Pericosine

The chlorocyclohexene derivative from the marine microorganism Periconia byssoides, pericosine A (170), is 33 times more cytotoxic in the P-388 lymphocytic leukemia test (IC50 0.12 pg/ml) than the corresponding methoxy compound [131]. 

Usami Y, Ueda Y (2005) Synthetic Study Toward Antitumour Natural Product Pericosine A. Chem Lett 34 1062... 

Usami Y, Horibe Y, Takaoka I, Ichikawa H, Arimoto M (2006) First Total Synthesis of (-)-Pericosine A from (-)-Shikimic Acid Structure Revision and Determination of the Absolute Configuration of Antitumour Natural Product Pericosine A. Synlett 1598... 

Donohoe TJ, Blades K, Helliwell M, Waring MJ, Newcombe NJ (1998) The Synthesis of (+)-Pericosine B. Tetrahedron Lett 39 8755... 

Pericosine B, a secondary metabolite produced by a strain of Periconia bissoides [48], proved to be an interesting target compound due to its significant antitumoral activity. From a structural point of view, pericosine B (201, Scheme 33) can be considered as an unsaturated carbauronic acid or an hydroxylated shikimic acid derivative. 

In a work aimed at confirming the stereochemical assignment of pericosine B, Donohoe and co-workers [49] delineated a short route, based on direct dihydroxylation of the enantiomerically pure brominated... 

Pericosines A (216) and B have been isolated from a strain of Periconia byssoides, originally separated from the sea hare Aplysia... 

Pericosines A (145) and B (146) were cytotoxic on the P388 murine leukemia cell line, showing ICsoof 0.12 and 4.0 ig/ml respectively [179]. 

SCHEME 42.9. Enantioselective bromohydrin synthesis leading to (+)-pericosine A 26. 

An example of the intermolecular halo-O-functionaliza-tion, which involves the opening of the halonium intermediate with a water molecule, appears in Usami et a/. s synthesis of (+)-pericosine A 26." In Usami et al. s report, the enantioselective formation of bromohydrin intermediate 25 was derived from the enantioenriched cyclohexadiene 24 (Scheme 42.9). (+)-pericosine A 26 has been demonstrated to be an inhibitor of protein kinase epidermal growth factor receptor (EGFR) and human topoisomerase II as well as an antitumor agent against P388 in vivo ... 

Other than the LiBr/PPTS reagent, thionyl chloride (in the synthesis of (-l-)-danicalipm 14 A by Umezawa et al. ) and hydrochloric acid (in the syntheses of (-l-)-pericosine A 26" and blatteUastanosides A 55 and B 56 ) have also been used to promote the epoxide ring opening and to form the chlorohydrin stereoselec-tively (Scheme 42.16). 

Experimental details synthesis of the key chiral chloride intermediate 51 in the synthesis of (-l-)-pericosine A (26) (Scheme 42.16). To a solution of epoxide 50 (12.8 mg, 0.048 mmol) in Et20 (5mL) was added 1-M HCl (0.1 mL, excess) in Et20 at 0°C. After stirring for 1 hour, the solvent was removed in vacuo to give a crude residue that was purified by flash chromatography (silica gel, hexane/EtOAc, 2/1) to afford 51 (12.4 mg, 85%) as colorless crystals. 

Usami Y, Ohsugi M, Mizuki K, Ichikawa H, Arimoto M. Facile and efficient synthesis of naturally occurring carbasugars (-l-)-pericosines A and C. Org. Lett. 2009 11(12) 2699-2701. 

Yamada T, Iritani M, Ohishi H, Tanaka K, Minoura K, Doi M, Numata A. Pericosines, antitumour metabolites from the sea hare-derived fungus Periconia byssoides. Structures and biological activities. Org. Biomol. Chem. 2007 5(24) 3979-3986. 

Here again, there has been little work on the metabolites of fungi associated with mollusks. Isolated from the sea hare, Aplysia kurodai, the fungus Periconia byssoides produces in culture two cytotoxic derivatives, pericosines A and H, and four trilactones, macrosphelides E-H, which are devoid of activity (Numata et al, 1997b). The cytotoxicity of pericosines A and B on P-388 is notable with... 

Usami, Y, Suzuki, K., Mizuki, K., Ichikawa, H., and Arimoto, M. (2009a) Synthesis of (—)-pericosine B, the antipode of the cytotoxic marine natural product. Org. Biomol. Chem., 7, 315-318. 

Vinyllithium derivatives 128-131 have been generated through a bromine-lithium exchange with t-BuLi. In the case of 128, used in the synthesis of (-)-wode-shiol, a deprotonation of the alcohol functionality was performed prior lithiation [107]. Intermediates 129 were also used in the synthesis of triquinanes [102,108], meanwhile 130 acted as an intermediate in a synthetic route to (-i)-pericosine B [109]. Dianionic species 131 showed an unexpected intramolecular carbometalla-tion upon addition of TMEDA to give dilithiated dihydropyrroles, which finally reacted with different electrophiles [110]. 

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