Aurilol

The bromotriterpene aurilol (19) also was isolated from the sea hare Dolabella auricularia. Aurilol exhibits cytotoxicity against HeLa S3 cells with an IC50 of 4.3 pg/ml [36]. 

The sea hare Dolabella auricularia has furnished aurilol (628), which is cytotoxic (728) and for which the structure has now been fully assigned by total synthesis (729). The Indian Ocean red alga Chondria armata, a member of the Laurencia family, contains armatols A-F (629-634) (730). 

Suenaga K, Shibata T, Takada N, Kigoshi H, Yamada K (1998) Aurilol, a Cytotoxic Bromotriterpene Isolated from the Sea Hare Dolabella auricularia. J Nat Prod 61 515... 

Morimoto Y, Nishikawa Y, Takaishi M (2005) Total Synthesis and Complete Assignment of the Stereostructure of a Cytotoxic Bromotriterpene Polyether (+)-Aurilol. J Am Chem Soc 127 5806... 

Scheme 131 Asymmetric Shi epoxidations in the total synthesis of (+)-aurilol (633)...

Selective epoxidation of polyene compound has also achieved with ent 2, the enantiomer of ketone 2. In Morimoto s total synthesis of polyether (+)-aurilol, Shi epoxidation was utilized twice, with ketone 2 and ent-2, respectively." Epoxidation of 79 with ketone 2 gave epoxide 80 with high diastereoselectivity. Epoxide 80 underwent acid catalyzed 5-exo-tet cyclization to produce tetrahydrofuran 81 with the desired stereochemistry. Subsequently, diene 82 was selectively epoxidized with ent-2 only at the trisubstituted olefin to give epoxide 83. Epoxides 80 and 83 played important roles in setting stereocenters in the final product. 

In the first total synthesis of cytotoxic bromotriterpene polyether (+ )-aurilol (85) (Scheme 3.28) [58], Morimoto and coworkers reported that epoxide81, resulting from... 

The seven-member bromocyclic ether core of the marine natural products, (-l-)-enshuol 21 and (-l-)-aurilol 23, were furnished by treating 20 with A/-bromosuccinimide (NBS Scheme 42.8). (-l-)-aurilol 23 which was isolated from the sea hare, Dolabella auricularia, has displayed significant cytotoxicity against HeLa S3 cells. " ... 

Experimental details synthesis of the key bromide intermediate of (+)-aurilol (23) (Scheme 42.8). To a solution of alkene 20 (12.5 mg, 22p,mol) and molecular sieves 4 A (25 mg) in 0.4 mL of (CF3)2CHOH was added a portion of NBS (9.8 mg, 55 pmol) at 0°C under a nitrogen atmosphere, and the solution was stirred at the same temperature for 10 minutes. A 5-M aqueous solution of potassium hydroxide (3 mL) was added to the solution, and the aqueous layer was extracted with dichloromethane (3x3 mL). The organic layer was dried over anhydrous MgS04 and concentrated in vacuo. The residue was purified by flash column chromatography (hexane/ethyl acetate = 95 5 to 90 10 to 50 50) on 1.4 g of silica gel to yield crude products. The crude products were subjected to flash column chromatography (hexane/ether = 90 10 to 85 15) on 4g... 

Morimoto Y, Nishikawa Y, Takishi M. Total synthesis and complete assignment of the stereostmcture of a cytotoxic bromotriterpene polyether (+)-aurilol. J. Am. Chem. Soc. 2005 127(16) 5806-5807. 

Suenaga, K Shibata, T, Takada, N., Kigoshi, H and Yamada, K. (1998) Aurilol, a cytotoxic bromotriterpene isolated from the sea hare Dolabella auricularia.]. Nat. Prod., 61, 515-518. 

All carbon skeletons shown in Figure 23.9 were formd in different species of Laurencia (Chapter 13). Aurilol and auriculol are both cytotoxic to human adenosarcoma HeLa 3 (cervix) cells, with IC50 values of 4.3 and 6.7 pgml, respectively. Aplysiols A and B (Figure 23.9) are rare squalenoids isolated from an opisthobranch mollusk. 

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