Novel Aplysinopsin-Type Alkaloids from Scleractinian Corals of the Family Dendrophylliidae of the Mediterranean and the Philippines. Configurational-assignment criteria,stereospecific synthesis,and photoisomerization

From the scleractinian coral Tubastraea sp. (Dendrophylliidae) collected at Palawan, Philippines, 3′-deimino-3′-oxoaplysinopsin ( 4 ) and 6-bromo-3′-deimino-3′-oxoaplysinopsin ( 6 ) are now isolated as 5:2 mixtures of (E/Z) stereoisomers. The 3′-deimino-2′,4′-bis(demethyl)-3′-oxoaplysinopsin ( 7 ) and 6-bromo-3′-demino-2′,4-bis(demethyl)-3′-oxoaplysinopsin ( 5 ) are isolated as 2:3 and 1:1 (E/Z) mixtures, respectively, from another dendrophylliid, Leptopsammia pruvoti, collected near Marseille, Mediterranean coast of France. Larger amounts of these and related compounds, needed for a full structural determination, are obtained by synthesis. Thus, condensations of indol-3-carboxaldehyde (9) or of its 6-bromo derivative 14 with hydantoin (15) , 3-methylhydantoin (11) , or 1,3dimethylhydantoin (10) give the prevalent natural aplysinopsins with high stereospecificity. The minor stereoisomers (Z)- 4 , (Z)- 6 , (E)- 7 , and (E)- 5 are obtained by (E/Z) photoisomerization under UV light of the condensation mixtures. The configuration is assigned from larger H? C(8)/C(5′) ¹H, ¹³C couplings in the (E) than in the (Z) isomer, and, in the case of 4 and 6 , from NOE enhancement at Me? N(2′) on irradiation at H? C(8). The stereospecificity of the condensations is attributed to steric inhibition to planarity in the rate-limiting transition states, due to N(2′)/H? C(2) repulsion with (Z)- 4 and (Z)- 6 , or to C(5′)?O/H? C(2) repulsion with (E)–7 or (E)- 5 . As the aplysinopsins undergo (E/Z ) phostoisomerization also under the daylight conditions of the laboratory, their isomeric composition in nature can not be presently assessed.