A convenient chiron approach to (4R,5R)-5-hydroxyalkylbutan-4-olides and the corresponding 7-oxa analogues from d-(+)-mannitol via an advanced common precursor: syntheses of (−)-muricatacin, 7-oxa-(−)-muricatacin, (4R,5R)-(−)-5-hydroxy-4-decanolide, and (

An efficient and concise chiron approach toward the synthesis of (−)-muricatacin and its unnatural 7-oxa analogue starting from commercially available and inexpensive d-(+)-mannitol via an advanced common chiral precursor has been described. In addition, (4R,5R)-(−)-5-hydroxy-4-decanolide and (4R,5R)-(−)-7-oxa-5-hydroxy-4-dodecanolide were also synthesized to show the versatility of this synthetic strategy. The methodology involves the conversion of a common chiral intermediate, prepared from d-(+)-mannitol in six steps, to a variety of target molecules in only two steps.

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(E)-Ethyl 3-((4R,5S)-5-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)2,2-dimethyl-1,3-dioxolan-4-yl)acrylateC15H24O6Ee = 100%[α]D25 = −2.95 (c 0.60, CHCl3)Source of chirality: d-(+)-MannitolAbsolute configuration: (4R,5S)(R)

(E)-Ethyl 3-((4R,5R)-5-((R)-1,2-dihydroxyethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)acrylateC12H20O6Ee = 100%[α]D25 = +4.65 (c 0.50, CHCl3)Source of chirality: d-(+)-MannitolAbsolute configuration: (4R,5R)(R)

Ethyl 3-((4R,5R)-5-((R)-1,2-dihydroxyethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)propanoateC12H22O6Ee = 100%[α]D25 = +16.4 (c 3.72, CHCl3)Source of chirality: d-(+)-MannitolAbsolute configuration: (4R,5R)(R)

Ethyl 3-((4R,5R)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)propanoateC11H20O5Ee = 100%[α]D25 = +24.9 (c 0.60, CHCl3)Source of chirality: d-(+)-MannitolAbsolute configuration: (4R,5R)

(4R,5R)-(−)-MuricatacinC17H32O3Ee = 100%[α]D25 = −21.8 (c 1.06, CHCl3)Source of chirality: d-(+)-MannitolAbsolute configuration: (4R,5R)

(4R,5R)-(−)-5-Hydroxy-4-decanolideC10H18O3Ee = 100%[α]D25 = −32.4 (c 0.33, CHCl3)Source of chirality: d-(+)-MannitolAbsolute configuration: (4R,5R)

(4R,5R)-7-Oxa-(−)-muricatacinC16H30O4Ee = 100%[α]D25 = −32.5 (c 0.80, CHCl3)Source of chirality: d-(+)-MannitolAbsolute configuration: (4R,5R)

(4R,5R)-(−)-7-Oxa-5-hydroxy-4-dodecanolideC11H20O4Ee = 100%[α]D25 = −29.5 (c 0.30, CHCl3)Source of chirality: d-(+)-MannitolAbsolute configuration: (4R,5R)