EFFORTS TOWARDS THE ASYMMETRIC SYNTHESIS OF A HUMAN T-CELL LEUKEMIA VIRUS-1 PROTEASE INHIBITOR: A CHEMOSELECTIVE ZINC (II) ACETATE-TRIETHOXY SILANE REDUCTIVE PATHWAY TO THE INHIBITOR
The Human T-cell leukemia virus (HTLV-1) can cause leukemia and lymphoma in human beings and is transferred through various pathways that range from sharing syringes, blood transfusions, and from mother to child during birth.1 This particular disease effects Japan, Melanesia, South America, the Caribbean, and sub-Saharan Africa and was likely spread through the hunting of primates that were infected with the Simian T-lymphotropic virus type 1.2 In 2003, Akaji and coworkers disclosed a method for the preparation of a protease inhibitor that would be effective against HTLV-1.3 We became interested in determining if the process could be made more efficient by the asymmetric glycolate aldol addition reaction, which would already have certain functionalities present. To this end, we have developed a synthetic pathway towards the preparation of this compound. The pathway involves the application an oxazolidine-2-thione templated asymmetric glycolate aldol addition reaction, and aminolysis of the resultant glycolate side chain. The amide products generated via this process are under evaluation for their usefulness in chemoselective zinc (II) acetate-triethoxysilane based reduction to the corresponding amine substrates. Ultimately, these amine substrates transformed into the key component of the Akaji protease inhibitor by means of a unprecedented convergent process. 1. National Cancer Institute. http://www.cancer.gov/ [Accessed Mar 23, 2016]. 2. Calvignac-Spencer, S.; Adjogoua, E. Origin of Human T-Lymphotropic Virus Type 1 in Rural Côte d'Ivoire. EID. 2012, 5. 3. Akaji, K.; Teruya, K.; Aimoto, S. J. Org. Chem. 2003, 68, 4755-476.
Garrelts, Elizabeth, "EFFORTS TOWARDS THE ASYMMETRIC SYNTHESIS OF A HUMAN T-CELL LEUKEMIA VIRUS-1 PROTEASE INHIBITOR: A CHEMOSELECTIVE ZINC (II) ACETATE-TRIETHOXY SILANE REDUCTIVE PATHWAY TO THE INHIBITOR" (2019). University Research Symposium. 265.