Date of Graduation
2001
Document Type
Thesis
Degree Type
MS
Committee Chair
Kay M. Brummond
Abstract
A novel immunosuppressant, FR901483 (1) was discovered by a Fujisawa company, which was isolated from the fermentation broth of a fungal strain. It exerts a potent immunosuppressive activity in vitro and significantly prolongs graft survival time in the rat skin allograft model. Our group has postulated a novel synthetic approach to the target compound (1) that can be used for the preparation of a structurally diverse set of compounds. And our group has successfully synthesized the aminoaldehyde 42 that possesses the core structure of FR901483 using the tandem cationic aza-Cope rearrangement-Mannich cyclization strategy. In order to apply this strategy to the real system, a much more functionalized azaCope-Mannich cyclization precursor is required, we reasoned that this precursor could be derived from aldol reaction of the aldehyde of L-tyrosine and the monoprotected 1,4- cyclohexanedione. Aldol reaction of the α-amino aldehyde 110 with keto ketal 37b and LDA in THF at –78 °C for 2.5 hour afforded 40% of one major diastereomer 111 and 43% of other three diastereomers. To our delight, the major diastereomer 111 has the desired stereochemistry of FR901483 by X-ray crystallography. Further reactions were made to try to complete the total synthesis of FR901483.
Recommended Citation
Sha, Li, "A synthetic approach to FR901483." (2001). Graduate Theses, Dissertations, and Problem Reports (ETD). 10584.
https://researchrepository.wvu.edu/etd/10584