New Structural Insights into Saraines A, B, and C, Macrocyclic Alkaloids from the Mediterranean Sponge Reniera (Haliclona) sarai

Abstract

The structural peculiarity of saraines A, B and C, wherein a zwitterionic‐like form is present due to the coordination of a nitrogen atom to the C‐2 aldehyde by a strong proximity effect, has been further extended by experimental and theoretical evidences. They include the detection of [2M + H]+ clusters in electrospray ionization mass spectrometry in the positive ion mode of a water/acetonitrile solution, whereas only signals corresponding to [M + H]+ ions are detectable after addition of trifluoroacetic acid to the same solution. The zwitterionic form can be trapped to give O‐methyl derivatives only by reaction with a strong alkylating agent such as Meerwein's reagent. DFT calculations carried out on the core structural model suggest that the nucleophilic N‐1 atom in the minimized conformation is at a suitable distance from the carbonyl group and also defines an approach angle in good agreement with the Bürgi–Dunitz model. Antibacterial and hemolytic activities and inhibition of acetylcholinesterase (AChE) assays have been evaluated for saraines A–C in comparison to those of saraines 1–3 and isosaraine 1, all the metabolites isolated from the sponge Reniera (Haliclona) sarai collected in the Northern Adriatic sea.

Does the Chemical Diversity of the Order Haplosclerida (Phylum Porifera: Class Demospongia) Fit with Current Taxonomic Classification?

“…(l " Fig. 5) [73,74]. Both piperidine cycles are also connected through the C-4/C-5′ bond, but in the case of saraines A-C, other connections were established between both cycles.…”

Natural Products from the Marine Sponge Subgenus Reniera

“…Saraines A–C ( 28 – 30 ) ( Figure 3 ) were obtained from the Mediterranean sponge R. sarai and exhibited a broad spectrum of biological activities, including insecticidal and acaricidal potency to the arthropoda Macrosiphum euphorbiae (Thos. ), Tetranychus urticae Koch, and Aedes aegypti L.; strong inhibitory effect on Streptococcus agalactiae and AChE; and high hemolysis [ 26 , 27 , 28 ]. Chemical synthesis of compound 28 had first been achieved by Garg and coworkers in 2006 [ 29 ].…”

Organocatalytic Asymmetric Synthesis of an Advanced Intermediate of (+)‐Sarain A

“…(+)‐Sarain A ( 1 , Figure 1) is one of the polycyclic alkaloids [1] isolated from the Mediterranean sponge Reniera sarai collected in the bay of Naples (Italy) by Cimino et al [2] . This group of alkaloids displayed antitumor, antibacterial, insecticidal, [3a] and anticholinesterase [3b] activities. Sarain A possesses an unusual chemical structure featuring a 2,8‐diazatricyclo[5.4.0.0]‐undecane [4, 11] core pendent with a 13‐ and a 14‐membered macrocyclic rings, seven stereogenic centers, including a quaternary carbon atom, and an amine–aldehyde bonding interaction.…”