Synthesis of DEFG ring system of cneorins
Ari M. P. Koskinen* and Ainoliisa J. Pihko
Laboratory of Organic Chemistry, Department of Chemistry, Helsinki University of Technology, PO Box 6100, FI-02015 TKK, Finland
E-mail: ari.koskinen@tkk.fi
Abstract
The cneorins have been isolated from the xerophytic shrub Cneorum pulverulentum, which is native to the Canary Islands. They are natural products containing a [4.3.1]propellane ring system (DEFG rings) as the northern part of the molecule and a 5,5-spiroketal unit and a butenolide moiety (A ring) as the southern part. The synthesis of the DEFG ring system of the cneorins is described. The key steps include: intramolecular cyclopropanation of a diazomalonate providing the EFG ring fragment and an anionic cyclization of a sulfone yielding the [4.3.1]propellane ring system.
Keywords: Total synthesis, natural products, cneorins, intramolecular cyclopropanation of diazomalonates
Introduction
The cneorins (1, 2) (Figure 1) were originally isolated from the xerophytic shrub Cneorum pulverulentum, native to the Canary Islands, in the late 1970’s.1 This shrub hosts a variety of bitter principles, all of which contain the [4.3.1]propellane ring system.2 These oxidized pentanortriterpenes (C25 compounds) also have other interesting structural features in common, such as a 5,5-spiroketal unit and a butenolide moiety. The relative stereochemistry of the parent natural products were initially reported based on degradation studies, and later confirmed by X- ray diffraction structures. The absolute stereochemistry has been indirectly determined for only one derivative of cneorin C, and must be considered with caution for the other structural members of these natural products. Biogenetically these compounds are thought to be related to the limonoid triterpenes.3 Due to lack of material from natural sources, these compounds have not received proper pharmacological screening. In addition to Cneorum pulverulentum, the Cneoraceae plant family consists of two other species, Cneorum tricoccon, which is native to coastal areas of the western Mediterranean, and Cneorum trimerum, which belongs to the flora of
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