Syntheses & Applications of Steroid-Amino Acid Conjugates & Complexes

Sesquiterpenoid- and steroid-amino acid conjugates demonstrate a broad array of interesting biological properties, as the different segments of the conjugate function collectively to regulate conformation, recognition, transport and solubility. The current project involved developing a facile methodology to synthesize metabolically stable facially amphiphilic conjugates by appending either amino acids (chapter 2) or cationic metal ligand-amino acid complexes (chapter 3) as hydrophilic segments on steroid progesterone and sesquiterpene amorpha-4,11-diene scaffolds. Aminosteroids and C-11 substituted steroids have attracted long lasting interest due to their diverse pharmacological properties. As the stereoselective C- 11beta functionalization of a steroid imposes severe steric hindrance due to the C-18 and C-19 angular methyl groups, access to 11beta-aminoprogesterone is a challenge. Chapter 2 describes stereoselective syntheses of a new family of aminosteroids: 11beta-aminoprogesterone (11 -NH2-Pro) (76) and its derivatives, including its glycine 77 and L-/D- alanine- 78/79 based conjugates, by nucleophilic substitution or reductive amination.