Synthese von zwei diastereomeren natürlichen Dihydroxyprolinen: 2,3‐trans‐3,4‐trans‐3,4‐Dihydroxy‐L‐prolin und 2,3‐cis‐3,4‐trans‐3,4‐Dihydroxy‐L‐prolin

Ausgehend von 2-Pyrrolcarbonsaure wird uber 3,4-Dehydro-D,L-prolin (5) das N-Boc-Derivat 6 durch Kristallisation mit R( + )-1-(4-Nitrophenyl)ethanamin in die Antipoden gespalten. Der daraus zugangliche N-Tosyl-3,4-dehydro-L-prolin-methylester (L-7) ergibt mit Trifluorperessigsaure die 3,4-Epoxyester 8a und 8b, die bei der Hydrolyse eine Mischung aus dem N-Tosyl-3,4-dihydroxy-L-prolinester (9a) und der Saure 10b ergeben. Die Saure 10b wird durch Extraktion mit Hydrogencarbonatlosung vom diastereomeren Ester 9a getrennt. Die Trennung gelingt auch durch Reaktion mit Chlorameisensaure-isobutylester, wobei 9b unverandert bleibt und 10b ein γ-Lacton bildet. Nach Offnung des Lactonrings resultieren mit Natrium in flussigem Ammoniak die Dihydroxy-L-proline 3 (aus 9b) und 4 (aus 10b), die mit naturlichem Material in allen Eigen-schaften ubereinstimmen. Synthesis of Two Naturally Occuring Diastercomeric Dihydroxyprolines: 2,3-trans-3,4-trans-3,4-Dihydroxy-L-proline and 2,3-cis-3,4-trans-3,4-Dihydroxy-L-proline Starting from 2-pyrrolecarboxylic acid the N-Boc derivative 6 is resolved into its optically active constituents by crystalisation with R(+)-1-(4-nitrophenyl)ethaneamin. The N-tosyl-3,4-dehydro-L-proline methyl ester (L-7) derived from this is converted by means of trifluoroacetic acid to the 3,4-epoxy esters 8a and 8b, the hydrolysis of which yields a mixture of the N-tosyl-3,4-dihydroxy-L-proline (9a) and the acid 10b. The acid 10b can be separated from the diastereomeric ester 9a by extraction with hydrogen carbonate solution. The separation can also be achieved by reaction with isobutyl chloroformate by which 9b keeps unchanged and 10b forms a γ-lactone. After opening the lactone ring and treatment with sodium in liquid ammonia the dihydroxy-L-prolines 3 (from 9b) and 4 (from 10b) are obtained the properties of which are completely in accord with those of naturally occuring material.

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