Haouamines

Belostotskii, A. M. Calculated chemical shifts as a fine tool of conformational analysis an unambiguous solution for haouamine alkaloids, J. Org. Chem. 2008, 73, 5723-5731. 

Reactions of phenols and acyl chlorides in the presence of TfOH occur with 0-acylation (Friedel-Crafts acylation), while with concentrated TfOH, C-acylation (Fries rearrangement) is observed. A tandem Prins/Friedel-Crafts reaction has been reported for the construction of the indeno-tetrahydropyridine core of the haouamine alkaloids (Scheme 92). ... 

In a spectacular final sequence during his synthesis of haouamine A, Baran employed an intramolecular Diels-Alder reaction with alkyne dienophile 133 to yield cycloadduct 134. This material then underwent a retro Diels-Alder reaction (producing carbon dioxide) followed by ester hydrolysis to afford haouamine A. This Diels-Alder/retro-Diels-Alder cascade is remarkable since the benzene ring formed in this sequenee is not planar. 

Synthesis of (-)-Haouamine A Haouamine A (193) was isolated in 2003 from a marine ascidian Aplidium haouarianum) and displayed potent and selective cytotoxic activity against the HT-29 human colon carcinoma cell Une. Aube et al. [29] have culminated a formal... 

Haouamines A (1) and B (2) are a new class of cytotoxic alkaloids isolated from the marine ascidian Aplidium haouarianum collected off the coast of southern Spain [8]. Haouamine A exhibits strong and selective anticancer activity in the human colon carcinoma cell line HT-29 (IC, 0.1 pg/mL). The novelty of their heptacyclic frameworks makes the haouamines attractive targets for total synthesis. In 2008, Ishibashi s group reported a concise route to synthesize the indenotetrahydropridine unit of Haouamine A (Scheme 7.4) [9]. The construction... 

The species Aplidium haouarianum harvested in Tarifa (southern Spain), led to the discovery of a new class of alkaloids with a 3-aza-[7J-paracyclophane, represented by haouamines A and B. These complex structures were confirmed by X-ray analysis and are cytotoxic to the hxunan colon cancer cell line HT-29, with IC50 values of 0.1 pg ml (haouamine A) and 5pgml (haouamine B) (Garrido et al., 2003). Aplidium orthium from New Zealand has recently yielded orthidines A-F, a series of styrylgua-nidine dimers that inhibit the production in vitro of the superoxide ion and may thus represent a new class of antiinflammatory drugs (Pearce et al, 2008). 

Jeong, J.H. and Weinreb, S.M. (2006) Formal total synthesis of the cytotoxic marine ascidian alkaloid haouamine A. Org. Lett., 8, 2309-2312. 

---