A Straightforward, Highly Stereoselective Synthesis of Protected Isostatine Derivatives

✍ Scribed by Patricia Castejón; Albert Moyano; Miquel A. Pericàs; Antoni Riera

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 795 KB
• Volume: 2
• Category: Article
• ISSN: 0947-6539
• DOI: 10.1002/chem.19960020816

✦ Synopsis

A novel strategy for the synthesis of isostatine derivatives has been developed. Contrary to previous approaches to isostatine, a non-proteinogenic amino acid that is an essential component of the didemnins, the present synthesis does not require the intermediacy of the expensive amino acid D-do-isoleucine, the starting material being commercially available enantiopure (S)-2-methyl-l-butanol.

Steps in the sequence include catalytic asymmetric epoxidation, regioselective ti-tanium-promoted opening of an epoxy alcohol with an ammonia equivalent, stereospecific generation of an N-Bocamino epoxide and its nucleophilic opening by a cyanide anion. Application of this method has permitted the enantioselective preparation of isostatine methyl ester and, for the first time, of isostatine amide, both in fully protected form.