Synthesis of 2,2'-Dihydroxybisphenols and Antiviral Activity of Some Bisphenol Derivatives.

Abstract

Triphenylmethane-type bisphenols have antioxidant activity, 1,2) and some of the derivatives show anticancer activity.3)Recently, we reported a conventional procedure for the preparation of triphenylmethane-type 2,2Ј-dihydroxybisphenols. 4) For the synthetic application of the procedure and biological evaluation of the related compounds, we attempted to synthesize diphenylmethane-type 2,2Ј-dihydroxybisphenol derivatives with some aliphatic aldehydes as starting material. In this paper, we wish to report the syntheses of some 2,2Ј-dihydroxybisphenols for lead compounds and also to communicate significant antiviral activities of some of the related compounds by the plaque reduction assay. 5) Results and DiscussionRegioselective syntheses of 2,2Ј-dihydroxybisphenols (5a-d) with aliphatic aldehydes (2-4) were achieved in good yields according to the procedure described previously.4) The results are summarized in ) and 4,4Ј-dihydroxybisphenol (10) 4) (see Fig. 1) were examined by plaque reduction assay as described by Schinazi et al.5) The results (EC 50 : 50% effective concentration) of six compounds by this assay are summarized in Table 5. Compound 5b having an isobutyl group instead of the substituted aromatic ring had high cytotoxicity. Antiviral activity of the 2,2Ј-bisphenol series (6-9) increased in the order, 6Ͻ7Ͻ8Ͻ9 (see EC 50 values in Table 5). Higher antiviral activity was observed in the 4,4Ј-bisphenol derivative (10) than the 2,2Ј-bisphenol series (6-9). This most active compound (10) was estimated to have a 50% cytotoxic concentration (CC 50 ) of 25-30 mg/ml by additional experiments. The selectivity index (CC 50 /EC 50 ) of 10 was ca. 15.During the past five years, more than a few thousand reports with bisphenol as a key word have appeared, however, to the best of our knowledge, no report has dealt with the an-298 Notes Chem.

Synthesis and Antiviral Activities of Some 4,4'- and 2,2'-Dihydroxytriphenylmethanes

“…15) described in our previous paper. 1,2) In structural comparison of 3a to 3d, the introduction of two methoxy groups into a phenyl ring resulted in a slight reduction of the anti-HSV-1 activity, as well as decreased cytotoxicity. We also observed that the modification of 2,2Ј-dihydroxytriphenylmethane derivatives 4b to 4c, in which a phenyl ring is substituted to a pyridine ring, increases its activity and decreases its cytotoxicity.…”

“…3) Antiviral Activity Assay The antiviral activities of the compounds were measured by the plaque reduction assay 8) described in previous paper. 1,2) Calculated EC 50 values for the tested compounds are summarized in Table 4. Cytotoxicity Assay The antiviral activities of the compounds were examined as described below.…”

“…1,2) Our finding of anti-HSV-1 activity in this new class of dihydroxytriphenylmethane derivatives led us to further molecular modification of the substituents in the phenyl rings of the dihydroxytriphenylmethane template. In our previous studies, we observed that the introduction of halogen atoms in the phenyl rings of triphenylmethanes generally enhances cytotoxicity resulting in low selectivity indexes.…”

Synthesis and Antiviral Activities of Some 4,4'-Dihydroxytriphenylmethanes

“…In addition, there are a great many combinations of starting phenols and aromatic aldehydes to provide a considerable number of target compounds. Considering the results described in this paper, together with the information in our previous report on 2,2Ј-dihydroxytriphenylmethanes, 2) further study is warranted.…”

“…Using TFA as the catalyst for the preparation of the target compounds is conventional and usually gives good to moderate results. 6) The physical data for compounds (1)(2)(3) are summarized in Table 2. NMR-spectroscopic analyses confirmed the symmetrical structure of the target compounds (1b, 2a-d) ( Table 1).…”