Total synthesis of rutamycin B, a macrolide antibiotic from Streptomyces aureofaciens.
Rutamycin B (2) was synthesized from three principal subunits, spiroketal 75, keto aldehyde 83, and aldehyde 108. First, triol 62 was assembled by Julia coupling of sulfone 56 with aldehyde 58 followed by an acid-catalyzed spiroketalization. The three hydroxyl functions of 62 were successfully differentiated, leading to phosphonate 75. The latter was condensed in a Wadsworth-Emmons reaction with 83, prepared in six steps from (R)-aldehyde 76, to give 92. Coupling of the titanium enolate of 92 with 108 afforded Felkin product 109 with high stereoselectivity in a process that is critically dependent on the presence of the p-methoxybenzyl ether in the aldehyde. Transformation of 109 via aldehyde 116 to vinylboronate 122 was followed by macrocyclization under Suzuki conditions to yield 123. Exhaustive desilylation of the latter yielded rutamycin B.
White
J D
JD
Department of Chemistry, Oregon State University, Corvallis, Oregon 97331-4003, USA. james.white@orst.edu
Hanselmann
R
R
Jackson
R W
RW
Porter
W J
WJ
Ohba
Y
Y
Tiller
T
T
Wang
S
S
D000447:Aldehydes / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D012427:Rutamycin / Q000138:chemical synthesis*; D013304:Streptomyces aureofaciens / Q000737:chemistry*
D000447:Aldehydes; D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D012427:Rutamycin