Pederin : the degradative approach

Faller, Andrew (1988) Pederin : the degradative approach. University of Southampton, Doctoral Thesis.

Abstract

As an alternative to our earlier synthesis of Pederin (1) we have investigated a new strategy based on the degradative work of Cardani. This strategy has involved the synthesis of the aminal portion of (1) prior to the coupling of any two fragments thus, we hoped, avoiding problems with the instability of (1) and its immediate pre-cursors. We have prepared the lithio-dihydropyran (12) and sought to couple it with activated derivatives of 4'-benzoyl-mero-pederoic acid (37), synthesised by an extension of our earlier route to amide (35). Although successful on a variety of model systems we were unable to couple these fragments in the desired manner. A rationalisation, as yet unsubstantiated, is provided for these observations. We have sought an alternative way of taking advantage of having a pre-formed aminal centre before completion of the Pederin skeleton. We have concentrated our efforts on an approach via the intramolecular attack of an allyl silane onto an ester group (105) - (106). This approach to forming the lefthand tetrahydropyran ring of (1) appears unprecedented - since esters are usually insufficiently activated to undergo nucleophilic attack by allyl silane groups - however we hope that the activating effect of an α-keto group, required for the C-7 hydroxyl of (1), would overcome this problem. We have synthesised the required (model) β-dicarbonyl pre-cursor to (106) but have found ourselves unable to oxidise this to the linear tricarbonyl compound. Therefore we have been unable to attempt the ring closure reaction. Several schemes are suggested by which the problems in synthesising (106) may be overcome (DX86441)

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