The recently isolated bacterial metabolites, belactosins A-C from a fermentation
broth of Streptomyces sp. UCK14, uniquely contain a β-lactone dipeptide motif and
exhibit anticancer activities. The enantioselective synthesis of (-)-belactosin C and
derivatives was accomplished in a concise manner employing the tandem, Mukaiyama
aldol-lactonizaton (TMAL) process and test their bioactivities. . One approach involved
a distal double diastereoselective TMAL reaction with a dipeptide glyoxamide, whereas
a second approach involved amide coupling of a dipeptide with a β-lactone carboxylic
acid, obtained via the TMAL process employing a chiral silyl ketene acetal. Enzymatic
assays showed that the belactosins act as the dual inhibitors of the proteasome and the
thioesterase domain of fatty acid synthase.
Spongiolactone which uniquely contains a cyclopentyl-fused β-lactone was
isolated in 1986 from Spongi-onellagracilis No biological activity have been reported
for this compound; however, the acylating potential of the resident β-lactone warrants
screening for potential activity. After many setbacks in the synthesis of spongiolactone,
significant progress has been made. Importantly, NCAL process also enabled a concise construction of [3.2.0]-bicyclo β-lactone, which is the key structure in the
spongiolactone synthesis and only a few steps remained to complete the synthesis.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-3121 |
| Date | 15 May 2009 |
| Creators | Cho, Sung Wook |
| Contributors | Gabbai, Francois P., Romo, Daniel |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | Book, Thesis, Electronic Dissertation, text |
| Format | electronic, application/pdf, born digital |
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