Chemoenzymatic resolution of cis- and trans-3,6-dihydroxy-α-ionone. Synthesis of the enantiomeric forms of dehydrovomifoliol and 8,9-dehydrotheaspirone

A straightforward synthesis of both enantiomers of cis- and trans-3-acetoxy-6-hydroxy-α-ionone is described. The title compounds are prepared by resolution of the diastereoisomerically pure racemic 3,6-dihydroxy-α-ionone isomers. The latter process is based on two steps. The first is the enantio- and regioselective lipase-mediated acetylation of diols to afford the corresponding 3-acetoxy-derivatives. The second is the fractional crystallization of the latter compounds that increase their enantiomeric purity. These building blocks were used for the synthesis of both enantiomeric forms of the natural norterpenoids dehydrovomifoliol 3 and 8,9-dehydrotheaspirone 5. The latter compound is a natural flavor and its odor properties were evaluated by professional perfumers.

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(+)-(6S)-DehydrotheaspironeC13H18O2Ee = 98% (chiral GC analysis)[α]D20=+35 (c 1, CHCl3)Source of chirality: lipase-mediated resolution and fractional crystallizationAbsolute configuration: (6S)

(−)-(5R,8S)-2,6,10,10-Tetramethyl-1-oxa-spiro[4.5]deca-2,6-dien-8-yl acetateC15H22O3Ee = 97%[α]D20=-17.4 (c 1, CHCl3)Source of chirality: lipase-mediated resolution and fractional crystallizationAbsolute configuration: (5R,8S)

(−)-(5S,8S)-2,6,10,10-Tetramethyl-1-oxa-spiro[4.5]deca-2,6-dien-8-yl acetateC15H22O3Ee = 98%[α]D20=-48.7 (c 1, CHCl3)Source of chirality: lipase-mediated resolution and fractional crystallizationAbsolute configuration: (5S,8S)

(+)-DehydrovomifoliolC13H18O3Ee = 98%[α]D20=+222 (c 0.5, CH2Cl2)Source of chirality: lipase-mediated resolution and fractional crystallizationAbsolute configuration: (6S)

(−)-(3S,6R)-3-Acetoxy-6-hydroxy-α-iononeC15H22O4Ee = 97%[α]D20=-198.8 (c 1, CHCl3)Source of chirality: lipase-mediated resolution and fractional crystallizationAbsolute configuration: (3S,6R)

(+)-(3S,6S)-3-Acetoxy-6-hydroxy-α-iononeC15H22O4Ee = 98%[α]D20=+164 (c 1, CHCl3)Source of chirality: lipase-mediated resolution and fractional crystallizationAbsolute configuration: (3S,6S)