TOTAL SYNTHESIS OF THE ANTHELMINTIC MACROLIDE AVERMECTIN B1A

S V LEY, A ARMSTRONG, D DIEZMARTIN, M J FORD, P GRICE, J G KNIGHT, H C KOLB, A MADIN, C A MARBY, S MUKHERJEE, A N SHAW, A M Z SLAWIN, S VILE, A D WHITE, D J WILLIAMS, M WOODS

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125 Citations (Scopus)

Abstract

A highly convergent total synthesis of the anthelmintic macrolide avermectin B1a 1 is described. The key features of this synthesis include the introduction of the C(11)-C(15) portion by selective ring opening of a symmetrical 1,4-bis-epoxide 4 followed by reaction with the anion derived from the 3-methyl-2-(1-methylpropyl)-6-phenylsulphonylpyran 3 to afford the 'northern' C(11)-C(25) fragment 39. Coupling of the derived C(11)-C(25) aldehyde unit 42 with a C(1)-C(10) 'southern' fragment 2 was achieved via a novel deconjugative vinyl sulphone anion sequence. Macrolactonisation and subsequent introduction of the 3,4-double bond gave the aglycone portion 51. The oleandrosyloleandrose disaccharide was introduced by a novel silver-mediated coupling between the 5-acetylated aglycone 70 and the thiocarbonylimidazolide 69. Final deacetylation was accomplished using Super-Hydride to give the natural product 1.

Original languageEnglish
Pages (from-to)667-692
Number of pages26
JournalJournal of the Chemical Society, Perkin Transactions 1
Issue number4
Publication statusPublished - Apr 1991

Keywords

  • RADICAL CYCLIZATION APPROACH
  • FERN GLYCOSIDE OSMUNDALIN
  • STRATEGY EN ROUTE
  • 3,4-DIHYDRO-2H-PYRAN APPROACH
  • HEXAHYDROBENZOFURAN SUBUNIT
  • NATURAL (-)-OSMUNDALACTONE
  • AGLYCONE OSMUNDALACTONE
  • ORGANIC-SYNTHESIS
  • MILBEMYCINS
  • (+)-MILBEMYCIN-BETA-3

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