Synthesis of vinylglycine and haloenol lactones
Patel, Sravan Kumar
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Vinylglycine (VG) is a naturally occurring, non-proteinogenic amino acid and exists in both L- and D- isomeric forms. The D-VG was first extracted in 1974 from carpophores of a fungus, Rhodophyllus nidrosorus and the L-antipode was observed as an intermediate in a variety of biosynthetic mechanisms. Owing to its intriguing biological properties and use as a chiral synthetic molecule, VG has attracted many chemists to asymmetrically synthesize and utilize it in building pharmaceutically active compounds. The traditional problems of isomerization and racemization during synthesis as reported in the preceding research, described in chapter I, made us undertake a study and report a high yielding method to enantiomerically pure VG by a mild toluene reflux of a 2-nitrophenyl homocysteine analog (illustrated in chapter II). The second project deals with the synthesis of bromoenol lactone (BEL) analogs or haloenol lactones (HELs) as candidate anticancer and antibacterial agents. BEL was shown to inhibit multiple types of tumor cells through iPLA2 cascade mechanism, PAP-1 inhibition and mitochondria mediated apoptosis. Therefore three different analogs of BEL were synthesized and sent to Dr. Cummings’ laboratory to test their anticancer activity. Also these compounds were assumed, in part, to exhibit their activity against bacterial cell growth through the above mentioned mechanisms (as similar pathways exist in prokaryotes). Also, a β-lactam antibiotic inactivating enzyme, serine β-lactamase was thought to be a major target for these molecules. Growth inhibition study of E. coli and S. aureus was conducted at three different concentrations of BEL analogs as described in chapter III and a ring activated amine containing compound showed partial inhibition of S. aureus. In the near future, experiments to test the β-lactamase activity through synergistic studies with BEL analogs in combination with β-lactam antibiotics shall be conducted.