Sir Derek Barton zum 70. Geburtstag gewidmet (24. VIII. 88)
Synthesis of the Lichen Macrolide (+)-Aspicilin Using Photolactonization as a Key Reaction(+)-Aspicilin, obtained from a lichen source of the Black Forest, has been proven to have the absolute configuration depicted by formula la. It is easily built up from phenol (14a), 1,9-nonanediol (13a), and (-)-(S)-methyloxirane (6) (cJ Scheme 2 ) . The latter building block provides the first stereogenic center C(17). The heterocycle is produced by photolactonization, fairly early during the course of the synthesis. The second stereogenic center is generated diastereoselectively at C(6) in compound 8, conveniently available from photolactone 9a or 9b/9c. Its absolute configuration depends on the kind of reducing agent and is controlled by long-range conformational transmission of chiral information. To explore the cause of stereoselection, 2D-NMR spectroscopy, X-ray structural analysis, and/or computer-aided conformational search followed by energy minimization have been used extensively, revealing the importance of the local conformation of the lactone moiety. Compound 8, on treatment with Yamamoto's reagent, affords pre-target compound 7a almost exclusively. The latter compound, on pyridine-accelerated dihydroxylation with OsO,, gives preferentially (+)-Aspicilin.
Photolactonization: a Novel Synthetic Entry to Macrolides 0-Quinol acetates, hydroxyalkylated at C(6), are easily accessible from simple phenols by Wessely acetoxylation (preferentially catalyzed by BF,). On UV irradiation (in the presence of an appropriate tertiary amine), they are smoothly converted to macrocyclic lactones. Subtle conditions have been elaborated to lead to high overall yields, and the scope of the conversion of phenols to macrolides has been elucidated 1. Einleitung. -Der Begriff 'Photolactonisierung' kennzeichnet ein photochemisches Verfahren zur Herstellung von Makromonoliden C und/oder Makrodioliden D (s.
Bei Verwendung von Isopropylisocyanat und methanolischer HCI bilden sich unter den angegebenen Bedingungen neben Isopropylcarbamoyl-aminosaure-methylestern auch N-Isopropylhydantoine, die zwar ebenfalls gaschromatographisch getrennt werden konnen, jedoch nicht vo1-lig konfigurationsstabil sind. In einigen Fallen erwies es sich als vorteilhaft, das Peptid vor der Umsetzung rnit Isocyanat rnit HCI/Isopropylalkohol (1.0 N) zu verestern, denn die Loslichkeit in Pyridin und der Umsatz zum Carbamoylderivat werden dadurch haufig verbessert.Ein vollstandiger Abbau von Peptiden in der Grii13en-ordnung von 8-10 Aminosiiuren gelang rnit 0.5-1 mg Ausgangsmaterial.Die Methode wurde unter anderem bei der Untersuchung eines synthetischen Octapeptids der Sequenz H-Val- Der Vergleich der nach Totalhydrolyse und der nach sequentiellem Abbau bestimmten Racemisierungsanteile (Tabelle 1) 1aBt erkennen, da13 auch die Hydrolyse des Peptids in 6 N HCI zur Racemisierung beitragt.
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