New tandem reactions for the synthesis ofnitrogen containing natural products

QD Chemistry;RM Therapeutics. Pharmacology;RS Pharmacy and materia medica

Zaed, Ahmed Mohamed Faraj ; Sutherland, Andrew

University:University of Glasgow

Department:School of Chemistry

关键词: Tandem Process:Ring Closing Metathesis ReactionOverman RearrangementMOM-ether directed overman rearrangement;   

Others  :  http://theses.gla.ac.uk/3927/1/2012ZaedPhD1.pdf

来源: University of Glasgow

【 摘 要 】

AbstractDuring the course of the studies outlined in this thesis, a new approach for the synthesis of the tropane alkaloid, (±)-physoperuvine has been developed using a highly efficient one-pot tandem process which involved the Overman rearrangement and a ring closing metathesis reaction. An asymmetric one-pot tandem process has also been employed for the synthesis of the natural product, (+)-physoperuvine. This methodology was also applied to the generation of a late-stage intermediate that could be used in the synthesis of carbocyclic nucleosides, such as noraristeromycin.In the second part of this thesis, an ether-directed Pd(II)-catalysed Overman rearrangement which had previously been developed by the Sutherland group was applied in conjunction with a cross-metathesis reaction for the stereoselective synthesis of the guanidine alkaloid, (+)-monanchorin in a fourteen-step synthesis.Further employment of this process provided the first synthesis of clavaminol A, C and H from (R)-glycidol in a rapid and efficient manner. In a similar fashion, (2S,3R)-enantiomers were also synthesised from (S)-glycidol. In addition to this, using similar chemistry, an intermediate protected enone was prepared using a cross-metathesis reaction as the second key step in an approach towards the synthesis of an NO-inhibitor.