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.

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    • "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). "
    Ergot - The Genus Claviceps, Edited by V. Kren, L. Cvak, 01/1999: pages 95 - 163; Harwood Academic Publishers London.
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    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.
    Helvetica Chimica Acta 11/1975; 58(8):2492 - 2500. DOI:10.1002/hlca.19750580829 · 1.14 Impact Factor
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    ABSTRACT: Es wird eine Vorschrift mitgeteilt, die sich dafür eignet mit guter Ausbeute das spezifisch in einer Methylgruppe 14C- oder 13C-markierte 4-(3-Methyl-2-butenyl)tryptophan (6) zu synthetisieren. Weiter wird beschrieben, wie man die E- und Z-isomeren Nitrile 11E bzw. l l Z und daraus die ihnen entsprechenden Aldehyde 12E bzw. 1 2 2 sowie die Alkohole 8E bzw. 8Z darstellt. Durch „Umkehrung” der Wittigreaktion unter Verwendung des Phosphoniumsalzes 15 und Brenztraubensäureester kommt man zu den Estern 4Ea und 4Za und von diesen zu den entsprechenden Alkoholen. Ebenfalls aus 15 und 1,3-Diacetoxyaceton erhält man die Dihydroxyverbindung 18. - Ein besonderer Vorteil bei diesen Synthesen ist die Verwendung der Tosylgruppe am Indolstickstoff. - Einige Zwischenprodukte können mit guten Ausbeuten nur unter Hochdruck gewonnen werden.Biosynthesis of Ergot Alkaloids, V1). - New Synthetic Approaches for Possible Intermediates in Ergot Alkaloid Biosynthesis A procedure is given for the facile synthesis of 4-(3-methyl-2-butenyl)tryptophan (6), which can be specifically labelled with 14C or 13C in one of the methyl groups. Furthermore, the preparation of the isomeric nitriles 11E and l l Z is described, and a method given for their transformation into the corresponding aldehydes 12E and 1 2 2 and alcohols 8 E and 8 2 . „Inverted” Wittig reaction using the phosphonium salt 15 and ethyl pyruvate affords the isomeric esters 4Ea and 4Za, which furnish the alcohols 8E and 8 Z on reduction. Reaction of 1,3-diacetoxyacetone with 15 leads to the dihydroxy compound 18. - A special advantage of these syntheses is the use of the tosyl group at the nitrogen of the indole nucleus. - Some of the intermediates could be obtained in good yields only under high pressure.
    European Journal of Organic Chemistry 09/1976; 1976(7-8):1475-1486. DOI:10.1002/jlac.197619760737 · 3.07 Impact Factor
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