Abstract
A concise, diastereoselective synthesis of (±)-fumagillol (3) and formal, enantioselective syntheses of the potent angiogenesis inhibitors fumagillin (1) and TNP-470 (2) are reported. The origin of asymmetry is a highly diastereoselective Diels-Alder reaction using a diene with a chiral oxazolidinone auxiliary. The stereochemical course of a key conjugate addition reaction is controlled by the cup-shaped architecture of a cis-fused bicyclic enal. Other key steps include a facile hetero-Claisen rearrangement and a site-selective Sharpless epoxidation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 156-166 |
| Number of pages | 11 |
| Journal | Chirality |
| Volume | 15 |
| Issue number | 2 |
| DOIs | |
| State | Published - 2003 |
| Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Catalysis
- Analytical Chemistry
- Pharmacology
- Drug Discovery
- Spectroscopy
- Organic Chemistry
Keywords
- Angiogenesis inhibitors
- Chiral auxiliary
- Conjugate addition
- Diastereo-selective cycloaddition
- Hetero-Claisen rearrangement
- Natural products
- Sharpless epoxidation
- Total synthesis