Studies Directed Towards Total Synthesis of Securine A and Securamine A

The aim of this research project was to synthesize securamine A (6) and to make use of the facile equilibrium between securamine A (6) and securine A (13) in the strategic design. The original synthetic strategy was to prepare these alkaloids based on the construction of the neopentyl alcohol 86 by coupling lithiated indole 58 with simple epoxide 85. However, we were not able to obtain any of the desired product in this model study. An alternative strategy was then employed for a total synthesis of these alkaloids based on the coupling of the indole ester 146 with the aldehyde functionality of advanced imidazole intermediate 120, which proceeded in good yield to give ester alcohol 147. A benzyl group was found to be the most compatible nitrogen protecting group for the indole 110 in the synthetic sequence. A key intermediate, protected oxime 169, was then formed by condensation of aldehyde 153 and BOM-protected hydroxylamine 168. Many attempts to chlorinate various neopentyl alcohols were tried; however, it seems that it will be necessary to remove the protecting group on the indole nitrogen in order for this step to be successful.