A short enantioselective synthesis of guggultetrol, a naturally occurring lipid

An enantioselective synthesis of the naturally occurring lipid, guggultetrol, is described with an overall yield of 24% starting from commercially available l-pentadecanol in ten linear steps. The key chiral-inducing steps include a Sharpless asymmetric epoxidation of allylic alcohol and a dihydroxylation of an α,β-unsaturated ester.

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[(2R,3R)-3-Tetradecyloxirane-2-yl]methanolC17H34O2Ee 98%; determined by 1H NMR analysis of Mosher’s ester[α]D25=+10 (c 0.6, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (2R,3R)

(2S,3R)-2-(Iodomethyl)-3-tetradecyloxiraneC17H33IO[α]D25=-20 (c 0.3, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (3S,2R)

(R)-Heptadec-1-ene-3-olC17H34O[α]D25=-16.7 (c 0.6, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (R)

(R)-3-(Methoxymethoxy)heptadec-1-eneC19H38O2[α]D25=+64 (c 1, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (R)

(R)-trans-Ethyl-4-(methoxymethoxy)octadec-2-enoateC22H42O4[α]D25=+30 (c 0.8, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (R)

(2R,3R,4R)-Ethyl-2-3-dihydroxy-4-(methoxymethoxy)octadecanoateC22H44O6[α]D25=-18 (c 2, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (2R,3R,4R)

(2S,3R,4R)-4-(Methoxymethoxy)octadecane-1,2,3-triolC22H44O6[α]D25=-40 (c 0.4, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (2S,3R,4R)