The total synthesis of nummularine-F. New synthetic methods for ninhydrin derivatives

The first chapter of this dissertation begins with a short review of the cyclopeptide alkaloid literature from 1884 to the present, and ends by describing the first total synthesis of a 14-membered cyclopeptide alkaloid, nummularine-F. The synthesis employs a highly stereocontrolled strategy to introduce the correct absolute stereochemistry of the $\alpha$- and $\beta$-carbons of the $\beta$-hydroxyproline moiety, utilizing D-serine as its source of chirality. A successful cyclization of an activated ester forming the 14-membered macrocycle was achieved in good yield. The benzylic oxygen functionality was converted to a selenoxide which under went elimination to provide the desired double bond of the enamide unit. Removal of the tert-butyloxycarbonyl protecting group from the proline nitrogen followed by coupling the resulting secondary amine with dimethylglycine afforded nummularine-F. The second chapter of this thesis begins with a review of the ninhydrin literature, from 1910 to the present and ends by describing new synthetic methods for the preparation of a number of ninhydrin derivatives, which are important reagents for the detection of latent fingerprints on porous surfaces. A new synthesis of benzo (f) ninhydrin is first described, utilizing a high yielding and novel three step strategy which employs two novel oxidation reactions starting from commercially available materials. This methodology is then used for the preparation of two novel ninhydrin derivatives, 6-methoxybenzo (f) ninhydrin and thieno (f) ninhydrin. Two synthetic methods for the preparation of 5-methoxyninhydrin are also reported, with the second method employing a high yielding and novel, two step protocol starting with commercially available 6-methoxy-1-indanone. This methodology was then used for the preparation of ninhydrin and the novel ninhydrin derivative, 5-(methylthio)ninhydrin