Total Synthesis of (+)-7-Deoxypancratistatin and (+)-7-Deoxy-trans-dihydronarciclasine

Abstract

The chiral and stereoselective synthesis of antimitotic phenanthridone alkaloids, (+)-7-deoxypancratistatin (1) and (+)-7-deoxytrans-dihydronarciclasine (2) is described.Both natural products were synthesized from the common compound (4), which had been prepared from D-glucose and employed for the synthesis of lycoricidine (3).The highly oxygenated phenanthridone alkaloids,l represented by pancratistatin?a7-deoxypancratistatin(1),2b 7-deoxy-trans-dihydronarciclasine (t)?c and lycoricidine (3)2d isolated from Amaryllidaceae plants are known to show wide range of biological activities such as antineoplastic,2c antivirus3 and plant growth regulatory activities.2bTheir interesting biological activity as well as challenging structures which embody four to six contiguous c h i d centers on the cyclohexane ring attracted much attention, and a number of synthetic study of these alkaloids have appeared to date.4.5 Very recently, asymmetric total syntheses of pancratistatin5b and 7-deoxypancratistatin5e.' have been reported.In this communication, we describe the chiral and stereoselective total synthesis of (+)-7-deoxypancratistatin (1) and (+)-7-deoxy-trans-dihydronarciclasine (2).Our synthetic tactic for the synthesis of 1 and 2 is based on the utilization of the common precursor (4), which had been effectively prepared from D- glucose and served as the key intermediate in our previous total synthesis of lycoricidine (3).5gHydrogenation of 4, which was prepared in an optically pure form from D-glucose% using Fenier's carbocyclization reaction6 and palladium catalyzed cyclization as the key steps, in the presence of Pd on