Application of the beta-azidonation reaction to the Synthesis of the antitumor alkaloid (+)-pancratistatin

o-vanillin 21 was converted into 24 following literature procedures. Treatm ent of 24 with n-BuLi/THF followed by addition of 25 gave 26. Dehydration ( POCl3/pyridine/DBU), hydrogenation and hydrolysis of 26 gave the ketone 29. Chirality was introduced by deprotonation of 29 with the lithium salt of ( +)-bis(alpha-methylbenzyl)amine, followed by triisopropylsilyl trifluoromet hanesulfonate to give 30 (95%). beta-Azidonation of 30 with (PhIO)(n)/TMSN3 rapidly produced 31 (95%) as a mixture of trans- and cis- diastereomers in a 3.5:1 ratio. Reduction with LiAlH4 followed by methyl chloroformate/pyri dine gave 32, which on treatment with MCPBA/CH2Cl2/imidazole resulted in 33 . Hydrolysis of 33 gave 34, which when exposed to KOBut/HMPA at 90 degrees C resulted in 39. After conversion of 39 into enone 42, epoxidation with Na HCO3/H2O2/MeOH gave 43. Reduction of 43 with L-selectride followed by solvo lysis with sodium benzoate in water gave 46, which was immediately acetylat ed to give 47. Lactam formation (Tf2O/DMAP) converted 47 into 48 and the re gioisomer 49 (7:1). The mixture of 48 and 49 demethylated to give 50 and th e acetate protecting groups removed to give (+)pancratistatin 1. (C) 1998 E lsevier Science Ltd. All rights reserved.