A concise synthesis of paraconic acids: (−)-methylenolactocin and (−)-phaseolinic acid

A concise synthesis of (−)-methylenolactocin and (−)-phaseolinic acid, the common members of the paraconic acids, is described. The synthesis is based on regioselective asymmetric dihydroxylation and the orthoester Johnson–Claisen rearrangement of allyl alcohol with a vicinal diol functionality as the key steps. The synthesis was completed in 10 steps with overall yields of 4.1% for (−)-methylenolactocin and 4.3% for (−)-phaseolinic acid.

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(4R,5R,2E)-Ethyl 4,5-dihydroxynon-2-enoateC11H20O4[α]D25=+38.2 (c 0.22, CHCl3)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5R,2E)

(4R,5R,2E)-Ethyl 4,5-isopropylidenedioxynon-2-enoateC14H24O4[α]D25=+6.2 (c 0.22, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5R,E)

(4R,5R,2E)-4,5-(Isopropylidenedioxy)nona-2-ene-1-olC12H22O3[α]D25=+22.8 (c 0.22, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5R,E)

(4S,5R)-5-[(R)-1-Hydroxypentyl]-4-vinyl-4,5-dihydrofuran-2(3H)-oneC11H18O3[α]D25=-48.9 (c 0.12, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4S,5R,1′R)

(4R,5R)-5-[(R)-1-hydroxypentyl]-4-vinyl-4,5-dihydrofuran-2(3H)-oneC11H18O3[α]D25=-50.5 (c 0.8, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5R,1′R)

S-Methyl O-(R)-1-[(2R,3S)-5-oxo-3-vinyltetrahydrofuran-2-yl]pentyl carbonodithioateC13H20O3S2[α]D25=+58.2 (c 0.14, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (2R,3S,1′R)

S-Methyl O-(R)-1-[(2R,3R)-5-oxo-3-vinyltetrahydrofuran-2-yl]pentyl carbonodithioateC13H20O3S2[α]D25=-34.7 (c 0.12, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (2R,3R,1′R)

(4S,5S)-5-Pentyl-4-vinyl-4,5-dihydrofuran-2(3H)-oneC11H18O2[α]D25=-79.6 (c 0.4, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4S,5S)

(4R,5S)-5-Pentyl-4-vinyl-4,5-dihydrofuran-2(3H)-oneC11H18O2[α]D25=-35.6 (c 0.24, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5S)

(2S,3R)-5-Oxo-2-pentyltetrahydrofuran-3-carboxylic acidC10H16O4[α]D25=-39.6 (c 0.16, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (2S,3R)

(2S,3S)-5-Oxo-2-pentyltetrahydrofuran-3-carboxylic acidC10H16O4[α]D25=-44.1 (c 0.16, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (2S,3S)

(2S,3R)-4-Methylene-5-oxo-2-pentyltetrahydrofuran-3-carboxylic acid / (−)-methylenolactocinC11H16O4[α]D25=-7.0 (c 0.12, CH3OH)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (2S,3R)

(2S,3S,4S)-4-Methyl-5-oxo-2-pentyltetrahydrofuran-3-carboxylic acid/(–)-phaseolinic acidC11H18O4[α]D25=-117 (c 0.10, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (2S,3S,4S)