Biosynthesis of ergot alkaloids. Evidence for two isomerizations in the isoprenoid moiety during the formation of tetracyclic ergolines

Journal of the American Chemical Society (Impact Factor: 12.11). 12/1968; 90(23):6500-7. DOI: 10.1021/ja01025a048
Source: PubMed


Canoclavine-I (1), but not chanoclavine-II (5) or isochanoclavine-I (6), is an efficient precursor of tetracyclic ergot alkaloids. Its cyclization to give agroclavine (2) is accompanied by a cis-trans isomerization at the double bond of the isoprenoid moiety. Experiments with mevalonic acids stereospecifically tritiated at C-4 indicate that another such cis-trans isomerization occurs earlier in the pathway. Thus the apparently "normal" labeling of tetracyclic ergot alkaloids from mevalonic-2-14C acid in the trans-carbon atom of the isoprenoid moiety is an accidental result caused by two isomerizations. The cyclization of chanoclavine-I proceeds with complete retention of the hydrogen at C-10, but with only 70% retention of the hydrogen at C-9. The latter result is discussed in view of possible mechanisms of the reaction.

3 Reads
  • Source
    • "This inversion occurs in a later step and it is of mechanistic importance as it is under full retention of hydrogen. Later, in agreement with these findings, DMAT (17) was detected as free intermediate in Claviceps mycelium when total synthesis of alkaloids was inhibited by depriving Claviceps cultures from supply with oxygen or adding ethionine that finally established a direct correlation between DMAT formation and alkaloid synthesis (Robber and Floss, 1968; Agurell and Lindgren, 1968). "

    Full-text · Chapter · Jan 1999
  • [Show abstract] [Hide abstract]
    ABSTRACT: Zusammen[assung: Sehr viele biochemische Reaktionen spielen sich an Kohlenstoffatomen ab, die zwei gleiche (a) und zwei verschiedene (bund d) Substituenten tragen, z.13. Methylen-Gruppen mit zwei verschiedenen Liganden (R-CH2-R'). Solche Caabd-Systeme bezeichnet man Ms prochirale Zentren. Die beiden Substituenten a sind nieht identisch, sondern unterscheiden sich in ihrer r~umlichen Anordnung relativ zu den anderen drei Gruppen. Enzymreaktionen an prochiralen Zentren sind im allgemeinen stereospezifisch, d.h. ein gegebenes Enzym reagiert bei einer Substitutions- oder ]Eliminierungsreaktion nur mit einem der beiden rgumlich verschiedenen Substitueuten a. Durch stereospezifische Isotopenmarkierung eines yon beiden lassen sich die zwei Substituenten a unterscheiden, und man kann somit den stereoehemischen Verlauf enzymatischer Reaktionen an prochiralen Zentren bestimmen. In dem folgenden Artikel wird die Anweudung dieser Methodik zur Nl~rung verschiedener biochemischer Probleme diskutiert und an Beispielen illustriert.
    No preview · Article · Aug 1970 · The Science of Nature
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Rǒle of Paliclavine in the Biosynthesis of Ergot AlkaloidsFeeding of [N-14CH3]-paliclavine to submersed cultures of Claviceps paspali Stevens et Hall and to surface cultures of the ergot fungus from Pennisetum typhoideum Rich. has shown that paliclavine is not involved in the biosynthesis of either the ergolene carboxylic acids or the tri- and tetra-cyclic clavines.
    No preview · Article · Nov 1975 · Helvetica Chimica Acta
Show more