Convenient Synthesis of Cyclohexa[a]pyrrolo[2,1-b][3]benzazepine, a Cephalotaxus Alkaloid Analogue

Irradiation of N-(3-hydroxy-4-methoxyphenethyl)-3-(2-iodo-5methoxyphenyl)propionamide (11) in methanol in the presence of sodium hydroxide furnished 3-hydroxy-2,12-dimethoxy-6,7,9.1C-tetrahydrodiknz-[d,flazecin-8(5H)-one(14) which was successfully led to cephalotaxine analogue (17) bearing py&olo[2,1-b][3]benzazepine skeleton by reduction with borane followed by Birch reduction and subsequent acidic treatment.The structure of 17 was established by means of X-Ray crystallography.We previously reponed that bromophenolic amides underwent photochemical cyclization reaction to form easily diknz[d,flazecine skeleton,'.' which was subjected to reduction with horane followed by Birch reduction and subsequent acidic treatment to give homoerythrinan derivative?The dibenz[d,flazecine base (4) might be the important intermediate in the biosynthesis of homoerythrinan alkaloids and cephalotaxan alkaloids' (Scheme 1) whose estef derivatives, harringtonine (2) and homohamingtonine (3), have potent antileukemic activity.'From view of spectrum of the biological activity and unique structural features, there are many reports on the synthesis of cephalotaxine (1)' and its analogues, homocephalotaxine6 and aza-cephalotaxine derivative,' whose pivotal skeleton is pyrrolo[2,1b][3]henzazepine.In this paper, we wish to describe a novel route for the synthesis of a cephalotaxine analogue (17) having the pyrrolo[2,1-bl[3]benzazepine skeleton from a dibenz[d,flazecine base (15) using Birch reduction followed by acidic treatment.First, the dibenz[d,flazecine base (15) was prepared as shown in Scheme 2. The condensation reaction of P-(2-iodo-5-methoxyphenyl)propionic acid (8)' and 3-benzyloxy-4-methoxyphenethylamine (9) in refluxing xylene gave 10 in 73% yield.