Total Synthesis of Cryptophycin A and Analogs
Abstract
The synthesis of C3 and ClO analogs of Cryptophycin A and Arenastatin A is currently under way. The C3 stereocenter can be inverted by substituting (R)-leucic acid with (s)-leucic acid to determine whether the R configuration at C3 is required for bioactivity. To date, the southern half of C3 epi-Arenastatin A has been prepared. The ClO analogs will be prepared to determine the necessity of the aromatic C4' oxygen on the ClO side chain. Chlorinated phenylalanine ClO analogs are being prepared by chlorination of (R)-tyrosine, followed by deoxygenation. The synthesis of the phenylalanines necessary for the synthesis of the ClO analogs has been carried out and is currently being optimized. The synthesis and scale up of the Cryptophycin A and Arenastatin A ClO tyrosine building blocks has been completed. Studies for the stereoselective epoxidation in the final epoxidation to form Arenastatin A and Cryptophycin A, are being examined. Thus far, in situ chiral dioxiranes and a sterically hindered peracid have been tested.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 1999
- Accession Number
- ADA381236
Entities
People
- Gunda Georg
- Suzanne B. Buck
Organizations
- University of Kansas