Diastereoselective synthesis of (+)-nephrosterinic acid and (+)-protolichesterinic acid

A diastereoselective synthesis of (+)-nephrosterinic acid and (+)-protolichesterinic acid, common members of the paraconic acids is described. The synthesis is based on a diastereoselective orthoester Johnson–Claisen rearrangement of a (Z)-allyl alcohol with a vicinal dioxolane moiety as key steps. The synthesis is completed in 10 steps and with overall yields of 15.9% for (+)-nephrosterinic acid and 16.4% for (+)-protolichesterinic acid.

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(2R,3S)-Ethyl 2,3-dihydroxytridecanoateC15H30O4[α]D25=-9.9 (c 1.26, CHCl3)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (2R,3S)

(2R,3S)-Ethyl 2,3-dihydroxypentadecanoateC17H34O4[α]D25=-7.8 (c 1.4, CHCl3)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (2R,3S)

(2R,3S)-Ethyl 2,3-(isopropylidenedioxy)tridecanoateC18H34O4[α]D25=-14.6 (c 0.6, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (2R,3S)

(2R,3S)-Ethyl 2,3-(isopropylidenedioxy)pentadecanoateC20H38O4[α]D25=-10.8 (c 0.74, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (2R,3S)

(4S,5S,Z)-Ethyl 4,5-(isopropylidenedioxy)pentadec-2-enoateC20H36O4[α]D25=+37.1 (c 0.6, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4S,5S)

(4S,5S,Z)-Ethyl 4,5-(isopropylidenedioxy)heptadec-2-enoateC22H40O4[α]D25=+32.6 (c 0.4, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4S,5S)

(4S,5S,Z)-4,5-(Isopropylidenedioxy)pentadec-2-en-1-olC18H34O3[α]D25=+2.1 (c 0.54, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4S,5S)

(4S,5S,Z)-4,5-(Isopropylidenedioxy)heptadec-2-en-1-olC20H38O3[α]D25=+2.9 (c 0.6, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4S,5S)

(4R,5S)-5-[(S)-1-Hydroxyundecyl]-4-vinyl-4,5-dihydrofuran-2(3H)-oneC17H30O3[α]D25=+37.0 (c 0.32, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5S,1S)

(4S,5S)-5-[(S)-1-Hydroxyundecyl]-4-vinyl-4,5-dihydrofuran-2(3H)-oneC17H30O3[α]D25=+40.1 (c 0.28, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4S,5S,1S)

(4R,5S)-5-[(S)-1-Hydroxytridecyl]-4-vinyl-4,5-dihydrofuran-2(3H)-oneC19H34O3[α]D25=+37.6 (c 0.22, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5S,1S)

(4S,5S)-5-[(S)-1-Hydroxytridecyl]-4-vinyl-4,5-dihydrofuran-2(3H)-oneC19H34O3[α]D25=+34.2 (c 0.38, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4S,5S,1S)

(2R,3S)-4-Methylene-5-oxo-2-undecyltetrahydrofuran-3-carboxylic acid/(+)-nephrosterinic acidC17H28O4[α]D25=+12.5 (c 0.1, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (2R,3S)

(2R,3S)-4-Methylene-5-oxo-2-tridecyltetrahydrofuran-3-carboxylic acid/(+)-protolichesterinic acidC19H32O4[α]D25=+13.9 (c 0.16, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (2R,3S)