A chemoenzymatic asymmetric synthesis of the hydroxy acid segment of schulzeines B and C

A chemoenzymatic asymmetric synthesis of the title compound was developed by a building-block approach. The key steps of the synthesis were (i) an enantioselective lipase-catalyzed acylation of a secondary alcohol, (ii) an efficient diastereoselective addition of an alkyl-lithium reagent to a glyceraldehyde derivative, (iii) conversion of an epoxide to a one-carbon homologated allylic alcohol via a sulphorane addition, and (iv) a cross metathesis between two chiral allylic alcohols and subsequent functionalization to obtain the ethyl ester of the hydroxy acid unit of the schulzeines.

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(R)-14-(tert)-Butyldiphenylsilyloxy tetradec-1-en-3-olC30H46O2Si[α]D22=-3.0 (c 1.07, CHCl3)Source of chirality: lipase catalyzed resolutionAbsolute configuration: (R)

(S)-3-Acetoxy-14-(tert)-butyldiphenylsilyloxytetradec-1-eneC32H48O3Si[α]D22=-4.4 (c 1.11, CHCl3)Source of chirality: lipase catalyzed resolutionAbsolute configuration: (S)

(S)-12-Acetoxytetradec-13-en-1-olC16H30O3[α]D22=-6.1 (c 1.08, CHCl3)Source of chirality: lipase catalyzed resolutionAbsolute configuration: (S)

(S)-12-Acetoxytetradec-13-enalC16H28O3[α]D22=-4.6 (c 1.04, CHCl3)Source of chirality: lipase catalyzed resolutionAbsolute configuration: (S)

Ethyl (S)-14-acetoxyhexadeca-2E,15-dienoateC20H34O4[α]D22=-5.4 (c 1.03, CHCl3)Source of chirality: lipase catalyzed resolutionAbsolute configuration: (S)

(2R,3S)-1,2-Cyclohexylidenedioxytridecan-3-olC19H36O3[α]D22=+5.1 (c 1.14, CHCl3)Source of chirality: cyclohexylideneglyceraldehydeAbsolute configuration: (2R,3S)

(2R,3S)-3-Benzyloxy-1,2-cyclohexylidenedioxytridecaneC26H42O3[α]D22=+5.0 (c 1.16, CHCl3)Source of chirality: cyclohexylideneglyceraldehydeAbsolute configuration: (2R,3S)

(2R,3S)-3-Benzyloxy-tridecane-1,2-diolC20H34O3[α]D22=+7.3 (c 1.12, CHCl3)Source of chirality: cyclohexylideneglyceraldehydeAbsolute configuration: (2R,3S)

(2S,3S)-3-Benzyloxy-1,2-epoxytridecaneC20H32O2[α]D22=-22.5 (c 1.28, CHCl3)Source of chirality: cyclohexylideneglyceraldehydeAbsolute configuration: (2S,3S)

(3S,4S)-4-Benzyloxytetradec-1-en-3-olC21H34O2[α]D22=+3.1 (c 0.980, CHCl3)Source of chirality: cyclohexylideneglyceraldehydeAbsolute configuration: (3S,4S)

Ethyl (14S,17S,18S)-14-acetoxy-17-hydroxy18-benzyloxyoctacosa-2E,15E/Z-dienoateC39H64O6[α]D22=-9.3 (c 1.03, CHCl3)Source of chirality: lipase catalyzed resolution and cyclohexylideneglyceraldehydeAbsolute configuration: (14S,17S,18S)

Ethyl (14S,17S,18S)-14-acetoxy-17,18-dihydroxyoctacosanoateC32H62O6[α]D22=-13.2 (c 1.14, CHCl3)Source of chirality: lipase catalyzed resolution and cyclohexylideneglyceraldehydeAbsolute configuration: (14S,17S,18S)

Ethyl (14S,17S,18S)-14,17,18-trihydroxyoctacosanoateC30H60O5[α]D22=-11.7 (c 0.912, CHCl3)Source of chirality: lipase catalyzed resolution and cyclohexylideneglyceraldehyde