%0 Journal Article
%T Stereoselective Synthesis of (+)- -Conhydrine from R -(+)-Glyceraldehyde
%A Nageshwar Rao Penumati
%A Nagaiah Kommu
%J Organic Chemistry International
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/982716
%X Stereoselective synthesis of (+)-¦Á-Conhydrine was accomplished from protected (R)-(+)-glyceraldehyde, a familiar carbohydrate predecessor. Our synthetic strategy featured the following two key reactions. One is Zn-mediated stereoselective aza-Barbier reaction of imine 6 with allyl bromide to afford chiral homoallylic amine 7, and the other is ring-closing metathesis. 1. Introduction Exploiting natural products to ascertain a lead has always been important technique in drug discovery. Nature provides a rich source of bioactive compounds with significant biological activity and has therefore received considerable attention from the synthetic organic communities. The major class of biologically active molecules containing substituted piperidines has been widely present in the nature. The efforts to find a short and high yielding synthetic route for this class of natural products were always a contemporary interest. Some of the hydroxylated piperidine alkaloids are reported to be highly toxic and have drawn significant attention through their biological activity [1¨C3]. Conhydrine is one of the classes of alkaloids which were isolated by Wertheim from the poisonous plant, Conium maculatum L [4], in 1856. A highly fatal toxin causing paralysis of the skeletal musculature, 2-(1-hydroxyalkyl)-piperidine is a recurrent unit in many alkaloids such as Homopumiliotoxin 223 G 2, Slaframine 3, and Castanospermine 4 (Figure 1). Since the pioneering studies on the synthesis of (+)-¦Á-Conhydrine 1 by Galinovasky and Mulley [5], various methods have been reported normally based on auxiliary supported or chiral pool approach [6¨C18]. Figure 1: Some important piperidine, quinolizidine and indolizidine alkaloids. In view of the interesting biological and structural properties, especially the nitrogen containing alkaloids makes (+)-¦Á-Conhydrine 1 as an attractive and challenging synthetic target. As mentioned above (+)-¦Á-Conhydrine 1 was synthesized from various synthetic routes which involve a large number of steps to obtain the target molecule. Thus development of new methods for the synthesis of (+)-¦Á-Conhydrine 1 constitutes an area of current interest. Herein, an efficient synthesis of (+)-¦Á-Conhydrine 1 has been designed starting from 2,3-isopropylidene-R-(+)-Glyceraldehyde, by means of Zn-mediated stereoselective Barbier allylation as a key step, which was developed previously for the synthesis of different natural products in our laboratory [19¨C22]. To the best of our knowledge synthesis of (+)-¦Á-Conhydrine via aza-Barbier zinc allylation was not reported so far. 2.
%U http://www.hindawi.com/journals/oci/2014/982716/