Cherylline

Some novel additions to this family of alkaloids include ryllistine (579), the first 4-oxygenated norbelline alkaloid (6) augustamine (582) (26) latifine (594), a biogenetic isomer of cherylline (595) (221) the O-glycosyl alkaloids lycorine-... 

Several efficient syntheses of ( )-cherylline (595) have been reported, and the common strategic feature of these entries is the cyclization of p-quinonemethides or functional equivalents thereof (223-225). For example, reaction of 609, which was readily accessible from 4-benzyloxystyrene by sequential reaction with bromine and methanol, with 3-benzyloxy-4-methoxy-(V-methylbenzylamine gave the tertiary amine 611 (223). In related work, 611 was obtained via ami-nolysis of the mesylate 610 that was prepared in two straightforward steps from 4-benzyloxystyrene oxide (224). When 611 was heated in strong acid, cycliza-... 

A more concise route to ( )-cherylline was also devised and commenced with the reductive animation of isovanillin with methylamine followed by reaction of the intermediate benzylamine with vinyl triphenylphosphonium bromide to provide the aminophosphonium salt 619. Sequential treatment of 619 with n-butyllithium and the quinone ketal 615 followed by reaction of the resulting crude allylic amine 620 with boron trifluoride etherate gave the phenolic amine 618 in good overall yield (225). 

Structurally, the most relevant innovations are represented by the isolation from Crinum spp. of cherylline (332), possessing a new C15 skeleton, and by the observation that tazettine (240) and related alkaloids are extraction artifacts arising from base-catalyzed isomerization of the corresponding [2]benzopyrano[3,4-c]indole derivatives. The uncertainties relating to most of the alkaloids reported in Volume XI, p. 384, still remain. 

Confirmation in favor of the assigned stereochemistry arose from X-ray analysis of cherylline-iV-p-bromobenzoate (72). 

Experimentally, it has been shown that 344 (R3 = Me) cyclizes readily on basic treatment to racemic cherylline and under a variety of conditions 75). 

Dimethylcherylline, dimethylether of alkaloid cherylline, has been prepared (15% total yield) from the appropriately substituted /V-methyI benzamide, via condensation with the corresponding benzaldehyde and subsequent cyclization.137,152... 

Cherylline-type alkaloids derived from tetrahydroisoquinoline Narciclasine-type alklaloids and... 

The majority of the alkaloids that had affinity to the serotonin transporter (SERT) were crinine-type alkaloids. However, cherylline 4, tazettine 8 and 1-0-acetyllycorine 53 are the only alkaloids that showed affinity to SERT among the cheiylline-, tazettine- and lycorine-type alkaloids, respectively (80). The activity of the crinine-type alkaloids was attributed to the presence of a 1,3-dioxole moiety in common with the chnically used SSRI paroxetin (79). 

A new 4-arylisoquinoline alkaloid, latifine, isolated from Crinum latifolium, has been identified as an isomer (21, R = OH, R =H) of cherylline (21, R =H, R =0H) (S. Kobayashi, T. Tokomuto and Z. Taira, Chem.Comm., 1984, 1043). A novel synthesis of cherylline has been achieved from the iminium salt (19) by treatment with diazomethane, cyclisation of the resulting aziridinium salt (20) and hydrogenolytic removal of the benzyl groups (T. Kametani, et al., J.chem.Soc., Perkin I, 1982, 2935. 

Regarding synthetic studies, the syntheses of ( )-latifine (437) (200), of ( )-cherylline (440) and ( )-latifine (437) (201), and of ( )-0,0-dimethylcherylline (445) and ( )-6>,0-dimethyllatifine (446) (202) have been performed using the Pomeranz-Fritsch-type cyclization (Scheme 51), the Bischler-Napieralski-type reaction (Scheme 52), and intramolecular nucleophilic addition of aryllithium (generated by butyllithium) to a carbonyl group (Scheme 53). 

A newly discovered alkaloid, cherylline, has been shown to have a novel structure (5) derived from 4-phenylisoquinoline. It has been synthesised from the appropriate benzophenone by way of the alcohol, chloride, nitrile, and primary amine, followed by formylation, isoquinoline ring closure, reduction, and methylation. ... 

Apart from the accepted structural types of this class, this report will be concerned with the mesembrane group (26), miniatine (24), and cherylline (25) because of their obvious biogenetic relationship. 

Cherylline (25) is a new example of a 4-phenyl-1,2,3,4-tetrahydroisoquinoline alkaloid isolated from Amaryllidaceae plants. Description of its complete... 

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