Novel methods for the conversion of carbohydrates to carbocycles
thesisposted on 15.12.2014, 10:35 by David John. Holt
The 'chiron' approach to the synthesis of chiral target molecules from carbohydrates is now a well established component in the armoury of organic chemistry. A key element of this strategy is the range of methods available for the synthesis of cyclic compounds, which can include some or all of the carbons of the original carbohydrate (Chapter 1).;The cyclopentaannulated sugar derivative 1, a product of intramolecular aldol condensation, was treated with N-bromosuccinimide (NBS), followed by activated zinc shot, to furnish a ca 4:1 mixture of cyclopentane derivatives 2 and 3 (Chapter 2). (Fig. 6078A).;Ring closing metathesis has been applied to a series of substituted glucose derivatives, employing the Grubbs catalyst 4, to produce fused enantiomerically pure annulated sugars 5, containing five- to eight-membered carboyclic rings (Chapter 3). Copper(I) triflate catalyzed intramolecular [2+2] photocylization has also been studied as a method for carbohydrate annulation (Chapter 4). Photoannulation of 1,6-diene glucose derivatives leads efficiently to fused tetracyclic enantiomerically pure products, e.g.6. Investigations into the fragmentation of these annulated sugars, utilizing NBS and zinc methodology, in an attempt to synthesize enantiomerically pure carbocycles, are also described. (Fig. 6078B).;As a continuation of work in the Jenkins group, directed towards the synthesis of a chiral taxoid from glucose, model studies were undertaken to test the viability of an enone to diene conversion, utilizing selenium chemistry (Chapter 5). Even though model studies showed this conversion to be successful, the enone 7 produced the diene 8 in a very poor yield (12%). Alternative methods for diene construction were investigated, including Wittig and Stille chemistry, with a limited amount of success. (Fig. 6078C).