Corynantheine alkaloids

A new pleiocatpine derivative, 12-methoxypleiocarpine (222) was obtained from Kopsia griffilhii [58]. This plant furnished a diverse array of alkaloidal types which included the p-carboline compounds, harmane (55) and harmicine (56), the corynantheine alkaloids, tetrahydroalstonine and 16(R)-19,20- -isositsirikine 221, the aspidofractinine alkaloids, kopsilongine (223), kopsamine (224), kopsamine-Moxide, pleiocarpine (221), kopsinine (220), fV(l)-ntcthoxycarbonyl-12-melhoxy-A -kopsinine (216), -carbomethoxy-1 l-hydroxy-I2-methoxykopsinaline (225), Mcarboinethoxy-ll,12-dimethoxykopsinaline (226), the rare... 

Hirsutfaife). A name used for four different compounds a) l-isothiocyanato-8-(methylsulfinyl)oc-tane, see mustard oils. - b) A corynantheine alkaloid fmm Mitragyna and Uncaria species, C22H28N2O3, Mr 368.48, cryst., mp. 101 °C, [aJu +68.6° (CHCI3). The... 

Corynantheidine, C22H28O3N2. This isomeride of corynantheine was found by Janot and Goutarel (1944) in the residual, benzene-soluble alkaloids of Pseudocinchona africana. It was isolated as the picrate, m.p. 252°, — 152° (acetone). The base, B. COMe2, had m.p. 117°,... 

Two important books on the biogenesis of indole alkaloids have been published (5, 6), therefore we do not intend to cover the literature of the biogenesis of corynantheine- and yohimbine-type alkaloids. Our chapter begins with the structure elucidation of the alkaloids isolated during the past two decades and proceeds with the synthesis, transformation, as well as spectroscopy of the alkaloids in question. 

Similarly to the corynantheine-type alkaloids, yohimbines could also be divided into four groups according to the relative configurations of the stereo centers C-3, C-15, and C-20. 

The synthesis of corynantheine-type alkaloids along a biogenetic route has been widely investigated by Brown et al. (175, 176). 

An interesting transformation was discovered by Sakai and Shinma (181) during the chemical investigation of corynanthe alkaloid (V-oxides. Polonovski reaction and sodium cyanoborohydride reduction of hirsuteine A-oxide (331) gave corynantheine (52) and 3-isocorynantheidine (65), the latter likely formed by reduction of the conjugated iminium intermediate 334. 

It has been shown that CD measurement is a proper tool to determine the absolute configuration of the C-3 stereo center in corynantheine and yohimbine alkaloids (300). The chiroptical properties of stereoisomeric yohimbanes and 17-ketoyohimbanes also have been studied. Cotton effects due to aromatic and ketone absorptions have been considered in terms of the appropriate sector and... 

Invention of Fourier transform instruments and consequent development of 13C-NMR techniques have supplied the chemist with excellent tools in characterizing complex molecules and making fine stereochemical distinctions. During the last two decades following the fundamental work of Wenkert (130, 228, 308), substantial amounts of l3C-NMR data of corynantheine and yohimbine alkaloids have been published. Some numerical values of interest are cited in Tables VIII, IX, X, and XI. 

Configuration and conformation, elucidation by X-ray diffraction, 22, 51 (1983) Corynantheine, yohimbine, and related alkaloids, 27, 131 (1986)... 

Consistently high levels of asymmetric induction have been achieved in the alkylation of tetrahydroisoquinolines using this methodology, as is demonstrated in the synthesis of chiral isoquinolinium alkaloids, e.g., (-)-salsolidine (61% yield, 95% ee)13, ( + )-homolaudanosine (48% yield, 96% op)14, ( —)-norcoralydine (37% yield, 98.5% op)15, some ben-zo[ ]quinolizidines (>99%ee), precursors of natural emetine16, corynantheine alkaloids17 and some azasteroids (93% ee)18. 

Studies with corynantheine-type oxindole alkaloids have also been conducted [48]. Since rhynchophylline (68) and isorhynchophylline (69), Fig. (17), have an H-15 and H-20 trans relationship, epimerization would be expected to occur only at C-7. And indeed, this proved to be the case acetic acid treatment yielded a ratio of 70 30 (68 69). Even though... 

Hirsutine (85) is a corynantheine-type indole alkaloid with a C/D cis ring juncture (pseudo stereochemistry). This compound has recently been found to exhibit highly potent inhibition of the replication of the strains of influenza A (subtype H3N2) [63]. The EC50 of hirsutine was 11- to 20-fold more potent than that of the clinically used ribavirin. Exploration of the important structural features of this molecule revealed that the stereochemistry at C-3 (.R) and C-20 (R) as well as the presence of the Nb lone pair were essential for the anti-influenza A activity. Thus, the C-3 epimer, dihydrocorynantheine (86) (normal stereochemistry), was much less active than hirsutine (85). 

The indole alkaloids of Mitragyna hirsuta Havil, M.javanica Koord. et Val. var. microphylla Craib, M. speciosa, and Nauclea coadunata are mostly in the corynantheine-heteroyohimbine-yohimbine group. The alkaloids isolated from the leaves of Mitragyna hirsuta have been identified as hirsutine, rhynchophylline, isorhynchophylline, mitraphylline, isomi-... 

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