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

Abstract

Abstract 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′) 1 H, 13 C 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.