Corynane

The structural formula of aspexcine, isolated first from Aspidosperma excel-sum Benth. and identified as a 10-methoxyisositsirikine (4), had to be corrected. Recently, Verpoorte et al. (53) established that, instead of a corynane skeleton, aspexcine has a 10-methoxy, normal yohimbane structure. 

Adirubine (66), the first member of a new series of 5p-carboxy alkaloids having a corynane skeleton, has been isolated from Adina rubescens by Brown et al. (60). The first structure elucidation of adirubine, based on spectral data only, was incomplete (60). Final determination of the steric arrangement around ring D was performed by correlation with 5 p-methoxycarbonyldihydromancunine, and it proved to be alio (3a, 15a, 20a) (67). 

It has been possible to correlate yohimbine with the corynane group by opening ring E (5). The reduction product (XI) of yohimbone (IX) with sodium borohydride was converted as shown to the corresponding chloride (XII). Elimination of hydrogen chloride from this and oxidation of the unsaturated base (XIII) yielded a dialdehyde (XIV) whose bis-semicarbazone on reduction with hydrazine gave dihydrocorynantheane (XV), the absolute configuration of which had already been established (Vol. 7, p. 37). 

Mimblne and Corynanthine. Isomeric indole alka->iids known as the yohimbanes exhibit different degrees of declivity toward the ap and o 2-adrenergic receptors, depending on their stereochemistry. For example, yohimbine Is d selective antagonist of the or, receptor, while corynan-... 

In the partial synthesis of Khuong-Huu and co-workers (205), corynan-theidine (105) was reduced with NaBFL, in the presence of trifluoroacetic acid (TFA) to the corresponding 2a,7a-dihydro derivative 106, which by NaOMe/MeOH treatment was transformed to the corresponding acetal 107. Benzenesulfonylation of compound 107 afforded compound 108. Photosensitized oxidation of 108 in the presence of rose bengal and KCN yielded compound 109, which, via the corresponding iminium ion, was claimed to cyclize to Afa-benzenesulfonyl-2a,7a,19,20a-tetrahydro-10-de-soxysarpagine (110) (a dihydroindole derivative, which, however, could not be transformed to an indole derivative) (Scheme 6). It is noteworthy that... 

The tetracyclic oxindole alkaloids possess four asymmetric centers (C-3, C-7, C-15, and C-20) and therefore can exist as sixteen possible diastereoisomers. However, since all naturally occurring indole alkaloids of the corynane type possess a C-15a hydrogen [17), the total number of isomers is restricted to eight. Taking into consideration the asymmetric... 

Geissospermine. (t6R,l9E)-l9,20-Didehydro-[6- (lQptt) 2l )-23-deoxy-2JI 22 dihydro-If-oxa"12t 14-seco-strych nidin-I Q-ylJcarynan 17-oic acid methyl ester 19 20 didehydro-16-(15-ethyl-3at f a 7t8.l3a-hexahydro-4H-4r6-ethan o-lH,3H [l,3Joxa zino[S,4y 5 1 mJpyrrolof2,3-dJca rbazol-l-yl)-corynan-l7-oic acid methyl ester 0,l7-epoxy- t-(3-ethylidene-1,2,3,4,6,7.12, I2b-octahydroindole[2,3-a]quinol-izin -2 -y0-curan-1 -propanoic acid methyl ester. 

The synthetic scheme used by Woodward in his famous reserpine synthesis has been adapted for a synthesis of racemic apoyohimbine (Chart IV). The aldehyde LIXa, precursor of rings D-E of apoyohimbine, was prepared together with its epimer (LIXb) by 0s04/Ba(C103)2 oxidation of the key intermediate (LVIII) (cf. reserpine synthesis. Volume VIII, p. 316). Condensation of LIXa with tryptamine, followed by the conventional steps, yielded the racemic lactone LXIV, which was subsequently hydrolyzed and esterified to LXV, isomeric with corynan-thine. Racemic apoyohimbine (LXVI) was then secured by tosylation of LXV followed by basic treatment of the 18-tosylate (39a). 

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. 

In this section are described the syntheses of some simple indolo-[2,3-a]quinolizine derivatives which bear a close relationship to the alkaloids of the yohimbane and corynane groups. 

Eburnan—Corynanfbe-Type Alkaloids Strychnos-Strychnos-Jype Alkaloids Coiynanthe-Strychnos-Jype Alkaloids Aspidospermatan—Aspidospermatan-Type Alkaloids Co/ynanf/ie—Aspidospermatan-Type Alkaloids Cory nan the—Corynan fbe-Ty pe Al ka loid s... 

---