Asymmetric syntheses of methyl N,O-diacetyl-D-3-epi-daunosaminide and methyl N,O-diacetyl-D-ristosaminide

J Org Chem. 2013 Dec 20;78(24):12397-408. doi: 10.1021/jo4020563. Epub 2013 Dec 4.

Abstract

Ab initio asymmetric syntheses of methyl N,O-diacetyl-D-3-epi-daunosaminide and methyl N,O-diacetyl-D-ristosaminide, employing diastereoselective epoxidation and dihydroxylation, respectively, of alkyl (3S,αR,Z)-3-[N-benzyl-N-(α-methylbenzyl)amino]hex-4-enoates as the key steps, are reported. The requisite substrates were readily prepared using the conjugate additions of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to methyl and tert-butyl (E)-hexa-2-en-4-ynoates followed by diastereoselective alkyne reduction. syn-Dihydroxylation using OsO4 proceeded under steric control on the 4Re,5Re face of the olefin to give the corresponding diol, which subsequently underwent lactonization. Meanwhile, epoxidation using F3CCO3H in conjunction with F3CCO2H proceeded on the opposite 4Si,5Si face of the olefin under hydrogen-bonding control from the in situ formed ammonium ion. Treatment of the intermediate epoxide with concd aq H2SO4 promoted highly regioselective ring-opening (distal to the in situ formed ammonium moiety) to give the corresponding diol (completing overall the formal anti-dihydroxylation of the olefin), which then underwent lactonization under the reaction conditions. Elaboration of these diastereoisomeric lactones through hydrogenolysis, N-Boc protection, reduction, methanolysis, and acetate protection gave methyl N,O-diacetyl-D-3-epi-daunosaminide and methyl N,O-diacetyl-D-ristosaminide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Esters / chemical synthesis*
  • Esters / chemistry
  • Hexosamines / chemical synthesis*
  • Hexosamines / chemistry
  • Molecular Conformation
  • Stereoisomerism

Substances

  • Esters
  • Hexosamines
  • methyl N,O-diacetyl-D-3-epi-daunosaminide
  • methyl N,O-diacetyl-D-ristosaminide