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

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'-deimino-2',4'-bis(demethyl)-3'-oxoaplysinopsin (5) are isolated as 2 :3 and 1 :1 (E/Z) mixtures, respectively, from another dendrophylliid, Leplopsammia pruuofi, 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 (ll), or 1,3-dimethylhydantoin (10) give the prevalent natural aplysinopsins with high stereospecificity. The minor stereoisomers (2)-4, (2)-6, (E)-7, and (E)-5 are obtained by (E/2) photoisomerization under UV light of the condensation mixtures. The configuration is assigned from larger H-C(S)/C(Y) ' H , ' k 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 (2)-4 and (2)-6, or to C(5')=0/H-C(2) repulsion with (E)-7 or (E)-5. As the aplysinopsins undergo (E/Z) photoisomerizdtion also under the daylight conditions of the kIbOrdtOry, their isomeric composition in nature can not be presently assessed.

Chemical composition and release in situ due to injury of the invasive coral tubastraea (Cnidaria, Scleractinia)

“…The phylum Cnidaria possesses an array of secondary metabolites, mainly terpenes, and the soft coral group possesses more than 80 percent of all cnidarian compounds (HARPER et al, 2001;BLUNT et al, 2007BLUNT et al, , 2008. Despite the absence of accessible fleshy and soft tissues, scleractinian corals also produce secondary metabolites for defense and many of them are toxic to cells (FUSETANI et al, 1986;GUELLA et al, 1988;FUNG et al, 1997, KONTIZA et al, 2006predators (BAIRD et al, 2001) and competitors (DE RUYTER VAN STEVENICK et al 1988;KOH;SWEATMAN, 2000).…”

“…The use of the submersible sampling apparatus described by Schulte and collaborators (1991) is a method available to collect, in situ, trace quantities of organic compounds from seawater. This method provides a simple means of sampling the water around aquatic organisms for bioactive substances thus avoiding the use of large quantities of solvents for extraction (COLL et al, 1982;SCHULTE et al, 1991 (FUSETANI et al, 1986;GUELLA et al, 1988;RASHID et al 1995;IWAGAWA et al, 2008;MEYER et al, 2009). They also may function against competitors (KOH, 1997).…”

Potassium Thiocyanate‐Promoted One‐Pot Synthesis of (1,3‐Diaryl‐2,5‐dioxoimidazolidin‐4‐ylidene)acetates from Aryl Isocyanates and Alkyl Propiolates. Short Communication

“…C(5)-Unsaturated hydantoins are important as biological and pharmaceutical intermediates and as precursors to C(5)-substituted hydantoins and their subsequent a-amino acids [4 -6]. Classic methods for preparing these compounds are i) base-or acid-catalyzed condensations of 5-unsubstituted hydantoins with aldehydes, and unhindered or activated ketones [4] [5] and ii) reactions of aldehydes, certain ketones, and a-dicarbonyl compounds with diethyl hydantoinyl-5-phosphonate in the presence of a base [6]. Recently, threecomponent synthesis of 1-alkyl-3-(arylsulfonyl)-5-methylidenehydantoins has been reported [7] [8].…”

Discovery of Novel, Potent and Selective Glycine Receptor Modulators from Southern Australian Sponges

“…From several marine taxa such as sponge [140][141][142][143] , scleractinian coral [144][145][146][147] , anemone 148 and mollusc 149 , dozen monomeric aplysinopsins have been reported featuring a diverse pattern of bromination and methylation as well as different levels of oxidation and geometry (E vs. Z) 146,149 . Monomeric aplysinopsins are known to exert a range of biological activities particularly as anticancer and antidepressant agents [150][151][152] , inspiring numerous total syntheses [153][154][155][156] .…”

“…. Aplysinopsins methylated at N-2( exist predominantly as E isomer 144,145 . The isomer configuration and methylation pattern were also reported to play an important role in bioactivity, particularly in serotonin receptor modulation (described more detail in bioactivity section, page 129) 149,150 .…”