The Isolation and Characterization of a New Tetrahydroprotoberberine Alkaloid from Corydalis clarkei

Abstract

The MeOH extract of Corydalis clarkei Prain yielded two tetrahydroprotoberberine alkaloids that bear the unusual 1,2- and 9, 10-tetraoxygenated substitution pattern observed previously only in caseanidine . The alkaloids have been identified as caseanidine (1) and the new alkaloid, clarkeanidine (2). The 1H- and 13C-nmr shifts of both alkaloids have been assigned unambiguously using 2-D nmr. The elucidation of the structure of 2 was achieved by comparison of the 1H- and 13C-nmr spectra of 2 with those of caseanidine coupled with additional spectroscopic evidence.

Characterization and Mechanism of the Berberine Bridge Enzyme, a Covalently Flavinylated Oxidase of Benzophenanthridine Alkaloid Biosynthesis in Plants

“…The substitution pattern of the aromatic ring moiety of the isoquinoline nucleus appears to be irrelevant since (S)-protosinomenine with the 6-hydroxy 7-methoxy substitution pattern and crassifoline with the 7-methoxy 8-hydroxy substitution pattern were both converted. This latter result has an implication in the biosynthesis of the protoberberine alkaloids clarkeanidine (25) and caseamine (26) that contain the crassifoline substitution pattern (27). Since crassifoline is readily converted to the corresponding protoberberine, it can be expected that the berberine bridge enzyme found in plant species such as Corydalis (2) should be involved in the biosynthesis of both 6,7-substituted (reticuline-derived) and 7,8-substituted (crassifoline-derived) protoberberine alkaloids.…”

Establishment of a search library about benzylisoquinoline alkaloids based on selective separation on the binaphthyl column and standard analysis on C18 column

“…Quick structure proposal can be realized by using liquid chromatography coupled with tandem mass spectrometry (LC‐MS/MS) method, but not accurate, even though this method has been widely used for rapid chemical identification in the field of natural products . Hence, it is necessary to isolate the compounds from herbal medicines in many cases . However, this approach is time‐consuming, laborious, and difficult.…”

“…even though this method has been widely used for rapid chemical identification in the field of natural products [5,6]. Hence, it is necessary to isolate the compounds from herbal medicines in many cases [7,8]. However, this approach is time-consuming, laborious, and difficult.…”

Total Synthesis of the Ortho-Hydroxylated Protoberberines (S)-Govaniadine, (S)-Caseamine, and (S)-Clarkeanidine via a Solvent-Directed Pictet–Spengler Reaction

“…Norcrassifoline ( 23 ) was also used as the synthetic precursor for the related protoberberines caseamine ( 24 18 ), displaying activity against urease, 11 and clarkeanidine ( 25 19 ). Biosynthetically, the ring closure of 1-benzyltetrahydroisoquinolines to tetrahydroprotoberberines does not proceed with formaldehyde but via the berberine bridging enzyme (BBE) catalyzed oxidation of N -methylated benzyltetrahydroisoquinolines, immediately followed by ring closure of the intermediate methylene iminium salt (Scheme 5).…”

“…Clarkeanidine ( 25 ): mp 177–180 °C (recrystallized from DCM/petroleum ether), (lit. 19 mp 178–179 °C); ee 95% (Chiralcel AD column, eluent n -heptane/2-propanol 70:30, flow 1.000 mL/min); [α] D 20 −442 ( c = 0.1, CHCl 3 ) [lit. 17,18 [α] D 20 −277 (CHCl 3 )]; 1 H NMR (300 MHz, CDCl 3 ) δ 6.75 (m, 2H), 6.66 (m, 2H), 5.78 (bs, 2H), 4.24 (d, J = 16.0 Hz, 1H), 3.99 (dd, J = 11.2, 3.5 Hz, 1H), 3.90 (s, 3H), 3.89 (s, 3H), 3.84 (d, J = 16.0 Hz, 1H), 3.72 (dd, J = 16.2, 3.6 Hz, 1H), 3.22–3.12 (m, 1H), 3.12–3.00 (m, 1H), 2.89–2.64 (m, 3H); 13 C{ 1 H} NMR(75 MHz, CDCl 3 ) δ 144.3, 143.8, 142.5, 141.7, 129.0, 128.8, 124.6, 121.0, 119.4, 108.9, 56.2, 56.2, 56.1, 53.0, 49.1, 32.2, 29.8; HRMS (FD + ) m / z calcd for C 19 H 22 NO 4 (M + H) + 328.1549, found 328.1558.…”