Chanoclavine I aldehyde

In an effort to avoid the confusion brought about by two allylic cis-trans isomerizations as described above, [14C,17-3H]chanoclavine-I-aldehyde (55) was prepared as described earlier (39). But again it was incorporated into elymoclavine (54) with retention of 3H, now found at C-7 (74). 

Ergot.—When [17- H, C]chanoclavine-I (110) was administered to Claviceps, the elymoclavine (112) isolated showed a 53% tritium retention, indicating that in the conversion of (110) to (112) one of the methylene hydrogens at C-17 is lost. This suggested the possible intermediacy of chanoclavine-I-aldehyde (111) in this sequence, and indeed (111) with a C-17 tritium label was significantly better incorporated into elymoclavine than was chanoclavine-I the tritium... 

The need for ATP for the reaction in the cell-free system allowed ring-closure at some point in this sequence by nucleophilic displacement of phosphate. This mode of ring-closure, however, does not accommodate loss of a C-17 proton [and the intermediacy of chanoclavine-I-aldehyde (111)]. ... 

Formation of the ergolene D-ring (Scheme 3) requires first the oxidation of 16 to chanoclavine-I-aldehyde (17), dehydration to the C(7)-N(6) iminium ion (18), and reduction of the iminium ion to form agroclavine (19) 10). During this process, the hydroxymethyl group, which is cis to the C(9)-hydrogen atom in 16, ends up trans to the C(9)-hydrogen in 19. Thus, a second epimerization occurs before or... 

Matuschek M, Wallwey C, Wollinsky B, Xie X, Li S-M (2012) In vitro conversion of chanoclavine-I aldehyde to the stereoisomers festuclavine and pyroelavine controlled by the second reductitm step. RSC Adv 2 3662-3669... 

Wallwey C, Matuschek M, Li S-M (2010) Ergot alkaloid biosynthesis in Aspergillus fumigatus conversion of chanoclavine-I to chanoclavine-I aldehyde catalyzed by a short-chain alcohol dehydrogenase FgaDH. Arch Microbiol 192 127-134... 

Xie X, Wallwey C, Matuschek M, Steinbach K, Li S-M (2011) Eormyl migration product of chanoclavine-I aldehyde in the presence of the old yellow enzyme FgaOx3 from Aspergillus fumigatus. a NMR structure elucidation. Magn Reson Chem 49 678-681... 

Figure 15 Closure of ring D chanoclavine-I cyclization. and indicate loss of tritium diring the conversion of chanoclavine-I to chanoclavine-I-aldehyde...

Naidoo, B., Cassady, J.M., Blair, G.E. and Floss, H.G. (1970) Biosynthesis of ergot alkaloids. Synthesis of chanoclavine-I-aldehyde and its incorporation into elymoclavine by Claviceps. J. Chem. Soc. Chem. Comm., 471—472. 

Maier, W., Erge, D., Schmidt, J. and Groger, D. (1980b) A blocked mutant of Claviceps purpurea accumulating chanoclavine-I-aldehyde. Experientia, 36, 1353-1354. 

Besides agroclavine and elymoclavine, also other clavine alkaloids can be used for the preparation of certain semisynthetic derivatives. Although no derivatives prepared by modification of the clavine molecule are used in therapy, some preparation procedures yielding such clavine alkaloids are protected by patents. Among 6, 7-secoergolenes, i.e., alkaloids with an open ring D of the ergoline structure, chanoclavine-I and chanoclavine-I aldehyde have been patented. 

H,4- " C]Chanoclavine was fed to Claviceps strain SD 58. The elymoclavine isolated from this culture showed a tritium retention of 53%, demonstrating the loss of one of the labeled hydrogens from C(17) of chanoclavine I (Floss et al., 1974a). The results suggested that chanoclavine I aldehyde is formed as an intermediate in D-ring closure. [17- H,4- " C]-Chanoclavine I aldehyde was prepared from chanoclavine I and tested for... 

These results support a mode of ring closure shown in Fig. 5. So far, it has not been possible to synthesize the proposed intermediate isochanoclavine I aldehyde. Chanoclavine I aldehyde is converted to chanoclavine I in cultures of Claviceps, but the conversion of chanoclavine I to chanoclavine I aldehyde could not be demonstrated because chanoclavine I aldehyde could not be recovered from the cultures (Floss et aL, 1974a). Nevertheless, the evidence strongly suggests that chanoclavine I aldehyde is an intermediate between chanoclavine I and the clavine alkaloids. 

A mechanism incorporating the formation of chanoclavine I aldehyde and the intermolecular transfer of the hydrogen at C(9) is shown in Fig. 7. The carbinolamine is the product in path a, and isochanoclavine I aldehyde... 

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