The stereoselective total synthesis of (−)-achaetolide

The stereoselective total synthesis of (−)-achaetolide is described in a convergent manner. Grignard addition, Wittig homologation, acetate aldol and ring closing metathesis reactions were the key steps involved. The required olefinic alcohol fragments were synthesized from a single chiral pool material 2-deoxy-d-ribose and olefinic acid fragment was prepared from acetate aldol reaction. Both the olefinic acid and alcohols were prepared in a concise method.

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(S)-1-[(4S,5R)-5-(Hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]nonan-2-olC15H30O4[α]D29=+8.1 (c 0.45, CHCl3)Source of chirality: 2-deoxy-d-riboseAbsolute configuration: (2R,3S,5S)

(R)-1-[(4S,5R)-5-(Hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]nonan-2-olC15H30O4[α]D29=+2.5 (c 0.15, CHCl3)Source of chirality: 2-deoxy-d-riboseAbsolute configuration: (2R,3S,5R)

(3aS,6S,7aS)-6-Heptyl-2,2-dimethyldihydro-3aH-[1,3]dioxolo[4,5-c]pyran-4(6H)-oneC15H26O4[α]D29=-35 (c 0.25, CHCl3)Source of chirality: 2-deoxy-d-riboseAbsolute configuration: (2R,3S,5S)

(3aS,6R,7aS)-6-Heptyl-2,2-dimethyldihydro-3aH-[1,3]dioxolo[4,5-c]pyran-4(6H)-oneC15H26O4[α]D29=+60 (c 0.3, CHCl3)Source of chirality: 2-deoxy-d-riboseAbsolute configuration: (2R,3S,5R)

(3aS,6S,7aS)-6-Heptyl-2,2-dimethyltetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-4-olC25H28O4[α]D29=+43.2 (c 0.55, CHCl3)Source of chirality: 2-deoxy-d-riboseAbsolute configuration: (2R,3S,5S)

(3aS,6R,7aS)-6-Heptyl-2,2-dimethyltetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-4-olC25H28O4[α]D29=+3.1 (c 1.0, CHCl3)Source of chirality: 2-deoxy-d-riboseAbsolute configuration: (2R,3S,5R)

(S)-1-[(4S,5R)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl]nonan-2-olC16H30O3[α]D27=-15.2 (c 0.6, CHCl3)Source of chirality: 2-deoxy-d-riboseAbsolute configuration: (3R,4S,6S)

(R)-1-[(4S,5R)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl]nonan-2-olC16H30O3[α]D27=-4.2 (c 1.3, MeOH)Source of chirality: 2-deoxy-d-riboseAbsolute configuration: (3R,4S,6R)

(S)-1-[(R)-4-Benzyl-2-thioxothiazolidin-3-yl]-3-hydroxypent-4-en-1-oneC15H17NO2S2[α]D27=-138.2 (c 1.3, CHCl3)Source of chirality: acetate aldolAbsolute configuration: (S,R)

(S)-1-[(R)-4-Benzyl-2-thioxothiazolidin-3-yl]-3-(tert-butyldimethylsilyloxy)pent-4-en-1-oneC21H31NO2S2Si[α]D27=+177.5 (c 1.5, CHCl3)Source of chirality: acetate aldolAbsolute configuration: (S,R)

(S)-3-(tert-Butyldimethylsilyloxy)pent-4-enoic acidC11H22O3Si[α]D27=-5.2 (c 0.7, MeOH)Source of chirality: acetate aldolAbsolute configuration: (3S)

(S)-{(R)-1-[(4S,5R)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl]nonan-2-yl) 3-(tert-butyldimethylsilyloxy)pent-4-enoateC11H22O3Si[α]D30=-7.3 (c 0.57, MeOH)Source of chirality: 2-deoxy-d-ribose, acetate aldolAbsolute configuration: (3S,6S,7R,9R)

(S)-{(R)-1-[(4S,5R)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl]nonan-2-yl} 3-hydroxypent-4-enoateC21H36O5[α]D28=-17.2 (c 0.7, CHCl3)Source of chirality: 2-deoxy-d-ribose, acetate aldolAbsolute configuration: (3S,6S,7R,9R)

(3aS,5R,9S,11aR,E)-5-Heptyl-9-hydroxy-2,2-dimethyl-4,5,8,9-tetrahydro-3aH-[1,3]dioxolo[4,5-d]oxecin-7(11aH)-oneC19H32O5[α]D29=-31.0 (c 0.8, CHCl3)Source of chirality: 2-deoxy-d-ribose, acetate aldolAbsolute configuration: (3S,6S,7R,9R)

AchaetolideC16H28O5[α]D28=-28.0 (c 0.4, MeOH)Source of chirality: 2-deoxy-d-ribose, acetate aldolAbsolute configuration: (3S,6S,7R,9R)