Studies on the synthesis of bafilomycin A(1): stereochemical aspects of the fragment assembly aldol reaction for construction of the C(13)-C25) segment.
Highly stereoselective syntheses of aldols 8a-c corresponding to the C(13)-C(25) segment of bafilomycin A(1) were developed by routes involving fragment assembly aldol reactions of chiral aldehyde 6a and the chiral methyl ketones 7. A remote chelation effect plays a critical role in determining the stereoselectivity of the key aldol coupling of 6a and the lithium enolate of 7b. The protecting group for C(23)-OH of the chiral aldehyde fragment also influences the selectivity of the lithium enolate aldol reaction. In contrast, the aldol reaction of 6a and the chlorotitanium enolates of 7a,c were much less sensitive to the nature of the C(15)-hydroxyl protecting group. Studies of the reactions of chiral aldehydes with Takai's (gamma-methoxyallyl)chromium reagent 40 are also described. The stereoselectivity of these reactions is also highly dependent on the protecting groups and stereochemistry of the chiral aldehyde substrates.
Roush
William R
WR
Department of Chemistry, Indiana University, Bloomington 47405, USA. roush@umich.edu
Bannister
Thomas D
TD
Wendt
Michael D
MD
Jablonowski
Jill A
JA
Scheidt
Karl A
KA
D000447:Aldehydes / Q000138:chemical synthesis* / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D018020:Lithium Compounds / Q000737:chemistry; D018942:Macrolides; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism
D000447:Aldehydes; D000900:Anti-Bacterial Agents; D018020:Lithium Compounds; D018942:Macrolides; C111293:formamicin; C465999:hygrolidin; C036978:concanamycin A; C040929:bafilomycin A1