Stereocontrolled synthesis of (-)-macrolactin A.
The total synthesis of (-)-macrolactin A, a 24-membered macrolide, has been achieved using a newly developed 1,3-diol synthon for the introduction of two key stereogenic centers. The synthon was derived from sequential use of the Noyori asymmetric reduction followed by chiral sulfoxide methodology. Tellurium-derived cuprate organometallics offered an efficient and highly stereoselective means for installation of the C8 Z/E-diene, while the C15 E/E-segment was derived from a Julia-Lythgoe olefination. Yamaguchi lactonization was used to secure the macrocycle in a convergent approach with the longest linear sequence of 19 steps from Noyori alcohol 6.
Marino
Joseph P
JP
Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
McClure
Michael S
MS
Holub
David P
DP
Comasseto
João V
JV
Tucci
Fabío C
FC
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology; D018942:Macrolides / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013831:Thiamine / Q000031:analogs & derivatives / Q000737:chemistry
D000903:Antibiotics, Antineoplastic; D000998:Antiviral Agents; D018942:Macrolides; C453563:N1'-methyl-2-(1-hydroxybenzyl)thiamin; D013831:Thiamine