Towards the total synthesis of etnangien: synthesis of C32–C42 fragment by using a desymmetrization strategy

The construction of the C32–C42 fragment of etnangien is described using a desymmetrization strategy generating five stereogenic centers from a bicyclic lactone. Another notable feature includes the use of the Sharpless asymmetric epoxidation to generate a stereogenic center at C40.

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(4R)-7-(Benzyloxy)-4-allyl-6,8-dimethyl-2,9-dioxabicyclo[3.3.1]nonan-3-oneC19H24O4[α]D25=-34.6 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4R)

(2R,3R,4S,5R,6R)-2-Allyl-5-(benzyloxy)-4,6 dimethylheptane-1,3,7-triolC19H30O4[α]D25=+1.3 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4S,5R,6R)

(2R,3R,4R)-4-[(4R,5R)-5-Allyl-2,2-dimethyl-1,3-dioxan-4-yl]-3-(benzyloxy)-2-methylpentan-1-olC22H34O4[α]D25=-19.9 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4R)

(2R,3R,4R)-4-[(4R,5R)-5-Allyl-2,2-dimethyl-1,3-dioxan-4-yl]-3-(benzyloxy)-2-methylpentyl pivalateC27H42O5[α]D25=-18.4 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4R,5R)

(2R,3R,4S,5R,6R)-3-(Benzyloxy)-5-hydroxy-6-(hydroxymethyl)-2,4-dimethyl-8-nonenyl pivalateC27H42O5[α]D25=+9.8 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4S,5R,6R)

(2R,3R,4R,5R,6R)-3-(Benzyloxy)-5-[1-(tert-butyl)-1,1-dimethylsilyl]oxy-2,4-dimethyl-6-([(4-methylphenyl)sulfonyl]oxymethyl)-8-nonenyl pivalateC31H44O7S[α]D25=+10.9 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4R,5R,6R)

(2R,3R,4R,5R,6S)-3-(Benzyloxy)-5-[1-(tert-butyl)-1,1-dimethylsilyl]oxy-2,4,6-trimethyl-8-nonen-1-olC37H58O7SSi[α]D25=+3.7 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4R,5R,6S)

(2R,3R,4R,5R,6S)-3-(Benzyloxy)-5-[1-(tert-butyl)-1,1-dimethylsilyl]oxy-2,4,6-trimethyl-8-nonen-1-olC25H44O3Si[α]D25=-25.3 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4R,5R,6S)

Ethyl (2E,4R,5R,6R,7R,8S)-5-(benzyloxy)-7-[1-(tert-butyl)-1,1-dimethylsilyl]oxy-4,6,8-trimethyl-2,10-undecadienoateC29H48O4Si[α]D25=-7.5 (c 1.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2E,4R,5R,6R,7R,8S)

(2E,4R,5R,6R,7R,8S)-5-(Benzyloxy)-7-[1-(tert-butyl)-1,1-dimethylsilyl]oxy-4,6,8-trimethyl-2,10-undecadien-1-olC27H46O3Si[α]D25=+1.4 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2E,4R,5R,6R,7R,8S)

[(2S,3S)-3-((1S,2R,3R,4R,5S)-2-(Benzyloxy)-4-[1-(tert-butyl)-1,1-dimethylsilyl]oxy-1,3,5-trimethyl-7-octenyl)oxiran-2-yl]methanolC27H46O4Si[α]D25=-12.8 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: [(2S,3S)-3-((1S,2R,3R,4R,5S))]

(3R,4R,5R,6R,7R,8S)-5-(Benzyloxy)-7-[1-(tert-butyl)-1,1-dimethylsilyl]oxy-4,6,8-trimethyl-10-undecene-1,3-diolC27H48O4Si[α]D25=+1.6 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,4R,5R,6R,7R,8S)

(3R,4R,5R,6R,7R,8S)-7-[1-(tert-Butyl)-1,1-dimethylsilyl]oxy-4,6,8-trimethyl-10-undecene-1,3,5-triolC20H42O4Si[α]D25=-14.6 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,4R,5R,6R,7R,8S)

(2S,3R,4R,5R,6S)-5-[1-(tert-Butyl)-1,1-dimethylsilyl]oxy-2-[(4R)-2-(4-methoxyphenyl)-1,3-dioxan-4-yl]-4,6-dimethyl-8-nonen-3-olC28H48O5Si[α]D25=-9.4 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R,4R,5R,6S)

(2S,3S,4R,5R,6S)-5-[1-(tert-Butyl)-1,1-dimethylsilyl]oxy-2-[(4R)-2-(4-methoxyphenyl)-1,3-dioxan-4-yl]-4,6-dimethyl-8-nonen-3-olC28H48O5Si[α]D25=-11.5 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S,4R,5R,6S)

tert-Butyl[((1R,2S)-1-(1R,2S,3S)-2-(methoxymethoxy)-3-[(4R)-2-(4-methoxyphenyl)-1,3-dioxan-4-yl]-1-methylbutyl-2-methyl-4-pentenyl)oxy]dimethylsilaneC18H36O6[α]D25=-3.3 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2S)-1-(1R,2S,3S)

(3R,4R,5S,6R,7R,8S)-7-[1-(tert-Butyl)-1,1-dimethylsilyl]oxy-3-[(4-methoxybenzyl)oxy]-5-(methoxymethoxy)-4,6,8-trimethyl-10-undecen-1-olC30H54O6Si[α]D25=+11.7 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,4R,5S,6R,7R,8S)