Short and Efficient Synthesis of Cryptophycin Unit A

• Published in: Organic letters Vol. 9; no. 5; pp. 817 - 819
• Main Authors: Eissler, Stefan, Nahrwold, Markus, Neumann, Beate, Stammler, Hans-Georg, Sewald, Norbert
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.03.2007; Amer Chemical Soc
• Subjects: Aldehydes - chemistry; Chemistry; Chemistry, Organic; Crystallography, X-Ray; Depsipeptides - chemical synthesis; Depsipeptides - chemistry; Models, Molecular; Molecular Structure; Peptides, Cyclic - chemical synthesis; Peptides, Cyclic - chemistry; Physical Sciences; Science & Technology; SPONGE DYSIDEA-ARENARIA; ARENASTATIN-A; POTENT CYTOTOXIC DEPSIPEPTIDE; ASYMMETRIC DIHYDROXYLATION
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/ol063032l

Two short synthetic approaches toward cryptophycin unit A comprise a catalytic asymmetric dihydroxylation as the sole source of chirality, while all further stereogenic centers are introduced under substrate control. The key step of the first route is a vinylogous Mukaiyama aldol addition, which introduces the α,β-unsaturated ester moiety with defined configuration at the δ-carbon atom. Likewise, allylation with allyltributylstannane diastereoselectively gives the homoallylic alcohol that can be converted by a metathesis reaction to a unit A precursor.