Crystal Structure of (−)‐Corycavinium (+)‐10‐Camphorsulfonate, a biosynthetic intermediate to hexahydrobenzo[c]phenanthridine alkaloids

Abstract

The crystal structure of (-)-corycavinium (+)-10-camphorsulfonate has been investigated by X-ray analysis. The structure of (-)-corycavinium ion ( = (-)-(7S,l3S,\4R)-5,6,13,13a-tetrahydro-l3a-hydroxy-7-methyl-2,3;9,10-bis(methylenedioxy)-8//-dibenzo[a,g]quinolizinium), has been determined. The conformation with B/Ccis -conjunction, a twisted half-chair of ring B, and a half-chair of ring C, as well as a -oriented substituted groups N-Me, C •Me, and C-OH is revealed. Feeding experiments with cell suspension cultures of Corydalis incisa (Papaveraceae) defined the intermediacy of (-)-corycavinium in the route from protoberberine-type to hexahydrobenzo[c]phenanthridine-type of alkaloids. On the basis of the present crystal conformation, the stereospecificity of the relating enzyme is biogenetically considered.Introduction. -Since 1867, there have been chemical studies [1] of protopine-type alkaloids, produced by all papaveraceae spp., with contemporary efforts focussed on this group's biosynthetical behavior [2][3][4][5]. Protopine-type alkaloids function as key intermediates in the metabolism of the protoberberine type (Scheme 1).The structural formulas of protopine-type alkaloids are commonly described as 'free base form (a)' in which ring B is a ten-membered ring with a tertiary N-atom. They are so-called, because this type of alkaloids are conventionally isolated under conditions of a strongly alkaline solution from an extract of papaveraceae plants. Though the chemically isolated form of this type alkaloid is the tertiary free-base form a, the quarternary form may be essential under the living-cell condition, the presence of free base form a being impossible in the cytoplasm of a plant cell, owing to its poor solubility. Three forms are possible structures for the quarternary form of protopine-type alkaloids; i.e., protonated type 'protonated form (b)', eis -ring-closure type 'protopinium form (c cis )\ and trans -ringclosure type 'protopinium form (c trans y.Although use of spectroscopic methods such as CD, IR, and NMR has been proven for the conformational study of the tertiary-amine form of alkaloids, it is not so useful for the quarternary amine form, when it is the salt of protopine-type alkaloids. This problem may be due to the use of polar solvents in measuring the spectra of the structures possessing the ionic bonding. Consequently, while the importance of protopine-type alkaloids is now well known, studies involving the protopinium form, which give a well-defined conclusion, are limited to the use of X-ray analysis [6].

Conformational Features of 7,8,13β,14α‐Tetrahydro‐N7‐methylcorysaminium, a biosynthetic intermediate to the protopine‐type alkaloid corycavine

“…3 ) . Ring B is much more distorted than ring C. A similar 'anti-cis' quinolizidinium conformation was also observed for 4a [7].…”

“…To elucidate the biosynthetic route to isoquinoline alkaloids [7], we have provided data on the configurational problems on the substrate side.…”

“…The (*)-7,8,1%,14a -tetrahydr~-N~-('~C)methyIcorysaminium iodide (I3C-3a. I) was prepared according the [7], and the single crystals for X-ray studies were crystallized as brownish columns from MeOH at r.t.…”

“…Since the relative configuration at N(7), C(13), and C(14) of the (&)-form 3a was determined by the above X-ray analysis, the absolute configuration of the (-)-form (-)-3 can be deduced to be (7S,13S,14S) by chemical correlation of (-)-3a with (-)-(7S, 13S, 14R)-corycavinium (4a) [7] (Scheme). This agrees with our previous CD spectral result [6].…”

“…Why the structure of 3a takes an 'anti-cis' conformation, but not a 'syn-cis' one can be explained by considering 1 ) the steric repulsion between the bonds H-C( 1) and H-C ( 13) and between H,,-C(5) and H,,-C(8) and 2) the energetically unfavorable axial orientations of Me-N (7) and Me-C(13) in the 'syn-cis' conformation.…”