Karlheinz Drauz

O-Acetyl-L-homoserine: A versatile synthon for the synthesis of L-homoserine peptides and 3-amino-2-pyrrolidinones

Although L-homoserine is a naturally occurring amino acid with important biological properties, only few examples of homoseryl peptides are known, which have been mainly prepared by using either the benzyl [1,2] or the trityl [3,4] group for the O-protection. Furthermore, homoserine amides are potential precursors for the introduction of a ring, which can act as conformational constraints in peptides and peptidomimetics [5-7]. Herein, we report new methods for the preparation of homoserine amides and their conversion into

A novel synthetic route to L-proline (Amino acids ; 7)

Reaction of L-5-oxoproline esters L-2 with phosgene at 0° C gives L-5,51-dichloro-1-(chlorocarbonyl)proliene esters L-6 ,which readily lose hydrogen chloride to form L-5-chloro-1-(chloroarbonyl)-4,5-dehydroproline esters L-7. Catalytic hydrogenation (Pd/C, 180 bar) of L-7 yields L-1-(chlorocarbonyl)proline esters L-15 and thence, upon hydrolysis, L-proline ( L17 ). A one-pot reaction for the whole sequence is described, starting from easily accessible L-5-oxoproline esters and yielding L-proline in 78% overall yield and 99.7% optical purity.

Darstellung von Aminosäuren aus Halogencarbonsäure-alkylestern mit Alkalimetallcyanaten (Aminosäuren ; 1)

α- und ω-Halogen- sowie α,ω-Dihalogencarbonsaure-alkylester reagieren mit Kaliumcyanat in Gegenwart von Alkoholen in dipolaren aprotischen Losungsmitteln bei 80-120°C in guten Ausbeuten zu α- und ω-(Alkoxycarbonylamino)- bzw. α,ω-Bis(alkoxycarbonylamino)carbonsaurealkylestern (Mono- bzw. Diuerthane). Die hydrolytische Spaltung dieser Verbindungen mit einem wasrigen Salzsaure/Ameisensaure-Gemisch fuhrt in meist quantitativen Ausbeuten zu den entsprechenden Aminosaure-hydrochloriden. n nα- and ω-halo- as well as α,ω-dihalocarboxylic alkyl react with potassium cyanate in the presence of alcohol at 80-120°C in dipolar aprotic solvents to yield α - and ω-(alkoxycarbonyl-amino)- and α,ω-bis(alkoxycarbonylamino)carboxylic alkyl esters, respectively, in good yields. Hydrolytic cleavage of these mono- or diurethanes with an aqueous solution of hydrochloric acid/formic acid leads to the corresponding amino acid hydrochlorides in nearly quantitative yields.