - bromophenol and 5 - chloro - 3 , 4 - dimethylfuran - 2 ( 5h )- one , according to a reaction scheme similar to that indicated above for the compound ( iia ), in the following way . a solution of 5 - chloro - 3 , 4 - dimethylfuran - 2 ( 5h )- one ( 245 . 0 mg , 1 . 67 mmol ) in anhydrous acetone ( 10 ml ) is added to a solution of commercial 4 - bromophenol ( 259 . 5 mg , 1 . 5 mmol ) in anhydrous acetone ( 15 ml ) with anhydrous k 2 co 3 ( 337 mg , 3 mmol , 3 eq . ), placed at ambient temperature under argon . the progression of the reaction is monitored by tlc ( sio 2 ; 8 : 2 heptane / etoac ). after stirring for 17 days , the acetone is evaporated off and the residue is taken up with ch 2 cl 2 so as to be filtered through celite . after evaporation , the resulting brown solid is purified by silica chromatography ( introduction and elution with ch 2 cl 2 , silica column 2 cm in diameter and 45 cm in height ) to give the compound ( ii ′ e ) in the form of a transparent solid ( 241 . 7 mg , 0 . 85 mmol , 57 % yield ). 1 h nmr ( cdcl 3 , 500 mhz ): δ ( ppm ) 1 . 89 ( broad s , 3h ), 2 . 07 ( broad s , 3h ), 6 . 02 ( broad s , 1h ), 7 . 03 ( d , j = 9 . 0 hz , 2h ), 7 . 43 ( d , j = 9 . 0 hz , 2h ). 13 c nmr ( cdcl 3 , 125 . 5 mhz ): δ ( ppm ) 8 . 7 ( ch 3 ), 11 . 7 ( ch 3 ), 100 . 8 ( ch ), 116 . 3 ( c ), 118 . 9 ( 2ch ), 127 . 3 ( c ), 132 . 8 ( 2ch ), 153 . 5 ( c ), 156 . 0 ( c ), 171 . 7 ( c ). hrms : m / z ( 280 . 9809 , [ m − h ] − ); calculated for c 12 h 10 o 3 br : 280 . 9813 . was synthesized from 4 -( trifluoromethyl ) phenol and 5 - chloro - 3 , 4 - dimethylfuran - 2 ( 5h )- one , according to a reaction scheme similar to that indicated above for the compound ( iia ), in the following way . a solution of 5 - chloro - 3 , 4 - dimethylfuran - 2 ( 5h )- one ( 263 . 4 mg , 1 . 8 mmol ) in anhydrous acetone ( 10 ml ) is added to a solution of commercial 4 -( trifluoromethyl ) phenol ( 243 . 2 mg , 1 . 5 mmol ) in anhydrous acetone ( 15 ml ) with anhydrous k 2 co 3 ( 337 mg , 3 mmol , 3 eq . ), placed at ambient temperature under argon . the progression of the reaction is monitored by tlc ( sio 2 ; 8 : 2 heptane / etoac ). after stirring for 8 days , the acetone is evaporated off and the residue is taken up with ch 2 cl 2 so as to be filtered through celite . after evaporation , the resulting brown solid is purified by silica chromatography ( introduction and elution with ch 2 cl 2 , silica column 2 cm in diameter and 45 cm in height ) to give the compound ( ii ′ f ) ( 132 . 2 mg , 32 %) in the form of a transparent solid . 1 h nmr ( cdcl 3 , 500 mhz ): δ ( ppm ) 1 . 91 ( broad s , 3h ), 2 . 09 ( broad s , 3h ), 6 . 12 ( broad s , 1h ), 7 . 22 ( d , j = 8 . 6 hz , 2h ), 7 . 61 ( d , j = 8 . 6 hz , 2h ). 13 c nmr ( cdcl 3 , 125 . 5 mhz ): δ ( ppm ) 8 . 7 ( ch 3 ), 11 . 7 ( ch 3 ), 100 . 1 ( ch ), 116 . 9 ( 2ch ), 122 . 4 ( c ), 126 . 0 ( cf 3 ), 127 . 3 ( 2ch ), 127 . 4 ( c ), 153 . 4 ( c ), 159 . 2 ( c ), 171 . 6 ( c ). hrms : m / z ( 271 . 0579 , [ m − h ] − ); calculated for c 13 h 10 o 3 f 3 : 271 . 0582 . was synthesized from 7 - hydroxycoumarin and 5 - chloro - 3 , 4 - dimethylfuran - 2 ( 5h )- one , according to the following reaction scheme : solid 7 - hydroxycoumarin , which is commercially available or readily accessible according to the method of timonen et al . ( 2011 ) ( cas rn : 93 - 35 - 6 , 300 mg , 1 . 85 mmol ), is added to a solution of 5 - chloro - 3 , 4 - dimethylfuran - 2 ( 5h )- one ( 352 mg , 2 mmol ) ( prepared according to the method of cavenet et al . ( 1978 )) in anhydrous acetonitrile ( 10 ml ), placed at ambient temperature under argon . n , n - diisopropylethylamine is then added ( 697 μl , 4 mmol ). the progression of the reaction is monitored by tlc ( sio 2 ; 1 : 1 heptane / etoac ). after stirring for 12 h , the acetonitrile is evaporated off . the crude is purified by silica chromatography ( eluent 6 : 4 heptane / etoac ) to give the compound ( ii ″ g ) in the form of a white solid ( 423 mg , 1 . 55 mmol , yield : 84 %). 1 h nmr ( 300 mhz , cdcl 3 ): δ 1 . 85 ( t , j = 1 . 2 hz , 3h ), 2 . 04 ( t , j = 0 . 9 hz , 3h ), 6 . 08 ( s , 1h ), 6 . 24 - 6 . 27 ( d , j = 9 . 5 hz , 1h ), 6 . 98 - 7 . 01 ( m , 2h ), 7 . 37 - 7 . 39 ( d , j = 8 . 1 hz , 1h ), 7 . 58 - 7 . 61 ( d , j = 9 . 6 hz , 1h ). 13 c nmr ( 75 mhz , cdcl 3 ): δ 8 . 7 ( ch 3 ), 11 . 7 ( ch 3 ), 99 . 9 ( ch ), 104 . 6 ( ch ), 113 . 5 ( ch ), 114 . 8 ( ch ), 114 . 9 ( ch ), 127 . 5 ( c ), 129 . 3 ( ch ), 143 . 1 ( ch ), 153 . 3 ( c ), 155 . 5 ( c ), 159 . 5 ( c ), 160 . 7 ( c ), 171 . 4 ( c ). ir ν max ( film ): 661 , 750 , 834 , 886 , 975 , 1052 , 1088 , 1131 , 1162 , 1195 , 1236 , 1285 , 1318 , 1361 , 1387 , 1505 , 1565 , 1615 , 1624 , 1689 , 1745 , 1781 , 3081 cm − 1 . hrms ( esi ): m / z calculated for c 15 h 13 o 5 [ m + h ] + : 273 . 0718 . found : 273 . 0753 . was synthesized from the sodium salt of methylmalondialdehyde and 5 - chloro - 3 , 4 - dimethylfuran - 2 ( 5h )- one , according to the reaction scheme below : for this , the sodium salt of methylmalondialdehyde ( obtained in accordance with the publication by nair et al ., 1981 ) ( 244 mg , 2 . 6 mmol ), 5 - chloro - 3 , 4 - dimethylfuran - 2 ( 5h )- one ( 165 mg , 1 . 13 mmol ) and dimethyl sulfoxide ( 2 ml ) are mixed and stirred at ambient temperature for 14 h . the completion of the reaction is verified by tlc ( heptane / etoac , 8 / 2 v / v ). water is then added to the mixture until complete dissolution of the salts , then the aqueous phase is extracted 3 times with dichloromethane . the combined organic phases are dried with na 2 so 4 , filtered and evaporated under reduced pressure until a dry residue is obtained . the crude product is purified by silica gel chromatography with a linear gradient of 0 - 50 % v / v of etoac in heptane , so as to obtain the desired compound ( iiia ) ( 202 mg , 1 . 03 mmol , yield 91 %) in the form of a white solid . 1 h nmr ( 500 mhz , cdcl 3 ): δ : 9 . 36 ( s , 1h ), 7 . 18 ( s , 1h ), 6 . 01 ( s , 1h ), 2 . 08 ( s , 3h ), 1 . 94 ( s , 3h ), 1 . 73 ( s , 3h ). 13 c nmr ( 125 mhz , cdcl 3 ) δ : 191 . 5 ( ch ), 170 . 9 ( c ), 161 . 4 ( ch ), 152 . 6 ( c ), 128 . 2 ( c ) 123 . 3 ( c ), 101 . 8 ( ch ), 11 . 4 ( ch 3 ), 8 . 8 ( ch 3 ), 6 . 6 ( ch 3 ) ir ν max ( film ): 1771 , 1684 , 1652 , 1168 , 978 cm − 1 . hrms ( esi , positive mode ): calculated for c 10 h 13 o 4 [ m + h + ]: 197 . 0814 . found : 197 . 0809 . is synthesized from the compound ( iiia ) above , according to the reaction scheme below : the compound ( iiia ) ( 100 mg , 0 . 5 mmol ) is dissolved in dry toluene ( 10 ml ). commercially available methyl ( triphenylphosphoranylidene ) acetate ( 203 mg , 0 . 61 mmol ) is added and the resulting mixture is stirred at reflux for 12 h . the completion of the reaction is verified by tlc ( heptane / etoac , 7 : 3 , v / v ). the reaction mixture is then concentrated under reduced pressure and the residue is purified by chromatography on a column of silica gel with a linear gradient of etoac ( 0 - 20 %) in heptane as mobile phase , so as to obtain the desired dienoate ( iiib ) in the form of a white powder ( 77 mg , 305 μmol , yield = 80 % after elimination of the unreacted starting aldehyde ( iiia )). 1 h nmr ( 500 mhz , cdcl 3 ) δ : 7 . 23 ( d , j = 15 . 4 hz , 1h ), 6 . 69 ( s , 1h ), 5 . 85 ( s , 1h ), 5 . 79 ( d , j = 15 . 4 hz , 1h ), 3 . 72 ( s , 3h ), 1 . 99 ( s , 3h ), 1 . 87 ( s , 3h ), 1 . 73 ( s , 3h ). 13 c nmr ( 125 mhz , cdcl 3 ) δ : 171 . 2 , 167 . 7 , 153 . 0 , 148 . 3 , 144 . 9 , 127 . 8 , 117 . 4 , 115 . 1 , 101 . 6 , 51 . 5 , 11 . 4 , 9 . 4 , 8 . 6 . ir ν max ( film , cm − 1 ): 1767 , 1718 , 1639 , 1317 , 1154 , 979 . hrms ( esi , positive mode ): m / z = 253 . 1076 [ m + h ], calculated for c 13 h 17 o 5 = 253 . 1031 . is synthesized from the compound ( iiia ) above , according to the reaction scheme below : methyltriphenylphosphonium bromide ( 1 . 25 g , 3 . 5 mmol ) is dissolved in dry thf ( 4 ml ) and cooled to − 50 ° c . butyllithium ( 2 . 25 ml , 3 . 6 mmol , 1 . 6 m in hexane ) is added dropwise and the resulting mixture is heated to − 10 ° c . over the course of 45 min , and cooled to − 78 ° c . a solution of ( iiia ) ( 400 mg , 2 . 04 mmol ) in thf ( 4 ml ) is added dropwise and the mixture is stirred for 2 h 30 at − 50 ° c . the reaction mixture is then left to heat back up to − 20 ° c . before being poured into a mixture of ch 2 cl 2 and phosphate buffer ( ph 7 ) ( v / v ; 1 / 1 ). the mixture is extracted 3 times with ch 2 cl 2 , the combined organic phases are washed with water and dried under reduced pressure , and the resulting residue is purified by chromatography on a column of silica gel with a linear gradient of etoac ( 0 - 50 %) in heptane as mobile phase , so as to obtain the desired diene ( iiic ) in the form of a pale yellow oil ( 150 mg , 773 μmol , yield = 38 %). 1 h nmr ( 500 mhz , cdcl 3 ) δ : 6 . 34 ( s , 1h ), 6 . 69 ( s , 1h ), 6 . 22 ( dd , j = 17 . 2 , 10 . 7 hz , 1h ), 5 . 77 ( s , 1h ), 5 . 08 ( d , j = 17 . 2 hz , 1h ), 4 . 94 ( d , j = 10 . 7 hz , 1h ), 1 . 98 ( s , 3h ), 1 . 85 ( s , 3h ), 1 . 71 ( s , 3h ). 13 c nmr ( 125 mhz , cdcl 3 ) δ : 171 . 6 , 154 . 2 , 142 . 4 , 135 . 5 , 127 . 4 , 119 . 2 , 111 . 0 , 101 . 8 , 11 . 4 , 9 . 04 , 8 . 4 . ir ν max ( film , cm − 1 ): 1766 , 1150 , 960 . hrms ( esi , positive mode ): m / z = 195 . 1020 [ m + h ] + , calculated for c 11 h 15 o 3 = 195 . 1021 . gr24 was prepared according to the method known per se described in mangnus et al ., 1992 . gr5 was synthesized according to the method known per se described in johnson et al ., 1981 . which differs from the compounds according to the invention , in particular from the compounds corresponding to formula ( iii ), in that r 1 and r 2 both represent a hydrogen atom , is prepared according to the protocol described in patent document wo 2010 / 137662 . the comparative compounds comp . 4 , comp . 5 and comp . 6 , of respective general formulae : which differ from the compounds according to the invention , in particular from the compounds corresponding to formula ( ii ′), in that r 1 and r 2 both represent a hydrogen atom , are prepared according to the protocols described in patent document wo 2012 / 043813 and in the publication by fukui et al . ( 2011 ). the stability in aqueous medium of the compound ( iia ) according to the invention and that of gr24 as comparative compound was evaluated in the following way . each compound was diluted in acetone ( 1 ml ), then 50 μl of each solution were diluted with methanol ( 175 μl ) and water ( 750 μl ) so as to obtain a compound concentration of 50 μg / ml . the aqueous solution thus obtained was incubated at 21 ° c . in hplc vials . indanol ( 25 μl of a solution at 1 mg / ml in acetone ) was added to each solution in order to serve as an internal standard . the degradation of each compound over time was monitored by analysis of samples taken from the solution at various time intervals , by ultra performance liquid chromatograpy ( uplc ) by means of an acquity uplc hss c 18 column ( 1 . 8 μm , 2 . 1 × 50 mm ), eluted first of all with a solution of acetonitrile at 5 % in water containing 0 . 1 % of formic acid , for 0 . 5 min , then with a gradient of 5 % to 100 % of acetonitrile in water containing 0 . 1 % of formic acid , for 6 . 5 min , and with 100 % of acetonitrile containing 0 . 1 % of formic acid for 3 min . the column was maintained at a temperature of 40 ° c ., with a flow of 0 . 6 ml / min . the compounds eluted from the column were detected with a photodiode array detector . the relative amount of nondegraded compound in the solution was determined by comparison with the internal standard . the results obtained are shown on the curve of fig1 , as % of nondegraded compound in the solution as a function of incubation time . it is clearly observed thereon that the compound ( iia ) exhibits a very high chemical stability in aqueous solution , much higher than that of gr24 . in a second experiment , the stability in aqueous medium of the compounds ( iia ) and ( iiib ) according to the invention , and that of gr24 as comparative compound , was evaluated according to the protocol described above . the results obtained are shown in fig2 , as % of nondegraded compound in the solution , as a function of incubation time . the results obtained , including over longer incubation times , confirm that the compound ( iia ) exhibits a very high chemical stability in aqueous solution , much higher than that of gr24 . the stability in aqueous medium of the compound ( iiib ) is also even better than that of the compound ( iia ). the cytotoxicity of the compound ( iia ) according to the invention , and that of gr24 and of gr5 as comparative compounds , was evaluated in vitro , at concentrations of 10 − 4 m and 10 − 5 m , on mrc5 cells , in dmso , in the following way . mrc5 cells ( human lung ( fibroblasts ) were cultured in dulbecco &# 39 ; s modified eagle medium ( dmem ) supplemented with : 25 mm of glucose , 10 % ( v / v ) of fetal calf serum , 100 iu of penicillin , 100 μg / ml of streptomycin and 1 . 5 μg / ml of fungizone , and kept under 5 % of co 2 at 37 ° c . 96 - well plates were seeded with 2100 mrc5 cells per well in 200 μl of medium . after 24 hours , each of the compounds dissolved in dmso was added for 72 hours , at a final concentration of 10 − 4 m or 10 − 5 m in a fixed volume of dmso . the controls received an equal volume of dmso . the viable cell number was measured at 490 nm with the mts reagent ( promega ), and , for each compound , the concentration causing 50 % inhibition of cell growth , ic 50 , was calculated . the results , in terms of percentage inhibition of cell growth (± standard error ), are shown in table 1 below . the above results clearly show that , at the concentration of 10 − 4 m , the compound in accordance with the invention ( iia ) exhibits a cytotoxicity which is much lower than that of the comparative compounds gr5 and gr24 . to this effect , ramosus ( rms1 ) hyperbranched pea ( pisum sativum l .) mutants , known to exhibit a number of branches very much higher than the number of branches in wild - type pea , and in particular at all the nodes of the plant , were used . generally , in the pea , the first two scales are considered to be the first two nodes , the cotyledonary node being node 0 . the rms1 mutant is an “ sms ” signal biosynthesis mutant , repressing branching of the plant . tests for activity on the inhibition of branching were carried out in the following way . the strigolactone - deficient rms1 ( ccd8 ) pea mutants described in beveridge et al ., 1997 , were used for the test ( m3t884 line derived from the térèse variety ). the activity of the compounds ( iia ), ( ii ′ d ) and ( ii ′ e ) in accordance with the invention and of the comparative compound gr24 was evaluated at respective doses of 10 nm , 100 nm and 1 μm , by treatment at node 3 . for this , solutions containing each compound to be tested in 1 % acetone , 4 % polyethylene glycol 1450 and 50 % ethanol were used . 24 plants were sown per treatment . 8 days after sowing , the treatment was carried out on the axillary bud at node 3 , by application of 10 μl of each solution to be tested , directly on the bud , by means of a micropipette . the lateral outgrowths at nodes 1 and 2 were removed in order to encourage the growth of the axillary buds at the higher nodes . the sprouting of the axillary buds at node 3 was measured 8 days after the treatment , by means of a digital sliding caliper . the results , expressed as length of bud / branch 8 days after treatment with each compound , for each concentration tested , are shown in fig3 . the control without treatment ( 0 nm ) is also represented in this figure . it is observed therein that the compound ( iia ) exhibits , at the highest concentrations , an inhibitory activity on bud growth which is greater than that of the comparative compound gr24 . the compounds ( ii ′ d ) and ( ii ′ e ) also exhibit an inhibitory activity on bud growth at node 3 , at the concentration of 1 μm . the activity of the compounds ( iia ), ( iib ), ( iic ), ( ii ′ d ), ( ii ′ e ) and ( ii ′ f ) in accordance with the invention was evaluated at respective doses of 100 nm and 1 μm , by treatment at node 3 . for this , solutions containing each compound to be tested , in 1 % acetone , 4 % propylene glycol 1450 and 50 % ethanol , were used . 24 plants were sown per treatment . 8 days after sowing , the treatment was carried out on the axillary bud at node 3 , by application of 10 μl of each solution to be tested , directly on the bud , by means of a micropipette . the lateral outgrowths at nodes 1 and 2 were removed in order to encourage the growth of the axillary buds at the higher nodes . the sprouting of the axillary buds at node 3 was measured 8 days after the treatment , by means of a digital sliding caliper . the results , expressed as length of bud / branch 8 days after treatment with each compound , for each concentration tested , are shown in fig4 . the control without treatment ( 0 nm ) is also represented in this figure . it is observed therein that all the compounds in accordance with the invention exhibit an inhibitory activity on bud growth at node 3 . the compounds comprising a sulfur atom in the molecular ( compounds ( iia ), ( iib ) and ( iic )) prove to be the most active . the activity of the compounds ( iia ), ( iiia ), ( iiib ) and ( iiic ) in accordance with the invention , and also of gr24 as comparative compound , was evaluated at respective doses of 100 nm and 1 μm , by treatment at node 3 , according to the protocol described above with reference to experiment 2 . a sample consisting only of the solvent , and without active compound , was also tested as negative control , termed “ ctl 0 ”. the results , expressed in length of bud / branch 8 days after treatment with each compound , for each concentration tested , are shown in fig5 . it is observed that the compounds ( iia ) and ( iiib ) in accordance with the invention exhibit an activity similar to that of the comparative compound gr24 . the compounds ( iiia ) and ( iiic ), although slightly less active , exhibit , however , a high activity in terms of bud growth inhibition . in this experiment , the activity of the compound ( iiia ) in accordance with the invention , and also of gr24 as comparative compound , was evaluated at respective doses of 1 nm , 10 nm , 100 nm and 1 μm , by treatment at node 3 , according to the protocol described above with reference to experiment 2 , for doses of 10 nm , 100 nm and 1 μm of compounds . a sample consisting only of the solvent , and without active compound (“ ctl 0 ”) was also tested as a negative control . a nontreated (“ nt ”) control was also carried out . the results , expressed as length of bud / branch 8 days after treatment with each compound , for each concentration tested , are shown in fig6 . it is observed therein that the compound ( iiib ) in accordance with the invention exhibits a greater activity than that of the comparative compound gr24 , in particular at the lowest doses . a dose - response test for evaluating the activity of the compounds by deposition at node 3 was carried out according to the protocol described above with reference to experiment 2 , for the compound in accordance with the invention ( iia ) and for the comparative compounds gr24 , comp . 3 and comp . 4 . concentrations of 10 nm , 100 nm and 1 μm were tested . a sample consisting only of the solvent , and without active compound (“ ctl 0 ”), was also tested as a negative control . a nontreated (“ nt ”) control was also carried out . the results obtained ( mean data on 24 plants ) are shown in fig7 . it is observed therein that the compound in accordance with the invention ( iia ) exhibits an activity which is greater than the comparative compounds provided by the prior art , comp . 3 and comp . 4 , this being at all the doses tested . a dose - response test for evaluating the activity of the compounds by deposition at node 3 was carried out according to the protocol described above with reference to experiment 2 , for the compound in accordance with the invention ( iia ) and for the comparative compounds gr24 , comp . 5 and comp . 6 . concentrations of 10 nm and 100 nm were tested . a sample consisting only of the solvent , and without active compound (“ ctl 0 ”), was also tested as a negative control . a nontreated (“ nt ”) control was also carried out . the results obtained ( mean data on 24 plants ) are shown in fig8 . it is observed therein that the compound in accordance with the invention ( iia ) exhibits an activity which is greater than the comparative compounds provided by the prior art , comp . 5 and comp . 6 , this being at all the doses tested . the activity of the compound ( iia ) in accordance with the invention on bud growth at node 4 was evaluated at doses respectively of 0 . 1 nm , 1 nm , 10 nm and 100 nm , by treatment at node 4 . the gr24 compound was tested at the same concentrations , as comparative compound . for this , solutions containing each compound to be tested , in 1 % acetone , 4 % polyethylene glycol 1450 and 50 % ethanol , were used . 24 plants were sown per treatment . 8 days after sowing , the treatment was carried out on the axillary bud at node 4 , by application of 10 μl of each solution to be tested , directly on the bud , by means of a micropipette . the lateral outgrowths at nodes 1 and 2 were removed in order to encourage the growth of the axillary buds at the higher nodes . the sprouting of the axillary buds at node 4 was measured 8 days after the treatment by means of a digital sliding caliper . the results , expressed as length of bud / branch 8 days after treatment with each compound , for each concentration tested , are shown in fig9 . the control without treatment ( 0 nm ) is also represented in this figure . it is observed therein that the compound ( iia ) in accordance with the invention exhibits , after treatment at node 4 , an inhibitory activity on bud growth at node 4 which is equivalent to that of gr24 at the strongest concentrations , and slightly better at the lowest concentration of 0 . 1 nm . the activity of the compound ( iiia ) in accordance with the invention on bud growth at node 3 was evaluated at a dose of 1000 nm by treatment at node 3 . the gr24 compound was tested at the same concentration as comparative compound . for this , solutions containing each compound to be tested , in 1 % acetone , 4 % polyethylene glycol 1450 and 50 % ethanol , were used . 24 plants were sown per treatment . 8 days after sowing , the treatment was carried out on the axillary bud at node 3 , by application of 10 μl of each solution to be tested , directly on the bud , by means of a micropipette . the lateral outgrowths at nodes 1 and 2 were removed in order to encourage the growth of the axillary buds at the higher nodes . the sprouting of the axillary buds at node 3 was measured 8 days after the treatment by means of a digital sliding caliper . the results , expressed as length of bud / branch 8 days after treatment with each compound , for each concentration tested , are shown in fig1 . the control without treatment ( 0 nm ) is also represented in this figure . it is observed that the compound ( iiia ) in accordance with the invention exhibits , after treatment at node 3 , an inhibitory activity on bud growth at node 3 which , although less than that of gr24 , is highly significant . for this example , ramosus ( rms1 ) hyperbranched pea ( pisum sativum l .) mutants were used . more particularly , rms1 ( rms1 - 10 ) hyperbranched mutant plants were used . the nutritive solution ( 100 %) was prepared by adding the following macronutrients to 1000 l of water : hno 3 ( 0 . 28 l ), ( nh 4 ) 2 hpo 4 ( 120 g ), ca ( no 3 ) 2 ( 40 g ), mg ( no 3 ) 2 ( 140 g ), kno 3 ( 550 g ), ( nh 4 ) 2 moo 4 ( 0 . 05 g ), h 3 bo 3 ( 15 g ), mnso 4 . h 2 o ( 2 g ), znso 4 . 7h 2 o ( 1 g ), cuso 4 . 5h 2 o ( 0 . 25 g ), sequestrene ® ( 10 g ) ( fe - edta solution ). the pea seeds were germinated in moist sand for 6 days , then placed in holes of a lid ( 35 holes / lid , 20 mm in diameter ) of an opaque pvc pot containing the hydroponic culture solution ( 47 l , ph 5 . 8 ). in a first experiment , acetone or the compound to be tested ( dissolved in acetone ) was added to the hydroponic culture solution so as to obtain a final concentration of 0 or 1 μm of compound to be tested and 0 . 01 % of acetone . the hydroponic culture solution was continually aerated by means of an aquarium pump and replaced each week . 8 days after the start of the treatment , the lengths of bud / branch ( nodes 1 to 6 ) were measured with an electronic sliding caliper . this experiment was carried out for the compounds according to the invention ( iia ) and ( iiib ), and also the gr24 compound as comparative compound . a negative control (& lt ;& lt ; ctl 0 & gt ;& gt ;), corresponding to a treatment with the solvent alone , was also carried out . the results ( mean data on 20 plants ), in terms of , on the one hand , length of the branches at nodes 3 to 5 and , on the other hand , plant height , are shown respectively in fig1 and 12 . these results demonstrate the activity of the compounds in accordance with the invention ( iia ) and ( iiib ) on all the branches of nodes 3 to 5 . a significant effect on plant height is also demonstrated , comparable between the comparative compound gr24 and the compound in accordance with the invention ( iia ), and greater for the compound in accordance with the invention ( iiib ). the same experiment was carried out for the compound in accordance with the invention ( ii ″ g ) and the comparative compound gr24 . dimethyl sulfoxide ( dmso ) or the compound to be tested , dissolved in dmso , was added to the hydroponic culture solution so as to obtain a final concentration of 0 or 3 μm of compound to be tested and 0 . 01 % of dmso . the results ( mean data on 10 to 12 plants ), in terms , on the one hand , of length of the branches at nodes 3 to 4 and , on the other hand , of plant height , are shown respectively in fig1 and 14 . these results demonstrate , for the compound in accordance with the invention ( ii ″ g ), an activity on all the branches of nodes 3 to 4 , and also an effect on plant height , which are both greater than those of the comparative compound gr24 . in this example , the toxicity of the compounds in accordance with the invention ( iia ) and ( iiib ), and of the comparative compound gr24 , was evaluated by deposition at node 3 on hyperbranched rms4 mutant plants described in the publication by johnson et al . ( 1997 ) and which do not respond to the hormonal action of strigolactones ( m3t - 946 line derived from the térèse variety ). the protocol used is in accordance with that described in example 4 above . compound concentrations of 100 nm and 3 μm were tested . a negative control consisting of the solvent alone (& lt ;& lt ; ctl 0 & gt ;& gt ;) was also tested . the number of dead buds following the treatment with 3 μm of compound was also determined after 8 days of treatment ( on groups of 48 plants ). the results obtained are shown in fig1 , for the length of bud / branch at node 3 , and in fig1 , for the number of dead buds after treatment . these results demonstrate the absence of effects of the compounds in accordance with the invention ( iia ) and ( iiib ) compared with a negative control , and between the two treatment doses . in the same way , no significant difference is notable regarding the number of dead buds following the treatment . in particular , the treatment with the compound ( iiib ) did not cause the death of any bud . in this example , the germinative activity of the compounds in accordance with the invention ( iia ) and ( iiib ) and of the comparative compound gr24 was evaluated on the parasitic plants : orobanche cumana , orobanche minor , striga hermonthica , phelipanche ramosa ( pv t and pv c ). two populations of phelipanche ramosa were used in this study , pathovar ( pv ) c and t , described in the publication by benharrat et al . ( 2005 ). seeds of phelipanche ramosa pathovar c were collected at saint martin de fraigneau , france , on broomrapes parasitizing winter oilseed rape ( brassica napus l .) in 2005 and seeds of phelipanche ramosa pathovar t were collected in sarthe , france , on broomrapes developing on hemp ( cannabis sativa l .) in 2007 . seeds of orobanche cumana wallr . were collected from broomrapes parasitizing sunflower ( helianthus annuus l . ), at longeville - sur - mer , france , in 2009 ; seeds of clover broomrape ( orobanche minor sm .) from a parasite of red clover ( trifolium pratense l .) were obtained from professor k . yoneyama ( utsunomiya university , japan ). seeds of striga hermonthica ( del .) benth were collected at gadarif , eastern sudan , in 1999 . the seeds are stored dry in the dark at 25 ° c . the compounds to be studied were resuspended in acetone at 10 mmol · l − 1 , then diluted with water to 1 mmol · l − 1 ( water / acetone ; v / v ; 99 / 1 ). dilutions of 1 × 10 − 3 mol · l − 1 to 1 × 10 − 15 mol · l − 1 were then prepared in a water / acetone mixture ( v / v ; 99 / 1 ). seeds of parasitic plants were surface - sterilized according to the protocol described in the publication by vieira dos santos et al . ( 2003 ), then resuspended in sterile water ( 10 g · l − 1 ) and distributed on a 96 - well plate ( in a proportion of 50 μl , i . e . approximately 100 seeds per well ). after preconditioning ( 7 days , 21 ° c ., in the dark , plate hermetically sealed , except for the seeds of s . hermonthica , which were preconditioned at 30 ° c . ), the compounds to be studied were added and the volumes adjusted to 100 μl with water ( water / acetone ; v / v ; 999 / 1 ). in a plate , a range of concentrations from 10 − 13 mol · l − 1 to 10 − 6 mol · l − 1 was applied for gr24 and ( iia ) and from 10 − 12 to 10 − 5 mol · l − 1 for ( iiib ). controls were carried out with a water / acetone mixture ( v / v ; 999 / 1 ) and without seeds . the plates were incubated so as to allow germination ( 21 ° c ., in the dark or 30 ° c . for striga hermonthica .). after 4 days , the seeds which had germinated were counted under a stereomicroscope ( szx10 , olympus ). the seeds were considered to have germinated when the radicle was sticking out of the seed tegument . each germination test was repeated at least 3 times . for each compound tested , dose - response curves ( g = f ( c ), where g is the germination percentage and c the concentration ( mol · l − 1 )), and the ec 50 ( median effective concentration ) were modeled on the basis of a 4 - parameter logistic curve calculated with sigmaplot ® 10 . 0 . for each of the 3 compounds tested , the ec 50 concentration for each parasite thus obtained is shown in fig1 . it is observed therein that the compounds in accordance with the invention exhibit a very weak activity , much lower than that of gr24 , on the germination of the seeds of parasitic plants , this being the case on the 4 parasites studied . the percentages of maximum germination induced by the compounds tested for each parasitic plant were determined . these percentages are given in table 2 below . the compounds in accordance with the invention advantageously exhibit an activity on the germination of the parasitic plants which is much weaker than the comparative compound gr24 provided by the prior art . the set of results above demonstrates that the compounds according to the invention , and in particular the compounds corresponding to formulae ( iia ) and ( iiib ), have a biological activity for the control of branching which is comparable to that of natural strigolactones and to the synthetic analogs gr24 and gr5 of the prior art , while at the same time being much easier to prepare than these synthetic analogs and exhibiting less cytotoxicity . these compounds according to the invention also make it possible to dissociate the activity on branching and that on the germination of broomrape and of striga hermonthica . the description above clearly shows that , by virtue of its various characteristics and their advantages , the present invention achieves the objectives that it set itself . in particular , it provides compounds which are simple to synthesize and which exhibit a considerable biological activity of branching inhibition in higher plants , so that the treatment of such plants with these compounds makes it possible to control their growth and their architecture entirely optimally , what is more by means of low amounts of compound , with a view to improving crop yield . benharrat et al . 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