Synthetic efforts toward fumonisin analog were described. These are accomplished via amino acid Schiff base methodology. These efforts can be divided three major phases. First, tandem reductive alkylation with DIBAL/TRIBAL and different types of organo-lithium or Grignard nucleophiles provided threo-amino alcohol with excellent stereoselecitivites (2-27:1). The reductive alkylation utilized most hydrocarbon nucleophiles, e.g. alkyl-, vinyl-, alkenyl-, phenyl-, and dienyl-, and afforded high selectivites unless donor solvents (e.g. THF and Et2O) were used. Second, syntheses of the protected threo-γ-amino-β-hydroxy aldehydes and their stereoselectivities were introduced. The reductive alkylated threo-amino allyl alcohol was transformed via Brown’s hydroboration/oxidation protocol with 9-BBN, followed by TEMPO oxidation to give the resultant aldehydes in reasonable yields. Then, TBDPS and Schiff base protected aldehyde was coupled with phenyl- and decyl Grignard reagents to obtain predominant 3,5-anti-diols (ca. 80:20 anti:syn), characterized by ¹³C NMR analysis of Rychnovsky’s 1,3-acetonide groups. Products can be useful analogues for fumonisin and 5-hydroxy-sphingosine due to their structural similarity. Third stage involved the synthesis of C₁₁-C₂₀ fragment analog of fumonisin. Chiral auxiliaries (e.g. Evans and Myers) were administrated for stereoselective methylation, Sharpless asymmetric dihydroxylation in the presence of (DHQ)2PHAL catalyst was performed to form 1,2- syn-diols, and the manipulation of protection/deprotection and Finklestein reaction furnished C₁₁-C₂₀ fragment analog of fumonisin.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/193674 |
| Date | January 2009 |
| Creators | Kim, Shang U |
| Contributors | Polt, Robin L, Polt, Robin L, Mash, Eugene, Pyun, Jeffrey, Zheng, Zhiping, Smith, Mark |
| Publisher | The University of Arizona. |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | text, Electronic Dissertation |
| Rights | Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. |
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