Les β‐cétonitriles groupes protecteurs de la fonction amine. Préparation d'amino‐alcools

Abstract

/l-Ketonitrile-Derived Protecting Groups of the Amino Function. Synthesis of Amino AlcoholsThe amino group of natural L-amino acid esters is protected by condensation with 2-oxocyclopentanenitrile (1) or 2-formyl-2-pheny~dtetonitrik (10). Only the ester group of the formed cyanoenamino esters 2 and 11 reacts with nucleophilic reagent!; such as organometallics (RMgX, RLi), borohydrides, or metal amides, whereas the cyanoenamino group is unchanged (Schemes I and 2). Cyanoenamino alcohols obtained by reduction of cyanoenamino esters 2 are hydrolyzed under acidic conditions to amino alcohols with retention of the configuration of the starting amino acid. This sequence of reactions allows to prepare derivatives of L-tyrosinol from (-)-L-tyrosine (see, e.g., Scheme 4 ) . Cyanoenamino esters 11 are readily methylated at the N-atom to give N-methylated cyanoenamino esters (Scheme 3 ) . This property is exploited on the way of a multistep procedure to obtain N-methylated amino alcohols homologous to natural (-)-(1 R,2S)-ephedrine.Introduction. -Nous avons deji d6crit [l] [2] la preparation des amino-alcools 4 a partir d'esters d'amino-acides naturels, dont la fonction amino est masquke sous forme cyanohamino dtrivt du 2-oxocyclopentanenitrile (1; schirna 1 ). La fonction ester des cyanotnamino-esters 2 (Z = OR3) peut subir diverses attaques nucltophiles qui ne modifient pas la configuration d'origine. Si le reactif nucleophile 'Nu' mis en jeu est un organomktallique (KMgX ou RLi), on obtient des cyanoenamino-alcools optiquement actifs 3 (R' = R2 = alkyle ou aryle), le groupe cyanotnamino restant inchangt [l]. Si 'Nu' est un amidure, l'esttx est transformi: en amide disubstitut 5 (Z = N R R ) avec conservation de l'activitk optique; il est ensuite possible d'acceder, par action du phenyllithium (PhLi), aux cetones ,aromatiques correspondantes 6 (Z = Ph), puis par action du NaBH, dans I'EtOH, aux alcools secondaires 3 (R' = H, R2 = Ph) [2]. L'tlimination du groupe protecteur 2-cyanocyclopent-1 -enyle (Ccp) effectuke par hydrolyse acide conduit finalement aux amino-alcools 4 et au reactif 1 (schPrna I ) . Ces rtactions s'effectuent sans racemisation [3].

Stereochemical Analysis of the Enzymic Reduction of the Double Bond of α‐ and β‐Substituted Nitrostyrenes and α‐Ethoxycinnamaldehyde through Deuterium Labelling Experiments

“…Compound 5 was assigned ( R ) absolute configuration because it was converted by Zn/H 2 SO 4 /EtOH reduction20 into ( R )‐ 7 (Scheme ), whose absolute configuration was known 21. In a separate experiment, product 2 was submitted to catalytic hydrogenation with deuterium gas (AcOEt, moist 5 % Pd/C) to provide the [2,3‐ 2 H 2 ] derivative 8 .…”

“…for ( S )‐7 [ α ] D 20 = +48.8 ( c = 2, aq. HCl)] 21. In the deuterated series from yeast, the free amine 7 for the 2 H NMR studies was obtained as follows.…”

Total Synthesis of FR901483

“…Commercial l -tyrosine was converted to building blocks 2 and 3 6 (Scheme 1). The union of 2 and 3 to furnish oxazoline 4 was achieved in a single step, and without erosion of stereochemical integrity, by the Vorbrüggen method .…”