Solid Phase Peptide Synthesis of Lissocilium Patella's Patellamide A

Patellamide A, a compound biosynthesized by Lissocilium Patella, has been found to be antineoplastic against murine leukemia cells. This compound is a cyclic peptide, containing oxazoline and a thiazole heterocycles, that adopts side-chain dependent conformational preferences that may play a role in the molecule's ability to passively permeate cell membranes. Though several successful solution phase syntheses of this compound have shown successful outcomes, total synthesis via solid phase peptide synthesis (SPPS) has yet to be conducted. Our goal is to construct modular Patellamide A mimics by synthesizing thiazole moiety-containing amino acids in solution and oxazoline moieties on solid support.  Linear peptide synthesis was made possible by HOBT and HBTU coupling reagents and a Liquid Chromatography Mass Spectrometer (LCMS) was employed to analyze coupled products. Even though the thiazole moiety seems to be the primary concern in ensuring enantionmerically selective stereomer and the cyclization of oxazoline unit, we have yet a succinct theory to justify this conjecture and, more importantly, to fully conclude whether Solid phase peptide synthesis of patellamide is attainable.