Total synthesis of the phytotoxic stagonolides A and B

The chemo-enzymatic and covergent synthesis of stagonolide B and the synthesis of stagonolide A, a phytotoxic 10-membered lactone have been achieved starting from d-ribose with overall yields of 25% and 8.7%, respectively. The synthesis contained simple steps in developing three centers’ key intermediates, namely the enzymatic (Novozyme-435) resolution of a propargylic alcohol followed by macrolactonization and RCM.

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Methyl 2,3-O-(1-methylethylidene)-β-d-ribofuranosideC9H16O5[α]D = −94 (c 0.1, CHCl3)Source of chirality: d-riboseAbsolute configuration: (2R,3S,4R)

Methyl 5-deoxy-5-iodo-2,3-O-(1-methylethylidene)-β-d-ribofuranosideC9H15O4I[α]D = −68.3 (c 0.1, CHCl3)Source of chirality: d-riboseAbsolute configuration: (2R,3S,4S)

(R)-1-((4R,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)butan-1-olC11H20O3[α]D = +4.5 (c 0.012, CHCl3)Source of chirality: d-riboseAbsolute configuration: (2R,3S,4R)

(R)-6-(Benzyloxy)-hex-1-yn-3-olC13H16O2[α]D = +10.4 (c 0.1, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(R)-6-(Benzyloxy)-hex-1-en-3-olC13H18O2[α]D = +18.3 (c 0.005, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

1-((4-(Methoxymethoxy) hex-5-enyloxy)methyl) benzeneC15H22O3[α]D = +53.65 (c 0.01, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4R)

4-(Methoxymethoxy) hex-5-en-1-olC8H16O3[α]D = +29.5 (c 0.01, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4R)

4-(Methoxymethoxy) hex-5-enoic acidC8H14O4[α]D = +17.75 (c 0.02, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4R)

(4R)-(R)-1-((4R,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl) butyl 4-(methoxymethoxy)hex-5-enoateC19H32O6[α]D = +26.1 (c 0.02, CHCl3)Source of chirality: d-ribose, enzymatic resolutionAbsolute configuration: (4R,5R,6S,4′R)

(E,5R,8S,9S,10R)-4,5,9,10-Tetrahydro-5,8,9-trihydroxy-10-propyl-3H-oxecin-2(8H)-oneC12H20O5[α]D = +24.5 (c 0.1, CHCl3)Source of chirality: d-ribose, enzymatic resolutionAbsolute configuration: (4R,8S,9S,10R)

(R)-1-((4R,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)butyl hex-5-enoateC17H28O4[α]D = +28.2 (c 0.1, CHCl3)Source of chirality: d-ribose, enzymatic resolutionAbsolute configuration: (1R,2S,3S)

(E,8S,9S,10R)-4,5,9,10-Tetrahydro-8,9-dihydroxy-10-propyl-3H-oxecin-2(8H)-oneC12H20O4[α]D = +12.8 (c 0.1, EtOH)Source of chirality: d-ribose, enzymatic resolutionAbsolute configuration: (8S,9S,10R,E)

(E,9R,10R)-4,5-9,10-Tetrahydro-9-hydroxy-10-propyl-3H-oxecin-2,8-dioneC12H18O4[α]D = −41.2 (c 0.01, EtOH)Source of chirality: d-ribose, enzymatic resolutionAbsolute configuration: (9R,10R)