A chemoenzymatic asymmetric synthesis of methyl (6S,13R)-6,13-dihydroxytetradeca-(2E,4E,8E)-trienoate, a component of Mycosphaerella rubella

The first asymmetric synthesis of (6S,13R)-6,13-dihydroxytetradeca-(2E,4E,8E)-trienoate has been developed. The key steps of the synthesis were the use of an efficient lipase-catalyzed acylation, a chiral template-driven enantiocontrolled allylation for introducing the stereogenic centers, and a cross-metathesis for controlling the C-8 olefin geometry.

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(S)-6-Hepten-2-olC7H14O[α]D22=+6.2 (c 1.0, CHCl3)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (S)

(R)-2-Acetoxyhept-6-eneC9H16O2[α]D22=-1.5 (c 1.58, CHCl3)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (R)

(R)-6-Hepten-2-olC7H14O[α]D22=-6.8 (c 1.22, CHCl3)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (R)

(R)-2-(tert-Butyldiphenylsilyloxy)hepte-6-eneC28H32OSi[α]D22=+13.2 (c 1.14, CHCl3)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (R)

(2R,3S,10R)-10-(tert-Butyldiphenylsilyloxy)-1,2-cyclohexanedioxyundec-5-en-3-olC33H48O4Si[α]D22=+18.8 (c 1.04, CHCl3)Source of chirality: lipase-catalyzed resolution and asymmetric reactionAbsolute configuration: (2R,3S,10R)

(2R,3S,10R)-3,10-Di-(tert-butyldiphenylsilyloxy)-1,2-cyclohexanedioxyundec-5-eneC49H66O4Si2[α]D22=+24.6 (c 1.12, CHCl3)Source of chirality: lipase-catalyzed resolution and asymmetric reactionAbsolute configuration: (2R,3S,10R)

(2R,3S,10R)-3,10-Di-(tert-butyldiphenylsilyloxy)undec-5-ene-1,2-diolC43H58O4Si2[α]D22=+13.1 (c 3.12, CHCl3)Source of chirality: lipase-catalyzed resolution and asymmetric reactionAbsolute configuration: (2R,3S,10R)

(2S,9R)-2,9-Di-(tert-butyldiphenylsilyloxy)dec-4-enalC42H54O3Si2[α]D22=+16.0 (c 0.861, CHCl3)Source of chirality: lipase-catalyzed resolution and asymmetric reactionAbsolute configuration: (2R,9R)

Methyl (6S,13R)-6,13-di-(tert-butyldiphenylsilyloxy)tetradeca-(2E,4E,8E)-trienoateC47H60O4Si2[α]D22=+8.9 (c 0.842, CHCl3)Source of chirality: lipase-catalyzed resolution and asymmetric reactionAbsolute configuration: (6S,13R)

Methyl (6S,13R)-6,13-dihydroxy)tetradeca-(2E,4E,8E)-trienoateC15H24O4[α]D22=+14.8 (c 0.618, MeOH)Source of chirality: lipase-catalyzed resolution and asymmetric reactionAbsolute configuration: (6S,13R)