A second-generation synthesis of the C1-C28 portion of the altohyrtins (spongistatins).
A practical second-generation synthesis of an advanced intermediate in our total synthesis of altohyrtin C (spongistatin 2) has been developed. A new approach to the C1-C15 (AB) portion features a vinyllithium addition to an aldehyde followed by a palladium-catalyzed allylic reduction to install the troublesome C13-C15 segment. Our general approach to the C16-C28 (CD) spiroketal has been retained, but some improvements have been made. Most notably, the kinetically controlled CD-spiroketalization reaction now proceeds in high yield with excellent diastereoselection. This new strategy uses the anti-aldol coupling used in our first-generation synthesis to join AB and CD fragments. A total of 9.6 g of intermediate 57 has been produced using this improved route.
Hubbs
Jed L
JL
Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley, California 94720, USA.
Heathcock
Clayton H
CH
D000970:Antineoplastic Agents / Q000138:chemical synthesis; D002384:Catalysis; D018942:Macrolides / Q000138:chemical synthesis*; D010165:Palladium / Q000737:chemistry; D013141:Spiro Compounds / Q000737:chemistry; D014753:Vinyl Compounds / Q000737:chemistry; D000095702:Polyether Toxins
D000970:Antineoplastic Agents; D018942:Macrolides; D010165:Palladium; D013141:Spiro Compounds; D014753:Vinyl Compounds; C409088:altohyrtin C; D000095702:Polyether Toxins