John P. Helgeson

Cytokinins: Structure/activity relationships☆

Abstract Sixty-nine compounds, mostly purine derivatives and closely related substances, were tested for promotion of growth and regulation of organ formation in the tobacco bioassay to determine relationships between chemical structure and cytokinin activity. Forty-three substances were synthesized in this study, and 13 of these were reported for the first time. N 6 -Alkyladenines (I) varied in activity over a wide concentration range depending on the length of the alkyl chain. Starting with adenine, detectable at ⩾200 μM, activity increased with the chain length to an optimum for 6-pentylaminopurine detectable at ca. 0–001 μM, and then decreased to reach a barely detectable level for 6-decylaminopurine. The result of the incorporation of polar groups in the side chain was not necessarily reduction in activity. One hydroxyl group, as in zeatin (Id), improved the activity of 6-(γ,γ-dimethylallylamino)purine (Ib) if it affected it at all; two hydroxyl groups, as in 6-(2,3-dihydroxy-3-methylbutylamino)purine strongly reduced activity. Comparisons of 6-isoamylaminopurine with 6-(γ,γ-dimethylallylamino)purine and of other closely related pairs of compounds showed that a double bond in the side chain greatly increased cytokinin activity. Adenine derivatives with cyclic substituents in the N 6 -position (benzyl-Ic), cyclohexyl-, etc.) showed the same general range of activity, potentiation by unsaturation, and variation in activity with substituent size, etc. as did the alkyl derivatives. Heteroatoms in or on the substituent groups decreased activity (in the case of N or Cl) or had little effect (S for O in furfuryl). Of the mono-substituted adenines only the N 6 -derivatives definitely possessed cytokinin activity. The 1-(III), 3-(II), or 9-substituted adenines probably are inactive but could be activated by conversion to the N 6 -isomers. Except for slight activity in tests of high concentrations, which could be ascribed to contaminants, 7-substituted adenines were completely inactive. Modification in the adenine moiety lowered the cytokinin activity, often by 95 per cent or more. Substitution of N for the 8-C atom in kinetin and in 6-benzylaminopurine or S for the 6-amino N atom in 6-(γ,γ-dimethylallylamino)purine did not eliminate but drastically reduced activity in the tobacco bioassay. Elimination of the 6-amino group without substituting another group completely removed activity; thus, the purine derivatives, 1-benzylpurine and 1-(γ,γ-dimethylallyl)purine, were inactive in tests where the 1-adenine derivatives could be activated to give a positive response. Addition of a second substituent on the 1-or 3-position of N 6 -substituted adenines drastically reduced or eliminated cytokinin activity. It is suggested that the 1-position and possibly also the 3-position must be free. A second substituent in the N 6 -, 7-, or 9-position of N 6 -substituted adenine derivatives lowered but did not eliminate activity. Also, the disubstituted 1-adenine derivatives, 1,9-dibenzyladenine and 1,7-dibenzyladenine were active, presumably after rearrangement to the corresponding N 6 -substituted isomers.