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International audience; Biosynthetic considerations inspired us to harness the templating properties offered by DNA to promote a [2+2] photoinduced cycloaddition. The method was developed based on the dimerization of (E)-aplysinopsin, which was previously shown to be unproductive in solution. In sharp contrast, exposure of this tryptophan-derived olefin to light in the presence of salmon testes DNA (st-DNA) reproducibly afforded the corresponding homo-dimerized spiro-fused cyclobutane in excellent yields. DNA provides unique templating interactions enabling a singular mimic of the solid-state aggregation necessary for the [2+2] photocycloaddition to occur. This method was ultimately used to promote the prerequisite dimerizations leading to both dictazole B and tubastrindole B, thus constituting the first example of a DNA-mediated transformation to be applied to the total synthesis of a natural product.

A new two-step approach toward the synthesis of aplysinopsin analogues 5-(1-R-1H-indol-3-ylmethylene)-2-aryl-3,5-dihydroimidazol-4-ones consisting in obtaining and reaction of 4-(1-R-1H-indol-3-ylmethilene)-2-Ar-4H-oxazol-5-ones with amines was developed. The configuration of starting compounds and final products was determined by 13С and 1H-nmr spectroscopy.

Guided by biosynthetic considerations, the total synthesis of dictazole B is reported for the first time. Experimental evidence for an easy access to challenging cyclobutane alkaloids of marine origin, which are often postulated to be biosynthetic precursors of more complex structures, is provided.

A new two-step approach toward the synthesis of aplysinopsin analogues 5-(1-R-1H-indol-3-ylmethylene)-2-aryl-3,5-dihydroimidazol-4-ones consisting in obtaining and reaction of 4-(1-R-1H-indol-3-ylmethilene)-2-Ar-4H-oxazol-5-ones with amines was developed. The configuration of starting compounds and final products was determined by 13С and 1H-nmr spectroscopy.

(.+-.)-Tubastrindole B (Ia) and a precursor of (.+-.)-tubastrindole E (Ib) are prepared by a ring-expansion cascade of a dictazole-type precursor.

Simple and stereoselective syntheses of aplysinopsins and their analogs from either methyl 2-[(2,2-disubstituted ethenyl)amino]-3-(dimethylamino)prop-2-enoates 11 or 5-[(dimethylamino)methylidene]imidazolidine-2,4-diones 20 are described. The structures of products are established by 1H- and 13C-NMR, and NOESY spectroscopy, and X-ray crystal-structure analysis.

Aza Wittig-type reactions of iminophosphoranes 21, derived from ethyl α-azido-β-(3-indolyl)propenoates and triphenylphosphine, with methyl isocyanate, carbon dioxide or carbon disulfide provide the corresponding heterocumulenes 22, 25 and 28 which undergo cyclization by the action of nitrogenous reagents completing the assemblage of the framework of aplysinopsin. Further deprotection leads to naturally occurring aplysinopsin analogues.

Some new aplysinopsin analogues were prepared by a simple coupling of N , N -(dimethylamino)methylidene substituted hydantoin, thiohydantoin, and thiazolone derivatives, with indole derivatives. Configuration around the exocyclic CC double bond was determined on the basis of long-range heteronuclear coupling constants using 2D HMBC correlation technique.

Five novel bis(indole) alkaloids, which were composed of two molecules of aplysinopsin have been isolated from a stony coral, Tubastraea aurea. Their structures were elucidated on the basis of spectroscopic methods.

Various aplysinopsin and β -carboline thiohydantoin analogues were prepared starting from ethyl 3-formyl-1H-indole-2-carboxylate by condensation with the active methylene group of 2-thiohydantoin, rhodanine, or thiobarbituric acid derivatives

The dendrophylliid Dendrophyllia sp. of Palawan contains the indole alkaloids 2′-demethylaplysinopsin (4) and 2′-demethyl-3′-N-methylaplysinopsin (6) and their 6-bromo analogues in H (Z/E) ratio larger than 95:5; these mixtures undergo facile photoisomerization to give mixtures richer in the (E) stereoisomer which undergo thermal isomerization to give back the original mixtures.