Enzymatic desymmetrization of 1,1′-methylenedi[(1R,1′S,3R,3′S,5S,5′R)-3-hydroxy-8-oxabicyclo[3.2.1]oct-6-ene-1-yl]: novel precursors of long chain polyketides

meso-1,1′-Methylenedi[(1R,1′S,3R,3′S,5S,5′R)-3-hydroxy-8-oxabicyclo[3.2.1]oct-6-ene-1-yl] 14 obtained through the [4+3]-cycloaddition of 2,2′-methylenedifuran to oxyallyl cation, followed by reduction, has been desymmetrized by means of a lipase catalyzed transesterification to afford (1S,3S,5S)-1-{[(1R,3R,5R)-3-hydroxy-8-oxabicyclo[3.2.1]oct-6-en-yl]methyl}-8-oxabicyclo[3.2.1]oct-6-en-3-yl acetate (−)-15 (89% ee). This compound was transformed into aromatic ester derivatives for establishing the absolute configuration.

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(1S,3S,5S)-1-{[(1R,3R,5R)-3-Hydroxy-8-oxabicyclo[3.2.1]oct-6-en-1-yl]methyl}-8-oxabicyclo[3.2.1]oct-6-en-3-yl acetateC17H22O5Ee 89%[α]58923=-8 (c 0.46, CHCl3)Source of chirality: lipase from Candida cylindraceaAbsolute configuration: 1S,1′R,3S,3′R,5S,5′R

(1R,6R)-6-(Acetyloxy)-4-({(4S,6S)-4,6-bis[(4-methoxybenzoyl)oxy]cyclohept-1-en-yl}methyl)cyclohept-3-en-1-yl 4-methoxybenzoateC41H44O11Ee 89%[α]58923=+44 (c 0.47, CHCl3)Source of chirality: lipase from Candida cylindraceaAbsolute configuration: 1R,4′S,6R,6′S

(1R,3R,5R)-1-{[(1S,3S,5S)-3-Hydroxy-8-oxabicyclo[3.2.1]oct-6-en-1-yl]methyl}-8-oxabicyclo[3.2.1]oct-6-en-3-yl 2,2-dimethylpropanoateC20H28O5Ee 89%[α]58923=+8 (c 0.49, CHCl3)Source of chirality: lipase from Candida cylindraceaAbsolute configuration: 1R,1′S,3R,3′S,5R,5′S

(1S,6S)-4-({(4R,6R)-4,6-Bis[(4-methoxybenzoyl)oxy]cyclohept-1-en-1-yl}methyl)-6-[(2,2-dimethylpropanoyl)oxy]cyclohept-3-en-1-yl 4-methoxybenzoateC44H50O11Ee 89%[α]58923=-35 (c 0.55, CHCl3)Source of chirality: lipase from Candida cylindraceaAbsolute configuration: 1S,4′R,6S,6′R