Diastereodivergent strategies for the synthesis of homochiral aculeatins.
We report concise and stereocontrolled syntheses of aculeatins (-)-A, (+)-B, (+)-D, and (+)-6-epi-D. Diastereodivergent 1,3-inductions in Mukaiyama aldol coupling contribute to reduce steps and to increase flexibility with reactants having sterically restricted proximal substituents (i.e., CH2), involving either a good anti or a moderate syn 1,3-induction, depending on the nature of protecting group (P). In addition, the 3,5-syn-diol-ketone resulting from concomitant deprotection of the beta-alkoxy (Tr = trityl) group proves to be remarkably stable whereas the 3,5-anti diastereoisomer cyclizes spontaneously to the corresponding tetrahydropyran hemiketal, thus enabling a useful and facile separation. The second part of our study is devoted to improving the yield and the diastereoselectivity of the final phenolic oxidation reaction leading to aculeatins.
Peuchmaur
Marine
M
Département de Pharmacochimie Moléculaire, UMR 5063 CNRS/Université Joseph Fourier, ICMG FR 2607 CNRS, Bâtiment E, Bâtiment André Rassat, 470 rue de la Chimie, 38 041 Grenoble cedex 9, France.
Wong
Yung-Sing
YS
D000473:Alkanes / Q000138:chemical synthesis* / Q000737:chemistry; D001554:Benzene / Q000737:chemistry; D002412:Cations / Q000737:chemistry; D003500:Cyclization; D004987:Ethers / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010636:Phenols / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000473:Alkanes; D002412:Cations; D004987:Ethers; D010636:Phenols; D013141:Spiro Compounds; D001554:Benzene