A model synthetic approach towards the furanacetal component of azadirachtin: a potent insect antifeedant
Sushil Raina, B. A. Bhanu Prasad, and Vinod K. Singh*
Department of Chemistry, Indian Institute of Technology, Kanpur, India - 208 016
E-mail:
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Dedicated with respect to Professor Sukh Dev on his 80th birthday
(received 30 Sep 02; accepted 16 Dec 02; published on the web 03 Jan 03)
Abstract
In this article, a model synthetic approach towards the furanacetal component of azadirachtin has been described from a-D-glucose. Tandem radical cyclization was the key step for the formation of the desired tricyclic system. The reaction provided a bicyclic system instead of the desired tricyclic molecule. The reason for the unsuccessful tandem cyclization was proposed to be mainly energy factors.
Keywords: a-D-glucose, azadirachtin, tandem radical cyclization
Introduction
The fused cyclic acetal moiety is embodied in a large number of natural products many of which display interesting biological properties, ranging from the highly toxic and carcinogenic aflatoxins1 to insect antifeedants such as clerodin2 and azadirachtin 1. The furo[2,3b]pyran unit is conserved in the azadirachtin, whilst several clerodanes and aflaxtoxins contain the more common furo[2,3b]furan moiety. Many methods exist for the synthesis of the furo[2,3b]furans.3 In contrast, relatively few synthesis of the homologous furo[2,3b]pyrans have been reported.4 We wished to develop and work out a much flexible and relatively shorter route of the bioactive portion of the most potent insect antifeedant azadirachtin. Azadirachtin5 belongs to the C-seco- limonoid group of triterpinoids and is found in neem tree, or Indian lilac, Azadirachta indica. Although the first synthesis of the 1 is yet to be accomplished, nevertheless the biological testing has so far relied upon the natural azadirachtin, their chemically modified fragments, and a few synthetic analogs. The simple compounds 2 and 3, components of the 1, have been synthesized and screened for antifeedant activity.6 Both of these compounds were found to be active against African leaf worm Spodoptera lottoralis. The compound 3 was found to be as potent as the natural product 1 itself at 10 ppm and 1 ppm concentrations. This finding suggested that the
