Leucascandrolide a: synthesis and related studies.
The total synthesis of the biologically active marine natural product leucascandrolide A is reported. A convergent strategy is employed, allowing for the rapid assembly of the macrolide moiety. Key steps of our approach include the diastereoselective addition of a zinc alkynilide to (R)-isopropylidene glyceraldehyde, the enantioselective copper(I) fluoride catalyzed aldol addition of a TMS-dienolate to crotonaldehyde, and the formation of a 2,6-trans-substituted tetrahydropyran by selenium-mediated intramolecular cyclization. Moreover, dramatic solvent effects observed in the macrolactonization reaction suggest that hydrogen-bonding effects play a critical role. An improved route to a key intermediate of our synthesis is documented.
Fettes
Alec
A
Laboratorium für Organische Chemie, ETH Hönggerberg, Wolfgang Pauli Strasse 10, CH-8093 Zürich, Switzerland.
Carreira
Erick M
EM
D000818:Animals; D003500:Cyclization; D006860:Hydrogen Bonding; D008956:Models, Chemical; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D012717:Sesquiterpenes; C408748:leucascandrolide A