First stereoselective total synthesis of (−)-stagonolide A

The first stereoselective total synthesis of the nonenolide (−)-stagonolide A is described. Olefin metathesis and epoxide opening reaction are the key steps involved.

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(2R,3R)-(3-Propyl-oxiranyl)-methanolC6H12O2[α]D27=+40.5 (c 1.0, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (2R,3R)

(2S,3R)-2-(Chloromethyl)-3-propyloxiraneC6H11OCl[α]D27=+10.0 (c 2.8, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (2S,3R)

(3R)-Hex-1-yn-3-olC6H10O[α]D27=+15.8 (c 0.3, CHCl3)Source of chirality: epoxide openingAbsolute configuration: (3R)

(3R)-3-tert-Butyldimethylsilyloxy-hex-1-yneC12H24OSi[α]D29=+27.9 (c 1.2, CHCl3)Source of chirality: epoxide openingAbsolute configuration: (3R)

(4R)-(tert-Butyl-dimethyl-silanyloxy)-hept-2-ynoicacid ethyl esterC15H28O3Si[α]D30=+8.0 (c 1.0, CHCl3)Source of chirality: epoxide openingAbsolute configuration: (4R)

(4R)-(tert-Butyl-dimethyl-silanyloxy)-hept-2-enoic acid ethylesterC15H30O3Si[α]D30=-14.8 (c 1.9, CHCl3)Source of chirality: epoxide openingAbsolute configuration: (4R)

(2R,3S,4R)-4-(tert-Butyldimethylsilyloxy)-2,3-dihydroxy-heptanoicacid ethylesterC15H32O5Si[α]D30=-4.5 (c 1.2, CHCl3)Source of chirality: dihydroxylationAbsolute configuration: (2R,3S,4R)

(2R,3S,4R)-5-[1-(tert-Butyl-dimethyl-silanyloxy)-butyl]-2,2dimethyl-[1,3]dioxolane-4-carboxylic acid ethyl esterC18H36O5Si[α]D30=+25.8 (c 1.2, CHCl3)Source of chirality: epoxide opening, dihydroxylationAbsolute configuration: (2R,3S,4R)

(2S,3S,4R)-5-[1-(tert-Butyl-dimethyl-silanyloxy]-2,2-dimethyl-[1,3]dioxolan-4-yl-methanolC16H34O4Si[α]D28=+39.1 (c 1.0, CHCl3)Source of chirality: epoxide opening, dihydroxylationAbsolute configuration: (2S,3S,4R)

(2R,3S,4R)5-[1-(tert-Butyl-dimethyl-silanyloxy)-butyl]-2,2dimethyl-[1,3]dioxolane-4-carbaldehydeC16H32OSi[α]D30=-13.6 (c 1.1, CHCl3)Source of chirality: epoxide opening, dihydroxylationAbsolute configuration: (2R,3S,4R)

tert-(3S,4S,5R)Butyl-[-(2,2-dimethyl-5-vinyl-[1,3]dioxolan-4-yl-butoxyl-dimethyl-silaneC17H34O3Si[α]D27.4=-19.6 (c 1.1, CHCl3)Source of chirality: epoxide opening, dihydroxylationAbsolute configuration: (3S,4S,5R)

(R)-1-((4R,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)butan-1-olC11H20O3[α]D30=+8.8 (c 1.6, CH2Cl2)Source of chirality: epoxide opening, dihydroxylation, and d-riboseAbsolute configuration: (1R,4R,5S)

(R)-1-((4R,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)butyl hept-6-enoateC17H28O4[α]D30=+19.7 (c 1.5, CH2Cl2)Source of chirality: epoxide opening, dihydroxylation, and d-ribose.Absolute configuration: (1R,4S,5S)

Herbarumin-1C12H20O4[α]D31=+11.2 (c 0.7, EtOH)Source of chirality: epoxide opening, dihydroxylation, and d-ribose.Absolute configuration: (7S,8R,9S)

Stagonolide AC12H18O4[α]D32=-60 (c 0.2, EtOH)Source of chirality: epoxide opening, dihydroxylation, and d-ribose.Absolute configuration: (8R,9S)