A green synthetic process for the preparation of water-soluble drugs: Pegylation of menadiol and podophyllotoxin

Abstract

Pegylation of drugs is a frequently employed strategy used to improve the pharmacokinetics and pharmacodynamics of drugs. Despite this, the virtues of pegylation as a green synthetic approach to enhance the water solubility of drugs has not been discussed. Using two well-known active pharmaceutical ingredients, menadiol sodium diphosphate (1) and the semisynthetic natural product, etoposide phosphate (3), green metrics for the processes of pegylation versus phosphorylation are presented and discussed. Menadiol (2) was prepared by an ultrasound mediated reduction of menadione (9). In a study done by the National Cancer Institute, PEG podophyllotoxin 12 was screened for activity against 60 different human cancer cell lines and the desired anticancer properties of podophyllotoxin (5) were retained. As podophyllotoxin (5) is a natural product, the concept of "green drugs" is espoused.