Stereoselective total synthesis of polyketide lactone, (3R,4S,5S,9S)-3,5,9-trihydroxy-4-methylundecanoic acid δ-lactone

The total synthesis of lactone 1 has been described. The convergent asymmetric synthesis relies on the use of an Evans’ syn-aldol, chain extension with lithio tert-butyl acetate, and the stereoselective reduction of a ketone as the key reactions.

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(5S)-7-(Tetrahydro-2H-2-pyranyloxy)-3-heptyne-1,5-diolC12H20O4[α]D25=+5.1 (c 1.05, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (5S)

(3S)-7-(Benzyloxy)-1-(tetrahydro-2H-2-pyranyloxy)-4-heptyn-3-olC19H26O4[α]D25=-40.3 (c 0.9, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3S)

2-[(3S)-7-(Benzyloxy)-3-(methoxymethoxy)-4-heptynyl]oxytetrahydro-2H-pyranC21H30O5[α]D25=-36.9 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3S)

(3S)-7-(Benzyloxy)-3-(methoxymethoxy)-4-heptyn-1-olC16H22O4[α]D25=-88.1 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3S)

(3S)-7-(Benzyloxy)-3-(methoxymethoxy)-4-heptynyl 4-methyl-1-benzenesulfonateC23H28O6S[α]D25=-47.4 (c 1.35, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3S)

(5S)-1-(Benzyloxy)-5-(methoxymethoxy)-3-heptyneC16H22O3[α]D25=-99.3 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (5S)

(3R)-7-(Benzyloxy)-1-hepten-3-olC14H20O2[α]D25=-6.0 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3S)

(3R)-7-(Benzyloxy)-3-(methoxymethoxy)-1-hepteneC16H24O3[α]D25=+26.0 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(5S)-5-(Methoxymethoxy)heptan-1-olC9H20O3[α]D25=+4.9 (c 1.1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (5S)

(4R)-4-Benzyl-3-[(2R,3S,7S)-3-hydroxy-7-(methoxymethoxy)-2-methylnonanoyl]-1,3-oxazolan-2-oneC22H33NO6[α]D25=-38.4 (c 1.4, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4R,2R,3S,7S)

Methyl (2R,3S,7S)-3-hydroxy-7-(methoxymethoxy)-2-methylnonanoateC13H26O5[α]D25=-10.2 (c 1.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3S,7S)

tert-Butyl(4R,5S,9S)-5-hydroxy-9-(methoxymethoxy)-4-methyl-3-oxoundecanoateC18H34O6[α]D25=-5.0 (c 1.1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4R,5S,9S)

tert-Butyl(3R,4R,5S,9S)-3,5-dihydroxy-9-(methoxymethoxy)-4-methylundecanoateC18H36O6[α]D25=+3.0 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,4R,5S,9S)

(4R,5S,6S)-4-Hydroxy-6-[(4S)-4-hydroxyhexyl]-5-methyltetrahydro-2H-2-pyranoneC12H22O4[α]D25=-39.5 (c 0.27, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4R,5S,6S)