Chiral building-blocks by chemoenzymatic desymmetrization of 2-ethyl-1,3-propanediol for the preparation of biologically active natural products

2-Ethyl-1,3-propanediol 1 and its related di-O-acetate 2 were desymmetrized by partial chemoenzymatic acetylation and deacetylation, by Pseudomonas fl uorescens lipase (Amano P.; PFL), to (R)-1-O-acetyl-2-ethyl-1,3-propanediol 3. On treatment of 3 with I-2/Ph3P/imidazole the related (S)-1-O-acetyl-2- ethyl-3-iodopropanol 4 was obtained and transformed into the corresponding triphenylphosphonium salt 5. Reaction of [(S)-3-acetoxy-2-ethylpropylidene] triphenylphosphorane 6, prepared from 5, with 2,3 :4,5-di-O-isopropylidene -beta-D-arabino-hexos-2-ulopyranose 7 gave (2)-3-C-acetoxymethyl-1,2,3,4,5- pentadeoxy-6,7:8,9-di-O-isopropylidene-beta-D-manno-dec-4-ene-6-ulo-6,10-py ranose 8 which was hydrogenated to 9 and subsequently deacylated to 10. Tre atment of 10 with Me2CO/H+ caused a rearrangement to (3R,4R,5S,6R,9R)-9-eth yl-5-hydroxy-3,4-isopropylidenedioxy-1,7-dioxaspiro[5.5]undecane 11, which closely matched the skeleton of the talaromycins. (C) 1999 Elsevier Science Ltd. All rights reserved.