C₁₉ Benzylisoquinoline Alkaloid with Unprecedented Architecture from Hypecoum erectum

Abstract

Hyperectumine (1), the first C19 benzylisoquinoline alkaloid with a complicated ring system, was isolated from Hypecoum erectum and structurally characterized. Its biosynthetic origin should involve a hybrid pattern of C8 + C8 + C1 + C2, from which a C17 benzylisoquinoline alkaloid might be further attacked by a malonamic acid and undergo decarboxylation and cyclization to produce 1. Compound (−)-1 exhibited moderate anti-inflammatory activity via suppression of LPS-activated inflammatory mediators in RAW 264.7 macrophage cells.

Hypecoum spp.—Chemistry and Biological Activity of Alkaloids

“…glaucescens, H. imberbe, H. lactiflorum, H. pendulum, H. trilobum, H. leptocarpum, H. erectum, H. ponticum and H. parviflorum. Based on their structures, the Hypecoum alkaloids can be divided into eight major groups: protopines (1-11), protoberberines (12)(13)(14)(15)(16)(17), benzophenantridines (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28), aporphines (29)(30)(31)(32)(33), simple isoquinolines (34)(35)(36)(37)(38), secoberbines , spirobenzilisoquinolines (67)(68)(69)(70)(71)(72)(73) and others (74-86). Two chemical structures have been detected in the literature with the name leptocarpine-protopine alkaloid 8 and alkaloid 82.…”

“…Eleven benzophenantridine alkaloids (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) have been identified in six Hypecoum species-H. procumbens, H. leptocarpum, H. trilobum, H. ponticum, H. imberbe and H. erectum (Table 2). Their structure includes a tetracyclic skeleton with an aromatic (18, 19, 21 and 28) or nonaromatic (20,(22)(23)(24)(25)(26)(27) ring B.…”

“…Eleven benzophenantridine alkaloids (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) have been identified in six Hypecoum species-H. procumbens, H. leptocarpum, H. trilobum, H. ponticum, H. imberbe and H. erectum (Table 2). Their structure includes a tetracyclic skeleton with an aromatic (18, 19, 21 and 28) or nonaromatic (20,(22)(23)(24)(25)(26)(27) ring B. The alkaloids with three aromatic ring systems are usually in the form of quaternary ammonium salts (18,19,21), and those with non-aromatic ring B are usually C-8-substituted (23)(24)(25)(26)(27).…”

“…In recent years, more than 40 alkaloids have been identified in Hypecoum species, and new alkaloid structures, along with their pharmacological activities, are reported every year, enriching the diversity of natural compounds. Some of them have promising properties for the treatment of important diseases such as inflammation, cancer and microbial infections [18,19,22,23,[26][27][28][29].…”

Hypeisoxazole A, a Racemic Pair of Tetrahydroisoxazole-Fused Benzylisoquinoline Alkaloids from Hypecoum erectum and Structural Revision of Hypecoleptopine

“…Briefly, the C 17 BIA (intermediate A) which is derived from the amino acid precursor l -tyrosine would be the precursor of 1 and 2 , and the amino acid asparagine and its deaminate derivative (fumaramic acid) would play an important role in the construction of ring F of 1 and rings C and D of 2 . In the biosynthesis of 1 , the C 17 spiro-BIA intermediate B is produced from intermediate A by Stevens rearrangement, which further combines with asparagine and then undergoes a series of dehydration and dehydrogenation steps to produce the key intermediate B-1. , Oxidation of B then yields B-2, which forms the fleeting intermediate B-3 by β-elimination of a tertiary amine N -oxide and in situ hydroxylamine oxidation . Finally, compound 1 can be formed from the nitrone-alkene 1,3-dipolar cycloaddition of B-3 .…”