The new thiazole amino acid (gln)Thz, found to occur as one unit of the marine sea hare cyclic pentapeptide dolastatin 3, has been synthesized from L-glutamic acid by the route 2 → 10e. The synthesis of Z-L-isoglutamine (4) was improved by selective ammonolysis of anhydride 3 at -60 °C. A variety of reaction conditions were found to cause complete racemization during the Hantzsch thiazole synthesis step (9→ 10). Deuterium labeling experiments indicated loss of the chiral center prior to formation of the thiazole system and suggested an imine-enamine type equilibration involving intermediates A ⇌ B (Scheme II). The N-benzyloxycarbonyl derivative (10d) of (gln)Thz was partially resolved by employing brucine.
ASJC Scopus subject areas
- Organic Chemistry