A major goal of the Leighton group is the synthesis of biologically relevant polyketide natural products. Among the most potent and chemically intriguing member of this class is spongistatin 1. This molecule has interested biologists and chemists for more than two decades. In this thesis, we report a highly practical and efficient synthesis of the EF fragment of spongistatin 1. This relied on the rapid introduction of a complex stereochemical array using double cross-metathesis/Sharpless asymmetric dihydroxylation reactions to quickly build the F-ring of spongistatin. The six contiguous stereocenters of the F-ring were established in just five steps. A new one-pot asymmetric strained-silane mediated allylation was developed that was greatly improved over previous methods in regards to practicality and substrate scope. This methodology was used to introduce the sensitive chlorodiene side chain. Finally, completion of the EF fragment led to the synthesis of a spongistatin 1 analog, using our previously developed redesigned ABCD fragment.
| Identifer | oai:union.ndltd.org:columbia.edu/oai:academiccommons.columbia.edu:10.7916/D8CN7G5P |
| Date | January 2017 |
| Creators | Infantine, Joshua Ross |
| Source Sets | Columbia University |
| Language | English |
| Detected Language | English |
| Type | Theses |
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