Insights into the Biosynthesis of Cyclic Guanidine Alkaloids from Crambeidae Marine Sponges

Abstract

Among the outstanding chemical diversity found in marine sponges,c yclic guanidine alkaloids,p resent in species of the family Crambeidae,a re particularly attractive,n ot only because of their unique chemical features,b ut also due to ab road range of biological activities.D espite ag rowing interest in these natural products as therapeutic agents,t heir metabolic pathway has not been experimentally investigated. Ex situ feeding experiments using radiolabeled precursors performed on the Mediterranean sponge Crambe crambe suggest arginine and fatty acids as precursors in the metabolic pathway of crambescins.As ubsequent bio-inspired approach supported the change of paradigm in the metabolic pathway of cyclic guanidine alkaloids.Alarge part of the chemical diversity of this family would therefore originate from at ethered Biginelli-like reaction between C-2/C-3 activated fatty acids and ac entral guanidinylated pyrrolinium.

Recent Advances on Marine Alkaloids from Sponges

“…One hypothesis is as follows: Larginine was oxidized or decarboxylated, and then reacted with activated fatty acid precursors to produce bicyclic guanidine alkaloids. [104] The synthetic guanidinopyrrolinium was decarbonylated to produce compounds 39 and 55-57. The other hypothesis was verified by an isotope tracing method, and the guanidinopyrrolinium was esterified with guanidyl monohydric alcohol to produce compound 58 and its analogues.…”

“…The biosynthetic hypotheses of the alkaloids are shown in Scheme 3. One hypothesis is as follows: l ‐arginine was oxidized or decarboxylated, and then reacted with activated fatty acid precursors to produce bicyclic guanidine alkaloids [104] . The synthetic guanidinopyrrolinium was decarbonylated to produce compounds 39 and 55 – 57 .…”

“…The other group possessed a tetrahydrofuran including compounds 47 , 48 and 62 . The synthesis of these alkaloids were associated with the fusion of free guanidine and various α , β ‐unsaturated diketone initiated from the coenzyme A and coenzyme A derivatives [104] …”

Investigating the structure-activity relationship of marine polycyclic batzelladine alkaloids as promising inhibitors for SARS-CoV-2 main protease (Mpro)

“…Chemically, they feature two main fused guanidinic portions linking together via an ester functionality, where a principle tricyclic system named clathriadic acid is assembled to another clathriadic acid or a crambescin bicyclic moiety [ 30 ]. Biogenetically, those marine alkaloids are supposed to be generated via sequential modes of cyclization between a polyketide-derived chain and a putative guanidine precursor along with different oxidation degrees to afford such complex metabolites [ 29 , [31] , [32] , [33] ].…”

Investigating the Structure-Activity Relationship of Marine Polycyclic Batzelladine Alkaloids as Promising Inhibitors for SARS-CoV-2 Main Protease (Mpro)

“…Chemically, they feature two main fused guanidinic portions linking together via an ester functionality, where a principle tricyclic system named clathriadic acid is assembled to another clathriadic acid or a crambescin bicyclic moiety [26]. Biogenetically, those marine alkaloids are supposed to be generated via sequential modes of cyclization between a polyketide-derived chain and a putative guanidine precursor along with different oxidation degrees to afford such complex metabolites [25,[27][28][29].…”