The synthesis and medicinal applications of pyrogallol4arenes
Carey, Stephen (2006) The synthesis and medicinal applications of pyrogallol4arenes. PhD thesis, Dublin City University.
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To date almost all pyrogallolarenes reported in the literature have been prepared from alkyl aldehydes. We were interested in preparing more pyrogallolarenes from commercially available benzaldehydes. On synthesising these compounds we discovered that they are structurally unique, compared to previously reported pyrogallolarenes, as they exist in a rctt chair conformation as determined by X-ray crystallography and 1HNMR.
We also discovered from our synthetic studies that the yields for the pyrogallolarenes depend strongly on the electron donating/withdrawing ability of substituents placed in the benzaldehyde, the more electron withdrawing the higher the yield. We also discovered a unique metal salt effect on the condensation of pyrogallol with 4-fluorobenzaldehyde that doubled the yields o f the resulting macrocycle. Interestingly, this effect is absent with the condensation of pyrogallol with alkyl aldehydes. The role of steric effects, using bulky substituted benzaldehydes was also investigated to determine whether the stereochemical outcome for these condensation reactions could be controlled.
The further derivatisation of the pyrogallolarenes was also investigated. The preparation of partially and completely alkylated derivatives of these macrocycles was of interest to us. We found that the introduction of acetate groups could be readily accomplished, however other alkyl groups could not be efficiently introduced into the pyrogallolarenes. The partially and completely alkylated acetate derivatives of pyrogallolarene were screened for biological activity against HIV-1. It was discovered that the partially alkylated derivatives possessed higher selectivity indexes than the completely alkylated derivatives indicating that biological activity may not be dependent on charge.
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