Synthesis of the Vinblastine-like Antitumor Bis-Indole Alkaloid Navelbine Analogue Desethyldihydronavelbine

Article abstract of DOI:10.1021/jo00003a045

(R)-(-)-Ethyl nipecotate 6 was converted into the N-allyl bromide 10 whose derived Grignard reagent 11 was added to N-(phenylsulfonyl)-2-(methoxyoxalyl)indole 12 to give the diastereomeric alcohols 13.Removal of the indole protecting group from 13 and coupling with vindoline gave the separable diastereomers 15(S) and 17(R).Deprotection of 15/17 and treatment with formaldehyde/acetic acid gave desethyldihydronavelbine 5, and its 18'-epimer 19.Only the natural 18'-epimer exhibited any antitumor activity.