Eine neue Synthese von Vinblastin-Derivaten. III: Synthese und Reaktionen von 21, Nb-seco-Cleavamin-Derivaten als Vorläufer zu 20'-Deethyl-20'-deoxyvinblastin und (±)-16α-Methoxycarbonyl-20-deethyl-15,20-dihydrocleavamin

Zusammenfassung In a new concept for the synthesis of 20'-deethyl-20'-deoxyvin-blastine, N b - seco -cleavamine derivatives 1a , 2a are possible precursors. For the synthesis of these compounds the indolizino(5,4-b]indoles 8I , II were treated with benzyl chlorofomate/aq. sodium cyanide to give by C/D ring cleavage the nitrile 9 as a single diastereomer. Starting with 9 , the methyl esters 14 and 27 and the lactams 22 , 23 and 24 are obtained as pure diastereomers. The relative stereochemistry of lactams 22 , 23 , 24 and of carboxylic acid precursors is deduced from the outcome of the closure of ring D in seco -cleavamine 27 forming 16-methoxycarbonyl-20-deethyl-15,20-dihydrocleavamine 28 with epivincadine configuration. Despite the “wrong” stereochemistry of lactams 22 , 23 and 24 , chloroindolenine derivatives 29a and 29c were synthesized. The coupling reactions of these compounds with N,N-dimethyl-m-anisidine as a model for vindoline were unsuccessful.