Self-consistent synthesis of the squalene synthase inhibitor zaragozic acid C via controlled oligomerization.
Despite the prevalence of repeating subunits in chiral natural products, stereocontrolled oligomerization is a largely unexplored strategy for construction of carbon skeletal frameworks. This report describes the use of silyl glyoxylates as dipolar glycolic acid synthons in a controlled oligomerization reaction for the efficient construction of the squalene synthase inhibitor zaragozic acid C. This new methodology allows rapid, stereocontrolled formation of the carbon skeleton with a desirable protecting group scheme while minimizing functional group repair and oxidation state manipulations.
Nicewicz
David A
DA
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, USA.
Satterfield
Andrew D
AD
Schmitt
Daniel C
DC
Johnson
Jeffrey S
JS
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D002244:Carbon / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors*; D006016:Glycolates / Q000737:chemistry; D006038:Glyoxylates / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D015394:Molecular Structure; D013237:Stereoisomerism
D019086:Bridged Bicyclo Compounds, Heterocyclic; D006016:Glycolates; D006038:Glyoxylates; C079090:zaragozic acid C; C031149:glycolic acid; D002244:Carbon; D013186:Farnesyl-Diphosphate Farnesyltransferase