Ruth Y. Schmitz

Cytokinin antagonists: Synthesis and physiological effects of 7-Substituted 3-Methylpyrazolo[4,3-d]Pyrimidines

Abstract A series of sixteen pyrazolo[4,3- d ]pyrimidine derivatives has been synthesized and tested for cytokinin antagonist activity in the tobacco bioassay

Cytokinins: Synthesis and growth-promoting activity of 2-substituted compounds in the N6-isopentenyladenine and zeatin series

Abstract Fourteen compounds were tested for relative promotion of cell division and growth (cytokinin) activity in the tobacco bioassay. The results suggested that 2-substituted- N 6 -(hydroxy)isopentenylaminopurines were generally less active than their unsubstituted couterparts. Thus, a 2-OH substituent greatly lowered cytokinin activity in both the isopentenyl and hydroxyisopentenyl (zeatin) series, while 2-NH 2 and 2-SCH 3 groups had a lesser effect on activity and a 2-Cl substituent had a negligible effect. Mass spectra were determined for all of the 9-β- d -ribofuranosides and for a number of the purines as well; the fragmentation patterns were consistent and characteristic, providing a possible systematic approach to the identification of new 2-substituted- N 6 -(hydroxy)isopentenyladenines.

Comparison of cytokinin activities of naturally occurring ribonucleosides and corresponding bases

Abstract Cytokinin activities in the tobacco bioassay have been determined for four adenosine derivatives known to be components of wheat germ t RNA: 6-(4-hydroxy-3-methyl-2-butenylamino)-9-β- d -ribofuranosylpurine, 6-(3-methyl-2-butenylamino)-9-β- d -ribofuranosylpurine, 6-(4-hydroxy-3-methyl-2-butenylamino)- 2-methylthio-9-β- d -ribofuranosylpurine, and 6-(3-methyl-2-butenylamino)-2-methylthio-9-β- d -ribofuranosylpurine. Also determined and compared with the four natural components of t RNA were the activities of the four 3-methylbutylamino analogs of the naturally occurring species and the eight substituted purines corresponding to both sets of ribonucleosides. The systematic structural modifications within this group of sixteen compounds were reflected in the variations in cytokinin activity with the level of modification.

Synthesis of 2-methylthio-cis- and trans-ribosylzeatin and their isolation from Pisum tRNA

Abstract The cis isomer of 6-(4-hydroxy-3-methyl-2-butenylamino)-2-methylthiopurine and its 9-β- and 9-α- d -ribofuranosyl derivatives have been synthesized and their physical and spectroscopic properties are described. The biological activities of these compounds have been determined in the tobacco bioassay and are compared with those of 6-(4-hydroxy-3-methyl-trans-2-butenylamino)-2-methylthiopurine and its β-ribofuranoside. The 6-(4-hydroxy-3-methyl-2-butenylamino)-2-methylthio-9-β- d -ribofuranosylpurine (ms-ribosylzeatin) isolated from a Pisum tRNA preparation was shown to consist of both isomers, which were separated by TLC and identified by comparisons of UV and MS with those of the synthetic compounds.

Cytokinins with different connecting links between purine and isopentenyl or benzyl groups

Abstract Using the tobacco bioassay a comparison was made between the cytokinin activities of the following series of compounds with different connecting links (6-NH, S, O, CH2) between the purine ring and isopentenyl or benzyl groups: 6-(3-methyl-2-butenylamino)purine (1a), 6-(3-methyl-2- butenylthio)purine (1b), 6-(3-methyl-2-butenyloxy)purine (1c), and 6-(4-methyl-3-pentenyl)purine (1d); 6-benzylaminopurine (2a), 6-benzylthiopurine (2b), 6-benzyloxypurine (2c), and 6-(2-phenethyl)purine (2d); also 6-trans-styrylpurine (3), the synthetic precursor of 2d. All possess cytokinin activity, thus providing evidence that the intact base, consisting of nucleus and sidechain at the purine 6-position, is necessary and sufficient for such activity as measured in the tobacco bioassay. The biological activity in the 6-(3-methyl- 2-butenyl-X)purine series decreases as a function of the linkage group in the order X = NH > CH2 > S ⪢ O and in the 6-benzyl-X-purine series in the order X = NH > CH2 = O ⪢ S. The 6-trans-styrylpurine (3) is about equally active as 6-(2-phenethyl)purine (2d).

Cytokinins: Synthesis and biological activity of ureidopurines

Abstract Series of 6-aryl- and 6-alkylureidopurines have been prepared by the reaction of the appropriate isocyanate with adenine protected at the 9-position by the 1-ethoxyethyl group, followed by removal of this blocking group. The representative 6-ureidopurines were compared with 6-benzylamino-, 6-furfurylamino-, and 6-phenylaminopurine and with N , N ′-diphenylurea for cytokinin (growth-promoting) activity in the tobacco bioassay. Seven of the compounds [6-phenylureidopurine, 6- o -tolylureidopurine, 6- m -chlorophenylureidopurine, 6-isopropylureidopurine, 6-allylureidopurine, and N -ethyl- N ′-phenyl- N -purin-6-ylurea] ranged in activity in the order listed from ca. 10% to 0·5% that of 6-benzylaminopurine (activity starting in the range from 3 × 10 −2 to 1 μM). All were equal to or more active than N , N ′-diphenylurea and induced maximal yields of tissue. One, p -tolylureidopurine, was only weakly active, starting at 1 μM, and failed to give maximum yield at any concentration. 6-Phenylureido-9-β- d -ribofuranosylpurine was also synthesized. Its activity, starting at ca. 0·1 M was d -ribofuranosylpurine. The three most active 6-ureidopurines [6-phenylureidopurine, 6- o -tolylureidopurine, and 6- m -chlorophenylureidopurine] promoted bud formation in tobacco callus cultures, and their action may differ from that of the 6-alkylamino- or 6-arylaminopurine type.

Cytokinins: Synthesis and biological activity of zeatin esters and related compounds☆

Abstract The esters of the highly active cytokinin zeatin [6-(4-hydroxy-3-methyl- trans -2-butenylamino) purine] with formic, propionic, and indole-3-acetic acids and of its 2-chloro-substituted derivative [2-chloro-6-(4-hydroxy-3-methyl- trans -2-butenylamino)purine] with acetic and propionic acids have been synthesized, and their growth-promoting activities in the tobacco bioassay have been determined and compared with those of four known, related compounds: zeatin, 6-(4-acetoxy-3-methyl- trans -2-butenylamino)purine, methyl 2-methyl-4-(purin-6-ylamino)- trans -crotonate, and 2-chlorozeatin. The five new esters were fully as active as any cytokinins we have tested in the tobacco bioaassy. The three zeatin esters were consistently, although only slightly, more active than zeatin, and each of the 2-chlorozeatin esters showed activity about twice that of zeatin on a molar basis.

Cytokinins: Synthesis of 2-, 8-, and 2,8-substituted 6-(3-methyl-2-butenylamino)purines and their relative activities in promoting cell growth

Abstract We have synthesized 2- and 8-monosubstituted and 2,8-disubstituted derivatives of the cytokinin 6-(3-methyl-2-butenylamino)purine (N6-isopentenyladenine) and have shown the dependence of growth-promoting activity in the tobacco bioassay upon the position, number, and type of substituent. The representative substituent groups were MeS, Me, MeSO2, C6H5CH2S, HS and Cl. The 8-methyl derivative was exceptional in being more active than the unsubstituted parent compound. In general, substitution in the 8-position decreases activity less than substitution in the 2-position, with the exception of the electron-attracting methylsulfonyl. Substitution in both the 2- and 8-positions lowers the activity more than substitution at either single position on the adenine nucleus, with the exception of the 2,8-dimethyl derivative. The chloro and methylthio derivatives show activity in the same range as the methyl derivatives, and the mercapto compounds, which exist mainly as CS tautomers, show somewhat less activity than the corresponding methylthio compounds. Bulky (C6H5CH2S and MeSO2) and strongly electron-attracting (MeSO2) substituents cause relatively great reduction in cytokinin activity.

Cytokinins: Influence of side-chain planarity of N6-substituted adenines and adenosines on their activity in promoting cell growth

Abstract Eight compounds have been synthesized to define the relationship between side-chain planarity and cytokinin activity within a series of N 6 -substituted adenines and adenosines. These compounds and closely related ones have been tested for relative promotion of growth in the tobacco bioassay. It has been concluded from the examples available that side-chain planarity is important in imparting the highest order of cytokinin activity.

Fluorescent cytokinins: Stretched-out analogs of N6-benzyladenine and N6-(Δ2-isopentenyl) adenine

Abstract We have synthesized and compared the cytokinin activities in the tobacco bioassay of a series of benzologs of 6-(3-methyl-2-butenylamino)purine ( N 6 -(Δ 2 -isopentenyl)adenine) ( 1a ) and 6-benzylaminopurine ( N 6 -benzyl-adenine) ( 1c ). The linear benzo analogs 8-(3-methyl-2-butenylamino)imidazo[4,5- g ]quinazoline ( 2b ) and 8-benzyla-minoimidazo[4,5- g ]quinazoline ( 2c ) are active, while 9-(3-methyl-2-butenylamino)imidazo[4,5- f ]quinazoline ( 3b ) and 6-(3-methyl-2-butenylamino)imidazo[4,5- h ]quinazoline ( 4b ) are slightly active and 9-benzylaminoimidazo[4,5- f ]-quinazoline ( 3c ) and 6-benzylaminoimidazo[4,5- h ]quinazoline ( 4c ) are inactive. Compounds 2b and 2c represent the first examples of active cytokinins containing a tri-heterocyclic moiety. The above series of compounds demonstrates structural factors that affect cytokinin activity. These compounds also have interesting fluorescence properties which could render them useful as probes to study the mechanism of cytokinin action.