There is a competition between phenol and primary alcohol to form ester with the linker. The alcohol has higher nucleophilicity in this reaction condition, however its nucleophilicity hampers by higher steric hindrance. Since the phenol is not the phenolate form, it is less reactive than alcohols for nucleophilic reactions, in contrast the lower steric hindrance around the phenol increases its nucleophilicity. Therefore, a mixture of esters is expected. We were not able to separate the mixture by chromatography technique.

has been cited by the following article:

• TITLE: Synthesis and Antiproliferative Activities of Triphenylmethanol Conjugates of Leuprorelin

  AUTHORS: Ryan Beni, William Boadi, Kaleh Karim, Jawzah Alnakhli, Samiyah Alhamed

  KEYWORDS: Prodrugs, Leuprorelin, Polyphenols, Prostate Cancer, Triphenylmethanol, Prodrugs

  JOURNAL NAME: Open Journal of Medicinal Chemistry, Vol.9 No.2, June 10, 2019

  ABSTRACT: Leuprorelin® (LEP) is an FDA drug for breast cancer and prostate cancer treatment. There are several reported adverse effects such as transient hypertension, excessive salivation, and increased dysuria during treatment with LEP. In this study, the efficacy and toxicity of LEP were modified by using a drug delivery system to adjust the physicochemical properties. In this regard, Leuprorelin® conjugates of triphenylmethanol derivatives (TPMs) were synthesized as prodrugs. Comparative antiproliferative assays showed that LEP-TPMs conjugates had significantly higher antiproliferative activities than the corresponding non-covalent physical mixtures of the TPMs and LEP against human invasive ductal carcinoma (BT-549), human prostate carcinoma (PC3), human lung cancer (A549) and mouse pre-adipocytes (3T3-L1) cells.