Kabirimine, a New Cyclic Imine from an Okinawan Dinoflagellate

Abstract

On our quest for new bioactive molecules from marine sources, two cyclic imines (1, 2) were isolated from a dinoflagellate extract, inhibiting the growth of the respiratory syncytial virus (RSV). Compound 1 was identified as a known molecule portimine, while 2 was elucidated to be a new cyclic imine, named kabirimine. The absolute stereochemistry of 1 was determined by crystallographic work and chiral derivatization, whereas the structure of 2 was elucidated by means of spectroscopic analysis and computational study on all the possible isomers. Compound 1 showed potent cytotoxicity (CC50 < 0.097 µM) against HEp2 cells, while 2 exhibited moderate antiviral activity against RSV with IC50 = 4.20 µM (95% CI 3.31–5.33).

The Spirocyclic Imine from a Marine Benthic Dinoflagellate, Portimine, Is a Potent Anti-Human Immunodeficiency Virus Type 1 Therapeutic Lead Compound

“…A previous report also indicated that portimine has much lower toxicity than the other cyclic imine toxin [24]. In contrast, several studies reported that portimine exhibits toxicity in several cells in culture [25,26]. Similarly, in our study, portimine was toxic to peripheral blood mononuclear cells even at 1 nM (data not shown).…”

Synthetic Studies Towards Spirocyclic Imine Marine Toxins Using N-Acyl Iminium Ions as Dienophiles in Diels–Alder Reactions

“…Named after their common structural motif (shaded in blue, Figure 1), these toxins can be further classified by the size of the cyclic imine ring, with either 7,6-spirocyclic systems (as in the spirolides, e.g. spirolide A (1), pinnatoxins, and pteriatoxins) or 6,6-spirocyclic systems (as in gymnodimine A (2) and recently isolated kabirimine (3) 3 ) being the most common. 4 Portimine A (4), isolated in 2013, is an example of a cyclic imine toxin bearing a 5,6-spirocyclic imine system.…”

Synthesis of the C4–C16 Polyketide Fragment of Portimines A and B

“…Portimine A ( 1 ) was first isolated from the benthic marine microalga Vulcanodinium rugosum off the coast of New Zealand in 2013. It holds a special place in this family of natural products as the first natural product to be isolated that contains a five-membered cyclic spiroimine functionality. , Recently, portimine A ( 1 ) was reisolated independently by both the Strangman and Tanaka groups, along with a new derivative portimine B ( 2 ). Portimine B ( 2 ) possesses the same core scaffold as portimine A ( 1 ), except for the oxidation state at C5 and the hydrolyzed THF ring.…”