A practical synthesis of the F-ring of halichondrin B via ozonolytic desymmetrization of a C(2)-symmetric dihydroxycyclohexene.
C(2)-symmetric dihydroxycyclohexene 1 was desymmetrized via a one-pot Criegee ozonolysis/acylation protocol to afford acetal-lactone 2. Installation of the allyl side chain on the convex face of the bicyclic system and subsequent reduction provided the desired tetrahydrofuran 4 with the correct relative and absolute stereochemistries. Simple functional group manipulations led to the desired F-ring module 3 of halichondrin B.
Jiang
Lei
L
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706-1396, USA.
Martinelli
Joseph R
JR
Burke
Steven D
SD
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D004988:Ethers, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D018942:Macrolides; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D000095662:Polyether Polyketides
D000970:Antineoplastic Agents; D004988:Ethers, Cyclic; D007202:Indicators and Reagents; D018942:Macrolides; C070519:halichondrin B; D000095662:Polyether Polyketides