Isolation, Structure Determination, and Biological Activity of a Novel Alkaloid, Perophoramidine, from the Philippine Ascidian Perophora namei

Abstract

Chemical investigation of the Philippine ascidian Perophora namei has resulted in the isolation of a novel polycyclic alkaloid, perophoramidine (1). The structure of 1 was determined by the interpretation of 1D/2D NMR and MS data. Dehalogenation of perophoramidine (1) by ammonium formate catalyzed transfer hydrogenation confirmed the type and number of halogen atoms present in 1.

Molybdenum‐Catalyzed Asymmetric Allylic Alkylation of 3‐Alkyloxindoles: Reaction Development and Applications

“…36 Synthetic interests in these two and other related structures have been fueled by a desire to understand their structure-activity relationships as both compounds contain unusual structural features and exhibit significant biological activities. 37–38 Communesin B, in particular, shows both potent cytotoxicity against P-388 leukemia (ED 50 = 0.45 µg/mL) and insecticidal activity against silk worms (LD 50 5 µg/mL).…”

“…39 Perophoramidine is cycotoxic against the HCT-116 colon carcinoma cell line (IC 50 60 µM) and induces apoptosis via PARP cleavage. 40 …”

Biosynthesis of fungal indole alkaloids

“…88 A limited number of fungal alkaloids incorporating 4 have been reported, with communesins synthesized from Penicillium species and perophoramidine from Perophora namei being the most notable. 89, 90 Communesins, such as communesin F ( 9) , have been reported to disrupt microfilament and lead to cytotoxicity to mammalian cells. 89 The structural complexities of communesins, especially the cage-like polycyclic scaffold with four contiguous stereocenters and vicinal quaternary carbons, have attracted significant efforts from the total synthesis community.…”

A Diastereodivergent Synthetic Strategy for the Syntheses of Communesin F and Perophoramidine

“…4 Perophoramidine contains the equally unusual bis-amidine instead of bis-aminal functionality, possesses the alternate diastereomeric relationship between the vicinal quaternary centers, and lacks the azepine ring compared to communesins. Perophoramidine ( 2 ) exhibits cytotoxicity toward the HCT 116 human colon carcinoma cell line (IC 50 = 60 μM) and induces apoptosis via PARP cleavage.…”