Synthesis of the Diastereomers of Dethiobiotin Using the Conjugate Addition of 4-Phenyloxazolidin-2-one to a Nitroalkene - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue European Journal of Organic Chemistry Année : 2000

Synthesis of the Diastereomers of Dethiobiotin Using the Conjugate Addition of 4-Phenyloxazolidin-2-one to a Nitroalkene

Résumé

Natural D-dethiobiotin and its three stereoisomers were prepared from a single nitroalkene 2. Conjugate addition of the potassium salt of (R)-4-phenyloxazolidin-2-one 3 to 2 led to two diastereomeric nitro compounds 6 and 7. Their enantiomers were prepared from (S)-3. These compounds were converted in three analogous steps into the dethiobiotin isomers as their methyl esters. In the course of a study into the biosynthesis of biotin, a vitamin which acts as a cofactor for carboxylase reactions, we were interested in the synthesis of the various diastereomers of the biotin precursor dethiobiotin 1. This cis-substituted imidazolidin-2-one, derived from the corresponding diamine, is converted into biotin under the action of the enzyme biotin synthase (Scheme 1). [1-3] Scheme 1. Biosynthesis of biotin In this article, we describe the synthesis of all four diastereomers of dethiobiotin. The retrosynthetic analysis for the dethiobiotin isomers is presented in Scheme 2. The two nitrogen-containing functional groups could be introduced using the conjugate addition of a nitrogen nucleophile to nitroalkene 2 of the appropriate chain length and the carboxylic function. We have previously reported the highly stereoselective conjugate addition of the potassium salt of 4-phenyloxazolidin-2-one 3 to monosubstituted nitroalkenes and the conversion of a corresponding adduct into an enantiomerically pure monosubstituted imidazolidin-2-one. [4,5] When applied to disubstituted nitroalkenes, pairs of diastereomers should be obtained. Furthermore, since both enantiomers of 3 are commercially available, the method would allow for the synthesis of the four isomers of dethiobiotin. Scheme 2. Retrosynthetic analysis of dethiobiotin diastereomers Nitroalkene 2 was prepared according to the sequence described in Scheme 3. Commercially available 7-bromoheptanenitrile was converted in three efficient steps into the known methyl 7-nitroheptanoate 4. [6] Nitroaldolisation of 4 with acetaldehyde afforded nitro alcohol 5. Acetylation of 5 followed by treatment with basic alumina yielded nitro-alkene 2 as a 90:10 mixture of (E)-and (Z)-isomers.

Domaines

Chimie organique
Fichier principal
Vignette du fichier
Eur JOC Nitroalkene.pdf (456.66 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-02503542 , version 1 (10-03-2020)

Identifiants

Citer

Denis Lucet, Philippe Heyse, Arnaud Gissot, Thierry Le Gall, Charles Mioskowski. Synthesis of the Diastereomers of Dethiobiotin Using the Conjugate Addition of 4-Phenyloxazolidin-2-one to a Nitroalkene. European Journal of Organic Chemistry, 2000, 2000 (21), pp.3575-3579. ⟨10.1002/1099-0690(200011)2000:21<3575::AID-EJOC3575>3.0.CO;2-R⟩. ⟨hal-02503542⟩
36 Consultations
102 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More