Total synthesis of (+)-synargentolide A

The highly stereoselective total synthesis of polyacetate α,β-unsaturated δ-lactone natural product (+)-synargentolide A has been accomplished from inexpensive d-1,5-gluconolactone. Key reactions involved in the synthesis are hydroboration, Wittig olefination, Brown’s asymmetric allylation, and a ring closing metathesis reaction.

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(4S,41R,5R)-2,2,21,21-Tetramethyl-5-vinyl-4,41-bi(1,3-dioxolan)C12H20O4[α]D25=-5.75 (c 3.0, CHCl3)Source of chirality: sugarAbsolute configuration: (4S,41R,5R)

2-(4S,41R,5R)-2,2,21,21-Tetramethyl-4,41-bi(1,3-dioxolan)-5-yl)ethanolC12H22O5[α]D25=+15.5 (c 0.8, CHCl3)Source of chirality: sugarAbsolute configuration: (4S,41R,5R)

(4S,41R,5R)-5-(2-(Benzyloxy)ethyl)-2,2,21,21-tetra-methyl-4,41-bi(1,3-dioxolane)C19H28O5[α]D25=+17.6 (c 1.0, CHCl3).Source of chirality: sugarAbsolute configuration: (4S,41R,5R)

(R)-1-((4R,5R)-5-(2-(Benzyloxy)ethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)ethane-1,2-diolC16H24O5[α]D25=+8.7 (c 2.8, CHCl3).Source of chirality: sugarAbsolute configuration: (R)-1-((4R,5R)

(R)-1-((4R,5R)-5-(2-(Benzyloxy)ethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)ethanolC13H24O4[α]D25=+20.5 (c 0.8, CHCl3).Source of chirality: sugarAbsolute configuration: (R)-1-((4R,5R)

((R)-1-((4S,5R)-5-(2-(Benzyloxy)ethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)ethoxy)(tert-butyl)dimethylsilaneC22H38O4Si[α]D25=+11.7 (c 1.5, CHCl3)Source of chirality: sugarAbsolute configuration: (R)-1-((4S,5R)

2-((4R,5S)-5-((R)-1-(tert-Butyldimethylsilyloxy)ethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)ethanolC15H32O4Si[α]D25=-5.8 (c 1.1, CHCl3)Source of chirality: sugarAbsolute configuration: 2-((4R,5S)-5-((R)

(E)-Ethyl 4-((4R,5S)-5-((R)-1-(tert- Butyldimethylsilyloxy)ethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)but-2-enolateC19H36O5Si[α]D25=+22.6 (c 2.3, CHCl3)Source of chirality: sugarAbsolute configuration: (E)-Ethyl 4-((4R,5S)-5-((R)

(E)-4-((4R,5S)-5-((R)-1-(tert-Butyldimethylsilyloxy) ethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)but-2-en-1-olC17H34O4Si[α]D25=+8.9 (c 2.7, CHCl3)Source of chirality: sugarAbsolute configuration: (E)-4-((4R,5S)-5-((R)

(R,E)-7-((4R,5S)-5-((R)-1-(tert-Butyldimethylsilyloxy)ethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)hepta-1,5-dien-4-olC20H38O4Si[α]D25=+15.8 (c 1.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,E)-7-((4R,5S)-5-((R)

(R,E)-7-((4R,5S)-5-((R)-1-(tert-Butyldimethylsilyloxy)ethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)hepta-1,5-dien-4-yl acrylateC23H40O5Si[α]D25=+18.7 (c 2.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,E)-7-((4R,5S)-5-((R)

(R)-6-((E)-3-((4R,5S)-5-((R)-1-(tert-Butyldimethylsilyloxy)ethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)prop-1-enyl)-5,6-dihydro-2H-pyran-2-oneC21H36O5Si[α]D25=+31.8 (c 1.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)-6-((E)-3-((4R,5S)-5-((R)

(2R,3R,4R,E)-7-((R)-6-Oxo-3,6-dihydro-2H-pyran-2-yl)heap-6-ene-2,3,4-triacetateC18H24O8[α]D25=+52 (c 0.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4R,E)-7-((R)