Gunda Georg and co-workers at the University of Minnesota reported in the Journal of Medicinal Chemistry on the addition of a phosphonooxymethyl group onto triptolide to increase its water solubility by greater than 3,580 times. (slight mistake: Scheme 2 in the paper has the use of benzoyl peroxide shown as “Bn2O2” when it should be “Bz2O2” – Bn2O2 would be benzyl peroxide). Another interesting point from this paper is that this natural product has multiple modes of action where it can covalently attach to proteins (XPB, xeroderma pigmentosum B) or non-covalently (DCTPP1, dCTP pyrophosphatase). Other modified attempts to form soluble prodrugs of this natural product (e.g. carboxylic acid, amino acid esters) resulted in difficult removal of the prodrug group.