Synthesis of sialic acids via desymmetrization by ring-closing metathesis.
Formal total syntheses of the naturally occurring deaminated sialic acids KDN (2), a potential oncofetal antigen, and N-acetylneuraminic acid (Neu5Ac, 1), the most naturally abundant sialic acid, have been accomplished in 46% and 9.3% overall yield, respectively, via a novel ketalization/ring-closing metathesis sequence. The rapid introduction of all oxygen and nitrogen functionality in a completely stereocontrolled manner exploited a rigid 6,8-dioxabicyclo[3.2.1]oct-2-ene template. The 2,7-anhydro-KDN derivative 40 served as an advanced intermediate in each of the two syntheses.
Voight
Eric A
EA
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706-1396, USA.
Rein
Christian
C
Burke
Steven D
SD
D000951:Antigens, Neoplasm / Q000737:chemistry; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D002855:Chromatography, Thin Layer; D003500:Cyclization; D015394:Molecular Structure; D019158:N-Acetylneuraminic Acid / Q000138:chemical synthesis; D019906:Nuclear Magnetic Resonance, Biomolecular; D012794:Sialic Acids / Q000032:analysis / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000951:Antigens, Neoplasm; D012794:Sialic Acids; C031192:oncofetal antigens; D019158:N-Acetylneuraminic Acid