Chanoclavine 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). 

An intramolecular cycloaddition reaction is also a vital feature of Oppolzer s synthesis (Scheme 5).336 Here the cycloaddition reaction occurs on an unsaturated nitrone ester (39) (not isolated). Again, the aldehyde derived from oxidation of the diol (40) gave entirely the ( )-olefin on reaction with crystalline a-methoxy-carbonylethylidenetriphenylphosphorane, which allowed the synthesis of (+)-chanoclavine I (34) to be completed in an overall yield of 14% from indole-4-aldehyde. In contrast, the Horner-Emmons reaction on the aldehyde from... 

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)]. ... 

Ergot Alkaloids.—The hemiterpenoid unit of the ergot alkaloids is interesting in that, as expected, only one carbon atom is labelled by [2- C]mevalonic acid [marked by in formulae (14)—(17)] but the stereochemistry of this atom changes. Extensive studies by Floss etalf indicate that chanoclavine I (14) is converted into elymoclavine (17) via the aldehyde (15) and possibly via agroclavine (16) (however, see ref. 36a). This process involves two isomerisations about the isolated double bond. In dimethyl allyl pyrophosphate (5) the trans-methyl is labelled by... 

Ergot Alkaloids. — There is good evidence that ergot alkaloids, represented by elymoclavine (76), are biosynthesized by way of chanoclavine-I (74) and the aldehyde (75) (cf. ref. 2 Vol. 5, p.27). It has now been shown, with cultures of a Claviceps strain and using samples of chanoclavine-I (74) chirally tritiated at C-17, that bioconversion of (74) into (76) involves... 

In the conversion of chanoclavine-I (119) into elymoclavine (123) one of the C-17 hydrogens is lost. (The other appears at C-7 of elymoclavine as expec-ted.) This suggested that the aldehyde (124) might be an intermediate. This was strongly supported by the efficient incorporation of (124) into elymoclavine tritium label from C-17 in the precursor appeared at C-7 of the product OH... 

The properties of an enzyme system isolated from ergot which catalyses the transformation of chanoclavine-I (119) to agroclavine (122) have been investigated. The enzyme system was found to convert chanoclavine-I and chano-clavine-I-aldehyde (124), but not isochanoclavine-I (120) into agroclavine (122). Further evidence is thus provided for the normal elaboration of ergot alkaloids as being chanoclavine-I (119)— the aldehyde (124)— agroclavine (122). 

The seeds of Ipomoea violacea, variety Pearly gates , were earlier reported to contain an ergoline acid of unknown constitution, which proves to be chano-clavine-I acid (56), since reduction (LiAlH4) gives rise to chanoclavine-I (57) conversely, oxidation of chanoclavine-I by means of manganese dioxide gives the related aldehyde, which, on further oxidation by manganese dioxide in methanol in the presence of cyanide ion, affords chanoclavine-I acid methyl ester directly. " ... 

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... 

The chanoclavine cyclase activity is dependent on NADH or NADPH, Mg, and ATP (10). The scheme we propose here is consistent with an NAD(P)H requirement for the third enzyme (reductase). Also, we expect the oxidized form, NADP or NAD, to oxidize 16 to aldehyde 17. Furthermore, and as stated above, it is possible that NAD(P)H is involved in the oxidation and reduction reactions to generate iminium ion 21. However, it is not obvious why there is a requirement for ATP. Clearly, elucidation of the mechanisms underlying the steps in D-ring formation will continue to reveal some interesting biochemistry. 

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. 

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