New Bisbenzylisoquinolines, Fatty Acid Amidic Aporphines, and a Protoberberine from Formosan Cocculus orbiculatus

Abstract

Two new bisbenzylisoquinoline alkaloids, (+)-coccuorbiculatine A (2) and (+)-10-hydroxyisotrilobine (3), two new amidic aporphines, a mixture of (+)-laurelliptinhexadecan-1-one (6) and (+)-laurelliptinoctadecan-1-one (7), and one new protoberberine (-)-4-methoxy-13,14-dihydrooxypalmatine (8) have been isolated from the stems of Taiwanese Cocculus orbiculatus. The structures were established on the basis of extensive analysis of spectroscopic data and by comparison with known related metabolites. Cytotoxicity of the isolated compounds was examined toward HepG2, Hep3B, MCF-7, and MDA-MB-231 cancer cell lines. Alkaloids 1 and (-)-sinococuline (9) showed significant inhibitory activity against the target cell lines.

A rare head–head binding pattern in bisbenzylisoquinoline alkaloids

“…Bisbenzylisoquinoline alkaloids having diaryl ether linkages at C-6, C-7 0 are rare. This head-head binding pattern has been previously observed in bisbenzylisoquinoline alkaloids having two head-head bridges between carbons C-7, C-8 0 and C-6, C-7 0 isolated from species belonging to the Menispermaceae (Chang & Wu, 2005) and Monimiaceae families (Schiff, 1997). Tabienine B is the second alkaloid presenting head-head binding between carbons C-6 and C-7 0 and is the second new alkaloid to be isolated from a species belonging to the Berberis Aequinoctiales subgroup (Chang & Wu, 2005;Quevedo et al, 2008).…”

Amide–Iminoate Isomerism in Antineuroinflammatory Isoquinoline Alkaloids from Stephania cepharantha

“…Based on the HMBC cross-peaks of C H 3 O-12 (δ H 3.89)/C-12 (δ C 147.3) and C H 3 O-6 (δ H 3.71)/C-6 (δ C 149.6), it was assumed that the two methoxy moieties in 5 were linked to C-12 and C-6. Additionally, the downfield shift of CH 3 O-12 (δ H 3.89) suggested that 5 was a bisbenzylisoquinoline alkaloid with both head-to-head and tail-to-tail linkages (chemical shift of CH 3 O-12 ranged from δ H 3.87 to 3.95). − The remaining signals of a methyl (δ H 2.66, 3H, s) and a formyl group (δ H 8.17, 1H, s) were attributed to CH 3 N-2′ and CHON-2 based on the HSQC (Figure S31, Supporting Information) and HMBC data. The chemical shift of CH 3 O-6 at δ H 3.71 as well as previous studies indicated that the absolute configuration of compound 5 was either (1 R ,1′ S ) or (1 S ,1′ R ) .…”

Recent Strategies for the Synthesis of Protoberberines and Protoberberine Type Compounds

“…After selective O-and subsequent N-methylation affording (S)-coclaurine (14) and (S)-N-methylcoclaurine (15) followed by the hydroxylation of the benzyl moiety to give (3'S)-hydroxy-N-methylcoclaurine (16), the 4'-hydroxy-group is methylated resulting in the central intermediate of benzylisoquinoline alkaloid biosynthesis, (S)-reticuline (17). Finally, ring C of the protoberberine core is completed by oxidation of the N-methyl group of (S)-reticuline (17) with the berberine bridge enzyme leading to (S)-scoulerine (18), which then is transformed via canadine (19) to berberine (20) [12] (Scheme 1).…”