Many attempts have been made to prepare aryl boronic acids and their esters which show a preferential affinity for tumor tissues for use in radiation therapy of neoplatic disorders (1,2). The data of Soloway, as extended and refined by Hansch and his coworkers, successfully correlates the low lipid solubility and electron releasing substituents of phyenl boronic acid derivatives with increased tumor concentration (3,4,5). However, most of these organoboron compounds do not produce a sufficiently high tumor-to-normal tissue boron concentration ratio for practical use in human cancer chemotherapy by the neutron capture technique. The knowledge that several chemical substances are preferentially taken up by tumor tissue provides the medicinal chemist the opportunity of rationally designing potential tumor inhibiting compounds linked to these carrier molecules (6,7). For the initial phase of attempts to successfully combine boronic acids or their esters with tumor concentrating material, it was deemed desirable to prepare a homologous series of aryl mono- and diboronic acids

Irradiation of a tryptamine linked through its side-chain nitrogen to an alkylidene malonate residue results in an intramolecular [2 + 2] cycloaddition to the indole 2,3-double bond. The resultant cyclobutane undergoes spontaneous retro-Mannich fission to produce a spiro[indoline-3,3-pyrrolenine] with relative configuration defined by the orientation of substituents in the transient cyclobutane. The novel tandem intramolecular photocycloaddition- retro-Mannich (TIPCARM) sequence leads to a spiropyrrolidine which is poised to undergo a second retro-Mannich fragmentation [TIPCA(RM)₂] that expels the malonate unit present in the photo substrate and generates transiently an indolenine. The indolenine undergoes rearrangement to a β-carboline which can undergo further rearrangement under oxidizing conditions to an oxindole. Three oxindole natural products, coerulescine, horsfiline and elacomine, were synthesized using this strategy. The TIPCARM strategy was extended to an approach that would encompass the Vinca alkaloids vindorosine and minovine. In this case, the TIPCARM sequence was followed by an intramolecular cyclization that provided tetracyclic ketone 5.86 containing rings A, B, C and D of vindorosine. A tetracyclic intermediate was synthesized which could also provided access to the Vinca alkaloid minovine. / Graduation date: 2012