Crinine from Amaryllidaceae

Previous studies45 have demonstrated that tyrosine and phenylalanine follow separate pathways in providing the hydroaromatic C6—C2—N unit and the aromatic C6 unit of mesembrine. In this respect mesembrine follows the pattern, already established for the biosynthesis of the structurally related Amaryllidaceae alkaloids derived from O-methylnorbelladine, e.g. haemanthamine (70). The present investigation46 followed this lead and started with a reasonable working hypothesis (Scheme 12) in which the biosynthesis proceeds via O-methylnor-belladine (68) and intermediates of the crinine type such as (75). However, feeding... 

The tandem aza-Cope/Mannich cyclization methodology has been used as a central step in the synthesis of the Amaryllidaceae alkaloid ( + )-crinine starting from 191137. 

Some Amaryllidaceae plants possess a group of alkaloids containing a Cg— C2-N-C1-C6 unit. In this unit, the C6-C2-N moiety is derived from tyrosine or tyramine, and the C -Ci part is derived from phenylalanine through cinnamic acid, p-coumaric acid, and protocatechualdehyde [1]. Tyramine (C6-C2-N unit) and protocatechualdehyde (C -Ci unit) are then combined and methylated to form O-methylnorbelladine, which is a common biosynthetic precursor of various Amaryllidaceae alkaloids. Through para,ortho -, ortho,para - and para,paw-phenol coupling of norbel-ladine, the lycorine, galanthamine, and crinine type alkaloids are formed, respectively [2]. 

Lastly, norbelladine (top of Scheme 1.7) is issued from the reductive amination of 3,4-dihydroxybenzaldehyde (derived from phenylalanine) with tyramine (derived from tyrosine) and constitutes a biosynthetic node leading to Amaryllidaceae alkaloids such as galantamine, crinine, or lycorine depending on the topology of phenolic couplings. In all these biosynthetic routes, radical phenolic couplings are key reactions for C—C and C—O bond formations and rearrangements [30, 31]. 

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