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
- Drug Discovery
- Analytical Chemistry
- Spectroscopy
- Catalysis
- Pharmacology
- Organic Chemistry
Keywords
- Angiogenesis inhibitors
- Chiral auxiliary
- Conjugate addition
- Diastereo-selective cycloaddition
- Hetero-Claisen rearrangement
- Natural products
- Sharpless epoxidation
- Total synthesis