The Condylocarpine Group

The isolation of 3-ethylpiperidine by the zinc dust distillation of aspidospermatidine and deacetylaspidospermatine made it probable that the m/e 136 peak derived from a piperidine ring incorporated in the aliphatic part of the molecule. An ideal model compound, dihydro-decarbomethoxyakuammicine (CCII, mol. wt. 266) was known (19). Its 

The fragmentation pattern proposed for alkaloids of this skeleton has been confirmed by the observation that spermostrychnine (CCXI) and its deacetyl derivative (CCXII) (21), as well as numerous other derivatives of the same basic skeleton substituted in positions 14, 16, and 20 (see following sections and Ref. 115a), fragment in the same way. In many cases the structures of these compounds have been proved independent of mass spectrometry. An exception to the normal breakdown pattern is seen in strychanone (CCXLIV) in which the 16-carbonyl group 

Stemmadenine (CCXIII) was first isolated from Stemmadenia donnell-smithii (8), where it occurs with (+ )-quebrachamine (I) and some iboga-type bases. Subsequently, it has also been found in Diplorrhyncus condylocarpon ssp. mossambicensis, where it occurs together with condylocarpine (CCXV), normacusine-B (Section VIII, B), two yohimbines, norfluorocurarine, and mossambine (Section VI, B and C, Ref. 116). 

Analysis and mass spectral molecular weight determination established the empirical formula, C21H26N2O3, for stemmadenine (8, 116, 117). Its UV-spectrum was characteristic of an indole (cf. ref. 55), while the IR-spectrum indicated the presence of a normal ester grouping (1718 cm-1) and the absence of any substituent in the indole aromatic ring (116). These findings were fully borne out by NMR-spectroscopy which showed the presence of an indole NH (9.3 S), four aromatic protons, and a carbo-methoxyl methyl singlet (3.79 S). A single vinyl proton quartet (5.4 S) 

CCXXIV H H CCXXIV -A MeO H CCXXIV-B MeO H 2,16-dihydro CCXXIV-C MeO Ac 2,16-dihydro 

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Contents L. Jaenicke and F.-J. Marner The Irones and Their Precursors. — M. Lounasmaa and P. Somersalo The Condylocarpine Group of Indole Alkaloids. — U. Sequin The Antibiotics of the Pluramycin Group (4//-Anthra [l,2- ]pyran Antibiotics). — R. M. Wenger Cyclosporine and Analogues — Isolation and Synthesis — Mechanism of Action and Structural Requirements for Pharmacological Activity. — H. Inouye and S. Uesato Biosynthesis of Iridoids and Secoiridoids. 

The evidence adduced thus far requires echitamidine to possess a pentacyclic ring system no double bonds are present, other than those present in the chromophore Ar—N—C—C—COOMe. Assuming a close connection with akuammicine, echitamidine may thus be formulated as LXVI, in which the proved presence of CH3—CHc/ determines the position of the hydroxyl group. Alternatively, assuming a structural resemblance to condylocarpine (LXVII), it may be formulated as LX VIII. 

The full absolute stereochemistry of condylocarpine was finally established by correlation with akuammicine (CCXXV) by way of its dihydro-derivative, tubotaiwine (CCXXIV, Section V, D Ref. 118a). The configurations of both condylocarpine and stemmadenine at position 15 are in fact natural, the positive rotation of the former being attributed to its inversion at C-7 with respect to the akuammicine group alkaloids. 

Membership to the condylocarpine rather than to the akuammicine group was established by mass spectral examination of the dihydro derivative (CCXXIV-B). The spectrum paralleled that of condylocarpine except in that the s peak appeared at m/e 257 (227 + 30 due to the aromatic methoxyl), while the indolic peaks were also shifted upward by 30 mass units. The UV-spectra of CCXXIV-B and its V-acetyl derivative, CCXXIV-C, corresponded to those of la,l,2,3,4,4a-hexahydro-7-methoxycarbazole and its iV-acetyl derivative, respectively (120a), thus placing the methoxyl group in the 11 position (condylocarpine numbering). The alkaloid CCXXIV-A may thus be formulated as 11-methoxy-14,19-dihydrocondylocarpine (48). 

Although the alkaloids of Aspidosperma populifolium are preponderantly of the aspidofractinine type, one of them (CCXXIV-A) was clearly excluded from this class by its IR- (ACHCl3 5.98 and 6.25 p, MeC C—C=C) and UV- (Table III) spectra. The latter was somewhat similar to that of condylocarpine (CCXV), the differences being accountable to an aromatic methoxyl group whose presence was indicated by the NMR-spectrum (OCH3, 3.74 S, coincident with the CC Me peak 3 aromatic protons only). A further difference from condylocarpine and akuammicine lay in the presence of an ethyl (0.70 S, triplet) rather than ethylidene side chain. 

Strychnine-Akuammicine-Condylocarpine-Uleine Group. Several variations of the strychnosplendine (62) theme isolated from Strychnos splendens have been examined in detail. A careful investigation has elucidated the complete pathway by which strychnine or its metho-salt can be degraded to the Wieland-Gumlich aldehyde or its metho-salt Sodium-ammonia cleavage of dihydro-strychnidine A methosulphate gives (63). 

Strychnine-Akuammicine-Condylocarpine-Uleine Group. Details39 have appeared of a synthesis1" of the ( )-dasycarpidones and ( )-epi-uleine. Ellipticine, appari-cine, and isoreserpiline have been isolated from Ochrosia silvatica 0a and the last two, together with 10-methoxy-19,20-dihydrocorynantheol, from O. vieillardii.40b... 

Strychnine-Akuammicine-Condylocarpine-Ellipticine Group. Full details have been given of structural work on hunteracine chloride and of Le Goffic s synthesis " of ellipticine reviewed" in Volume 4. It has been shown that the so-called strychnicine, isolated from leaves of Strychnos ignatii and S. nux-vomica many years ago, is probably vomicine. 11-Methoxydiaboline occurs... 

Strychnine-Akuammicine-Ellipticine Group. Akuammicine has been found in the seeds of Hunteria congolana and Na-methyl-2/3,16 -dihydroakuammicine in the leaves of Vinca minor. Tubotaiwine and condylocarpine occur in Aspid-osperma album tubotaiwine and apparicine have been isolated from Catharanthus ovalis, tubotaiwine also from Pandaca boiteau and Melodinus aeneus Baill., in the last of which tubotaiwine Nb-oxide also occurs. ... 

The principal members of this group (Chart 6.1) are derived mainly from the Wieland-Gumlich aldehyde (or its equivalent). An alternate ring closure gives the closely related aspidosperma-tine class of which condylocarpine is a member. None of the biosynthetic steps are known but might proceed according to the experimentally realized ftw-Mannich condensation (Chapter III, p. 25) equivalent to the hypothetical scheme in Chart 2.2 or by the routes sketched in Charts 2.3 or 12.2. 

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