Unravelling Photochemical Relationships Among Natural Products from <i>Aplysia dactylomela</i>

Abstract

Aplydactone (<b>1</b>) is a brominated ladderane sesquiterpenoid that was isolated from the sea hare <i>Aplysia dactylomela</i> together with the chamigranes dactylone (<b>2</b>) and 10-<i>epi</i>-dactylone (<b>3</b>). Given the habitat of <i>A. dactylomela</i>, it seems likely that <b>1</b> is formed from <b>2</b> through a photochemical [2 + 2] cycloaddition. Here, we disclose a concise synthesis of <b>1</b>, <b>2</b>, and <b>3</b> that was guided by excited state theory and relied on several highly stereoselective transformations. Our experiments and calculations confirm the photochemical origin of <b>1</b> and explain why it is formed as the sole isomer. Irradiation of <b>3</b> with long wavelength UV light resulted in a [2 + 2] cycloaddition that proceeded with opposite regioselectivity. On the basis of this finding, it seems likely that the resulting regioisomer, termed “8-<i>epi</i>-isoaplydactone”, could also be found in <i>A. dactylomela</i>