**1. Introduction**

The structures of marine natural products continue to provide not only targets for total synthesis but also new templates for biological evaluation. Ascidians of the genus *Aplidium* are a notable source of structurally complex natural products, including meroterpenoids, many of which exhibit potentially useful biological properties [1]. In addition to our own discoveries of rossinone B (potent cytotoxin) from an Antarctic *Aplidium* sp. [2] and scabellone B (antimalarial) from a New Zealand collection of *Aplidium scabellum* [3], Fattorusso's group reported the structures of thiaplidiaquinones A (**1**) and B (**2**), two thiazine-meroterpenoids, from Mediterranean specimens of *Aplidium conicum* (Figure 1) [4]. Both **1** and **2** exhibited cytotoxicity towards the human leukemia T cell line Jurkat with IC50 ~3 μM with propidium iodide staining and flow cytometry data indicating that the natural products increased the frequency of subdiploid (apoptotic) cells caused by a rapid overproduction of intracellular reactive oxygen species (ROS) which in-turn led to a collapse of the mitochondrial transmembrane potential.

**Figure 1.** Structures of natural products thiaplidiaquinone A (**1**) and thiaplidiaquinone B (**2**).

The interesting structures of thiaplidiaquinones A and B and their associated biological activities piqued the interest of ourselves and others, leading to reported biomimetic syntheses of **1** and **2** [5,6]. In addition to natural products **1** and **2**, our synthesis also led to the corresponding dioxothiazine isomers **3** and **4**. To investigate elements of the structural basis of ROS generation and Jurkat cell line cytotoxicity reported for the isolated natural products **1** and **2** [4], we have evaluated **1**–**6** in a similar set of assays and have also included more comprehensive evaluation for antitumor activity at the National Cancer Institute (USA) as well as for antimalarial and anti-farnesyltransferase activities.
