Synthesis of Topsentin‐A, A Bisindole Alkaloid of the Marine Sponge Topsentia genitrix

Abstract

ring sponge TOp8mtM g e n i t r k , has been achieved starting from 3-acetylindole. The synthesis of topsentin-A, a bisindole alkaloid isolated from the ma- Recently, we reported the isolation from the marine sponge T o p e e n t i a g e n i t r kof three related basic compounds, topsentin-AU), -el(?) and -B2(2) pertaining to a new type of bisindole alkaloids. The structure determinations were based on their spectral properties and, in particular, on homo-and heterocorrelated 2D NWR experiments"). These derivatives are presumed to derive from the biocondensation of two tryptophan units. total synthesis of topsentin-A starting from 3-acetylindole. This synthesis is based on the rearrangement, reported by Koga et al.(283), of 1,1-dimethyl-1-phenacylhydrazinium bromide (1) into 12-phenyl-lH-imidazol-4yllphenylmethanone (2). of a N to N migration of the phenacyl to give l,l-dimethyl-2-phenacylhydrazine 2 OH H 3 OH Br --

Synthesis and MRSA PK inhibitory activity of thiazole containing deoxytopsentin analogues

“…20 and 21. Our proposed synthesis of the desired α-oxo-1H-indole-3-thioacetamides 11-14 required the prior synthesis of carbonylnitrile precursors (27)(28)(29)(30). Although Jonosik et al 32 reported a method to synthesize variably functionalized indolyl-3-carbonylnitriles over three steps from indole (31), we opted for the one pot three step method originally developed by Hogan and Sainsbury, 33 and subsequently frequently utilized by Horne and co-workers.…”

“…We shed new light on known syntheses of -bromo-1-(1H-indol-3-yl)-ethanones (15)(16)(17)(18) and indolyl-3-carbonylnitriles (27)(28)(29)(30) and in the process have gained new mechanistic insight into these useful transformations. Finally, we have confirmed the pivotal contribution of the piperazine-2-one and imidazole rings to the MRSA PK inhibition of cis-3,4-dihydrohamacanthin B and bromodeoxytopsentin respectively.…”

“…in a 1:1 mixture of CHCl 3 and EtOAc to selectively brominate aryl methyl ketones. The King et al method was later adapted by Braekman et al 30 to deliver 2-bromo-1-(1H-indol-3-yl)-ethanone (15, 37% yield) and the undesired dibrominated product (19, 5% yield). Table 1) with a view to increasing the yield of the desired product and recoverable yield of the 3-acetylindole precursor, in addition to minimizing the yield of 19.…”

Marine Bi-, Bis-, and Trisindole Alkaloids

“…46 This analogous condensation strategy has been used on two further occasions by Tsujii et al 25 and Miyake et al 47 While this cyclic condensation approach is both an elegant and relatively uncomplicated method of synthesizing topsentin analogs, it lacks the regiospecificity necessary for an efficient synthesis of those analogs with differently substituted indole moieties.…”

“…Bartik recognized that all three compounds exist as a mixture of slowly interconverting imidazole tautomers in neutral solution, resulting in the doubling of resonances in the 1 H and 13 C NMR spectra of these compounds. 24 The isolation of this initial cohort of three topsentin metabolites was followed by the synthesis of isotopsentin (45) and hydroxytopsentin (46) and the isolation of 4,5-dihydro-6 00 -deoxybromotopsentin (47) (later renamed spongotine A) 26 collected in the Caribbean. 25 In the literature, the trivial name spongotine has been generally reserved for dihydrotopsentin analogs (mostly, but not exclusively, isolated from the genus Spongosorites) in which an acylimidazoline moiety replaces the acylimidazole moiety characteristic of topsentins.…”