Stereoselective total synthesis of rubrenolide and rubrynolide

The stereoselective total synthesis of rubrenolide and rubrynolide has been accomplished successfully. The synthetic strategy involves Evans alkylation and asymmetric CBS reduction to establish the required stereogenic centers. Other key steps involve Horner–Wadsworth–Emmons (HWE) olefination to construct the side chain, alkynylation to introduce terminal unsaturation in the side chain, and TEMPO-BAIB-mediated lactonization.

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(R)-4-Benzyl-3-(3-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)propanoyl)oxazolidin-2-oneC18H23NO5[α]D25 = −33.7 (c 2.13, CHCl3)Source of chirality: l-Ascorbic acidAbsolute configuration: (4R,4′R)

(R)-4-Benzyl-3-((R)-2-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)pent-4-enoyl)oxazolidin-2-oneC21H27NO5[α]D25 = −32.4 (c 1.9, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (2R,4R,4′R)

(R)-2-(((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)pent-4-en-1-olC11H20O3[α]D25 = −6.4 (c 0.96, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (2R,4R)

tert-Butyl((R)-2-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)pent-4-enyloxy)diphenylsilaneC27H38O3Si[α]D25 = −1.4 (c 1.09, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (2R,4R)

Dimethyl (S)-5-(tert-butyldiphenylsilyloxy)-4-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-2-oxopentylphosphonateC29H43O7PSi[α]D25 = −2.8 (c 2.53, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (2R,4S)

(S,E)-13-(Benzyloxy)-1-(tert-butyldiphenylsilyloxy)-2-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)tridec-5-en-4-oneC42H58O5Si[α]D25 = −4.2 (c 1.37, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (2R,4S,7E)

(2R,4S,E)-13-(Benzyloxy)-1-(tert-butyldiphenylsilyloxy)-2-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)tridec-5-en-4-olC42H60O5Si[α]D25 = −2.7 (c 2.34, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (2R,4R,6S,7E)

(5S,7S)-5-((E)-9-(Benzyloxy)non-1-enyl)-7-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-2,2,3,3,11,11-hexamethyl-10,10-diphenyl-4,9-dioxa-3,10-disiladodecaneC48H74O5Si2[α]D25 = −1.6 (c 1.54, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (2R,4S,6S,7E)

(10R,12S)-10-(tert-Butyldimethylsilyloxy)-13-(tert-butyldiphenylsilyloxy)-12-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)tridecan-1-olC41H70O5Si2[α]D25 = −2.5 (c 0.74, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (2R,4S,6S)

(5R,7S)-5-(Dec-9-ynyl)-7-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-2,2,3,3,11,11-hexamethyl-10,10-diphenyl-4,9-dioxa-3,10-disiladodecaneC42H68O4Si2[α]D25 = −2.0 (c 1.26, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (2R,4S,6R)

(2R,4R)-2-(((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)tetradec-13-yne-1,4-diolC20H36O4[α]D25 = −3.6 (c 1.04, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (2R,4R,6R)

(3R,5R)-5-(Dec-9-ynyl)-3-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)dihydrofuran-2(3H)-oneC20H32O4[α]D25 = +14.6 (c 0.31, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (2R,4R,2′R)

(3S,5R)-5-(Dec-9-ynyl)-3-((R)-2,3-dihydroxypropyl)dihydrofuran-2(3H)-oneC17H28O4[α]D25 = +20.6 (c 0.31, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (2S,4R,2′R)

(3S,5R)-5-(Dec-9-enyl)-3-((R)-2,3-dihydroxypropyl)dihydrofuran-2(3H)-oneC17H30O4[α]D25 = +20.8 (c 0.53, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (2S,4R,2′R)