Corynantheine synthesis

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. 

The first total synthesis of ( )-dihydrocorynantheine (54) (163) and ( )-corynantheine (52) (164) with normal stereo arrangement of the C-3, C-15, and C-20 hydrogens (a, 3, a, respectively) was published in full detail by van Tamelen and co-workers in 1969. [In preliminary form it has been published earlier (165, 166).]... 

On the other hand, ( )-corynantheine was achieved from key intermediate 301, used previously in the synthesis of ajmaline (167). The fra/u-tosylhydrazone derivative 302 afforded the desired vinyl-substituted indolo[2,3-o]quinolizine 304 in moderate yield along with the corresponding ethylidene-substituted isomer. Formylation and methylation of 304 afforded finally ( )-corynantheine (164). 

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

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. 

Intramolecular ene reactions can be highly diastereoselective 401,41fM116 An example is provided by the synthesis of the corynantheine derivative 14 (Scheme 26.16)410... 

The hydrogen atoms at C-15 and C-20 in rhynchophylline are thus oriented trans with respect to each other, a conclusion which is amply confirmed by the partial synthesis of rhynchophylline from dihydro-corynantheine (XXXII) (66). Reaction of XXXII with tertiary butyl hypochlorite gave the chloroindolenine derivative XXXIII, which on methanolysis was converted into the imidoether XXXIV. Hydrolysis of XXXIV with refluxing aqueous acetic acid then gave rhynchophylline. 

In connection with the development of a partial synthesis of heteroyohimbine alkaloids from corynantheine (109), thereby obviating a possibly troublesome... 

The attempts by the same investigators to realize the synthesis of ajmalicine from corynantheine derivatives, previously reported" in brief, have now been published in detail " thus, while oxymercuration of demethylcorynantheine (115) followed by NaBHt reduction gave small quantities of ajmalicine (80) and 19-epiajmalicine, the major product was the IS-abeo (17 16) yohimbane derivative (116). 

Takano et a]L. have extended their syntheses of corynantheine relatives from ( )-norcamphor, and have completed the synthesis of the 18,19-dihydro-alkaloids with all four stereochemical conflg-... 

Autrey and Scullard used this fragmentation in a synthesis of corynantheine... 

Autrey and Scullard used this fragmentation in a synthesis of corynantheine (11) from yohimban-l7-one (7). The synthesis also involved a novel desulfurization of the enol thioether (9) without reduction of the vinyl group. This step... 

A partial synthesis of natural (3/S,15j8,20i )-corynantheine involving an interesting ring cleavage of yohimbone has been published (67). 

In the first slide I summarized what I am going to talk today, the list of target indole alkaloids. My talk consists of two parts, the first part is on the synthesis of yohimbine and its group and the second part on the synthesis of corynantheine and heteroyohimbine types of alkaloids. 

In conclusion of this part of synthesis, usefulness of enamide prepared from harmalane with 3-furoyl chloride was firmly demonstated by its application to the synthesis of relatively untouched alkaloids of corynantheine group of alkaloids. Actually, we have succeeded in the synthesis of geissoschizine and hirsu-teine, thereby extended to the formal synthesis of corynantheine and hirsutine. Further, unexploited alkaloids rhazimanine and isositsirikine were also synthesized, thereby shed light on the chemistry of these groups of alkaloids. Full clarification of the problems on their structures will be achieved. 

A synthesis of acetomycin 35, together with three stereoisomers, has been achieved using the D-glucose-based precursor 34.22 yhe known branched glycoside 36 has been used in the synthesis of lactone 37 which has then been used, via a Pictet-Spengler cyclocondensation with trytamine, in a new approach to the corynantheine and heteroyohimbine classes of indole... 

The enamine (/dienamine)-iminium cycle-specific cascade catalysis is an important constituent of amine-catalyzed cascade reactions [10]. This strategy has been explored extensively and also applied to natural product synthesis. One such example is the total synthesis of dihydrocorynantheol, which was first isolated from the bark of Aspidosperma marcgravianum in 1967 [29]. This indole alkaloid is a member of the corynantheine and was found to exhibit antiparasitic, antiviral, or analgetic activities, which have attracted considerable attention from the synthetic community. Among those reported total syntheses, Itoh et al. developed a Mannich-Michael cascade reaction catalyzed by L-proline 52 for the total synthesis of ent-dihydrocorynantheol 54 (Scheme 3.8) [30], The cascade reaction of 3-ethyl-3-buten-2-one 51 with dihydro-P-carboline 50 catalyzed by 30mol% of (S)-proline afforded the tetracyclic core structure 53 in 85% yield. Excellent stereoselectivity was achieved in this cascade reaction (99% enantiomeric excess and almost complete diastereomeric control). Therefore, this organocascade reaction could lead expeditiously to construction of the core structure, which enabled the authors to accomplish the total synthesis of enl-dihydrocorynantheol 54 in just five steps. 

In a biogenetically patterned synthesis of oV-corynantheine carried out by van Tamelen and Wright, the essential features of the alkaloid have been assembled at the very outset and incorporated into the key tetracyclic intermediate (A) previously utilized for the synthesis of ajmalicine. ... 

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