Corynantheine, derivatives

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 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). 

The indole derivative corynantheine is iV-methylated by diazomethane in ether. ... 

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 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. 

The pair corynantheine-corynantheidine plays an important role in that a number of alkaloids of other structural types can be transformed into derivatives of either of this pair. The configuration a of C-15,H can thus be assigned to ajmaline (CXIII) because it can be transformed into two isomers of CXV, one of which on further transformation yields a tetracyclic derivative (CXV) related to corynantheidine (75). The same sequence of reactions applied to isoajmaline (epimeric at C-20 with ajmaline) gives a derivative of corynantheine (75). Sarpagine (CXVI)... 

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... 

Monoterpene Bases.—Yohimbine-Corynantheine (and Related Oxindoles)-Pier aline Group. It is well known that 3,4-dehydroyohimbane (35a) is reduced by zinc-acetic acid to a mixture of yohimbane (35c) and i/ -yohimbane (35d) however, when 10-methoxy-3,4-dehydroyohimbane (35b) was similarly treated, a 2,3,4,7-tetrahydro-derivative (17 % yield) was formed as well as the corresponding 10-methoxy-yohimbanes. It was shown that this did not arise by further reduction of either of the methoxy-yohimbanes and no explanation is yet available for this interesting difference. Reserpine, a 6-methoxyindole, underwent C(3)-N(4) bond fission on reaction with zinc-acetic acid, as did indoles with no ring A methoxy-group. Cleavage of the C(3)-N(4) bond with the formation of N(4)-cyano-C(3)-alkoxy- or hydroxy-seco-derivatives was observed when yohimbine, i/ -yohimbine, and methyl reserpate were subjected to von Braun degradation conditions in alcohol or aqueous solution. 

Monoterpenoid Alkaloids.—Corynantheine-Heteroyohimbine-Yohimbine Group, and Related Oxindoles. The first recorded extraction of the leaves and twigs of Peschiera laeta Mart, has yielded geissoschizol, a base not previously found in the Peschiera genus. Antirhine and, to a lesser extent, its quaternary Nb-metho-derivative, occur in the bark of Strychnos camptoneura Gilg. et Busse and in Amsonia elliptica, which also contains tetrahydrosecamine, pleiocarpamine,... 

When these stereochemical results were applied to vincoside, the indolic analog of deacetylipecoside and its C-3 epimer, strictosidine, which had been correlated chemically with corynantheine and antirhine (Section IV,A), conflicting results were obtained. They cast serious doubt on the validity of the previous assignment and indicated that inversion of C-5 must have occurred at some stage in the chemical operations. An independent X-ray crystallographic study of 0,0-dimethylipecoside was therefore undertaken. The results obtained confirmed in detail the structure and absolute stereochemistry derived chemically, except that the hydrogen atom at C-5 should have a (i configuration (13). 

Several syntheses of corynane derivatives have been reported in the recent literature. dZ-Corynantheine has been totally synthesized by van Tamelen s group (44) (Chart VI). The key intermediate, LXXIII, obtained by a biogenetic type of interaction of tryptamine, formaldehyde and the ketoester LXXII, was converted in four steps to an isomeric mixture (15,2.0- ra9 s/c s-isomers) of the tetracyclic ketoester LXXIVa,b. 

Ch. 2 Alkaloids Derived from Tiyptamine and an Unrearranged Monoterpene Unit Ch. 3 The Corynantheine-Heteroyohimbine Group Ch. 4 The Yohimbine Group... 

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