New avenues in nitrenium ions and carbene chemistry: Synthesis of azaspirane and ulosonic acid natural products.

摘要

Part 1. A novel method for the stereospecific preparation of [4.5]spiroketal glycosides utilizing the [1,5]-C-H bond insertion of alkylidenecarbenes has been developed. In contrast to existing methods for the synthesis of spiroketals, this approach does not rely upon thermodynamic or kinetic control to set the configuration of the acetal stereocenter but rather capitalizes on the fact that alkylidenecarbene insertion proceeds with retention of configuration. The development of this chemistry and its application to the synthesis of the ulosonic acid natural products DAH, KDO and KO will be presented.; Part 2. The synthesis of (±)-desmethylamino FR901483, an analog of the potent immunosuppressant (−)-FR901483, has been accomplished. The central theme of this venture was the use of an N-methoxy- N-acylnitrenium ion-induced spirocyclization to prepare the 1-azaspiro[4.5]decane ring system of this target molecule. A novel strategy for the stereocontrolled preparation of 1-azaspiranes, based on the π-facial selective spirocyclization of N-acylnitrenium ions has also been developed. The application of this approach to the formal synthesis (−)-perhydrohistrionicotoxin and the preparation of a key building block for the synthesis the marine cytotoxin fasicularin will be described.