Paper
Synthesis of Azaspiro[4.4]nonanes as Key Structures of Several Bioactive Natural Products
Published 2005 · Serry A. A. El Bialy, Holger Braun, Lutz F. Tietze
ChemInform
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Abstract
The 1-azaspiro[4.4]nonane ring system (1) is a unique structure and represents the core skeleton of cephalotaxine (2), whose a-alkylmalate monomethyl esters, e.g. homoharringtonine, show a pronounced antileukemic activity.1 After treatment with homoharringtonine, a high rate of complete haematological remission was observed in patients with chronic myelogenous leukemia resistant to all existing chemotherapies, including interferon a.2 In addition, the 1-azaspiro[4,4]nonanones 3 have been used as templates for constructing synthetic receptors and as intermediates in the synthesis of enzyme inhibitors (Figure 1).3 Consequently, considerable attention has been directed towards the development of new methods for the construction of the 1-azaspiro[4,4]nonane ring system 1. The synthetic strategies can be divided into two groups: formation of a cyclopentane ring onto a pre-existing pyrrolidine derivative, and formation of a pyrrolidine ring onto a pre-existing cyclopentane derivative.
The 1-azaspiro[4.4]nonane ring system is crucial for the synthesis of bioactive natural products, such as cephalotaxine, and has potential therapeutic applications in treating chronic myelogenous leukemia and enzyme inhibitors.
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