Total Synthesis Of Grassystatin A And Synthesis Of Analogues Of Tasiamide B

This dissertation describes total synthesis of Grassystatin A and the synthesis of analogues of tasiamide B.Cathepsin E (CE) is an intracellular aspartic protease that is mainly present in the immune system and highly homologous to the aspartic protease cathepsin D (CD). In2009, Grassystatin A was isolated from a cyanobacterium, identified as Lyngbya cf. confervoides by Luesch and co-workers. During the biological evaluation, Grassystatin A was selective for CE over CD (30fold).We envisioned that the molecular can be assembled via amidation between the Asn and Leu residues because of the versatility in the construction of the precursors(2,3), low hinderance and absence of racemization during fragment coupling. The two fragments are prepared successfully through stepwise coupling strategy, starting from commercially available amine acids, and in presence of condensing agents HATU and HOAt. In the end, we completed the synthesis in4.5%yield.Tasiamide B, a linear octapeptide, was also isolated from the lipophilic extract of marine cyanobacteria Symploca sp. NIH304in2003by Moore et al. Eight analogues of Tasiamide B are designed and synthesized in the second part. The synthesis was carried out by stepwise coupling strategy from amino acid building blocks. The compounds are designed by changing N-terminal residue and C-terminal residue.