Fluorous mixture synthesis approach to natural product stereoisomers: Synthesis of both enantiomers of pyridovericin and mappicine and eight isomers of murisolin

In Chapter 1, practical synthetic methods for synthesis of a family of new fluorous monophosphines and bisphosphines are developed. The fluorous monophosphines are used in platinum-catalyzed allylations of a fluorous allylstannane with aldehydes and the bisphosphines are used in palladium-catalyzed Heck vinylations of enamides with vinyl triflates. Fluorous solid phase extraction is used to separate the fluorous phosphines and metal-complexes from the organic compounds.; In Chapter 2, the concept of “quasiracemic synthesis” is introduced to combine the advantages of racemic synthesis and asymmetric synthesis. Two enantiomeric starting materials are tagged with fluorous groups with different chain lengths and the tagged products mixed to form a quasiracimic mixture, which is used for a synthetic sequence. At the end of the sequence, fluorous chromatography is used to resolve the final quasiracemic mixture into two individual components, which are then detagged to provide the enantiomeric products. The concept is illustrated with the total synthesis of natural products (R)-pyridovericin, (S)-mappicine and their enantiomers. Both enantiomers of mappicine are obtained in enantiopure form in one synthesis while those of pyridovericin have enantiomeric excess of around 15%. The absolute configuration of pyridovericin is assigned as R for the first time.; In Chapter 3, the quasiracemic synthesis technique is extended to the synthesis of diastereomers of the natural product murisolin. Four stereoisomeric starting materials are tagged with fluorous groups with different chain lengths and mixed to form the starting mixture. Eight isomers of murisolin are synthesized in two reaction sequences by using this technique. Three synthetic isomers have identical 1H NMR, 13C NMR spectroscopic data as the natural products murisolin, murisolin A and 16,19-cis -murisolin, respectively. The results of biological tests of the eight synthetic isomers are presented.