Convenient approach to an advanced intermediate for salinosporamide A synthesis

An approach towards the advanced scaffold 21 as an intermediate for salinosporamide A 1 synthesis has been developed starting from the known ulose 3. This strategy involves the 2-hydroxyethyl moiety installation at the C-5 position via a Wittig transformation followed by Pd/C-mediated hydrogenation of the conformationally constrained alkene 9 in a stereoselective manner, and the Overman rearrangement, thus allowing full control over the configuration of the newly generated quaternary stereocentre with an amino group in 18.

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(Z)-Ethyl 3-O-(tert-butyldimethylsilyl)-5-C-[(tert-butyldimethylsilyloxy)methyl]-5,6-dideoxy-1,2-O-isopropylidene-β-l-lyxo-hept-5-enfuranuronateC25H48O7Si2[α]D25 = +166.3 (c 0.40, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3R,4S,5Z)

(5Z)-3-O-(tert-Butyldimethylsilyl)-5-C-[(tert-butyldimethylsilyloxy)methyl]-5,6-dideoxy-1,2-O-isopropylidene-β-l-lyxo-hept-5-enfuranoseC23H46O6Si2[α]D25 = +59.2 (c 0.24, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3R,4S,5Z)

(5Z)-7-O-Acetyl-3-O-(tert-butyldimethylsilyl)-5-C-[(tert-butyldimethylsilyloxy)methyl]-5,6-dideoxy-1,2-O-isopropylidene-β-l-lyxo-hept-5-enfuranoseC25H48O7Si2[α]D25 = +39.1 (c 0.44, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3R,4S,5Z)

(5Z)-7-O-Acetyl-5,6-dideoxy-5-C-(hydroxymethyl)-1,2-O-isopropylidene-β-l-lyxo-hept-5-enfuranoseC13H20O7[α]D25 = +39.2 (c 0.36, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3R,4S,5Z)

5-C-(Z)-[2′-(Acetyloxy)ethylidene]-5-deoxy-1,2:3,6-di-O-isopropylidene-β-l-lyxo-hexofuranoseC16H24O7[α]D25 = −140.8 (c 0.48, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3R,4S,5Z)

5-Deoxy-5-C-(Z)-(2′-hydroxyethylidene)-1,2:3,6-di-O-isopropylidene-β-l-lyxo-hexofuranoseC14H22O6[α]D25 = −112.2 (c 0.60, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3R,4S,5Z)

(5S)-5-Deoxy-5-C-(2′-hydroxyethyl)-1,2:3,6-di-O-isopropylidene-β-l-lyxo-hexofuranoseC14H24O6[α]D25 = −19.8 (c 0.48, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3R,4S,5S)

(5R)-5-Deoxy-5-C-(2′-hydroxyethyl)-1,2:3,6-di-O-isopropylidene-β-l-lyxo-hexofuranoseC14H24O6[α]D25 = −38.5 (c 0.46, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3R,4S,5R)

(5S)-7-O-Benzyl-5,6-dideoxy-5-C-(hydroxymethyl)-1,2-O-isopropylidene-β-l-lyxo-heptofuranoseC18H26O6[α]D25 = +7.6 (c 2.08, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3R,4S,5R)

(5S)-7-O-Benzyl-5-C-[(tert-butyldimethylsilyloxy)methyl]-5,6-dideoxy-1,2-O-isopropylidene-β-l-lyxo-heptofuranoseC24H40O6Si[α]D25 = +10.0 (c 0.56, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3R,4S,5R)

(5S)-7-O-Benzyl-5-C-[(tert-butyldimethylsilyloxy)methyl]-5,6-dideoxy-1,2-O-isopropylidene-β-l-threo-heptofuranos-3-uloseC24H38O6Si[α]D25 = −13.0 (c 0.60, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2S,4S,5S)

(5S)-7-O-Benzyl-5-C-[(tert-butyldimethylsilyloxy)methyl]-3,5,6-trideoxy-3-C-(E)-(2′-ethoxy-2′-oxoethylidene)-1,2-O-isopropylidene-β-l-threo-heptofuranoseC28H44O7Si[α]D25 = −8.3 (c 0.60, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3E,4S,5S)

(5R)-5-C-[2‴-(Benzyloxy)ethyl]-3-(2′,2′,2′-trichloroacetamido)-3,5-dideoxy-1,2-O-isopropylidene-3-C-vinyl-β-l-arabino-hexofuranuronic acidC22H26Cl3NO7[α]D25 = +6.55 (c 0.58, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3S,4S,5R)

(5S)-7-O-Benzyl-5-C-[(tert-butyldimethylsilyloxy)methyl]-3-(2′,2′,2′-trichloroacetamido)-3,5,6-trideoxy-1,2-O-isopropylidene-3-C-vinyl-β-l-arabino-heptofuranoseC28H42Cl3NO6Si[α]D25 = +7.2 (c 032, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3S,4S,5S)

(5S)-7-O-Benzyl-5-C-[(tert-butyldimethylsilyloxy)methyl]-3,5,6-trideoxy-3-C-(E)-(2′-hydroxyethylidene)-1,2-O-isopropylidene-β-l-threo-heptofuranoseC26H42O6Si[α]D25 = +6.0 (c 0.72, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3E,4S,5S)

(5S)-7-O-Benzyl-3-(2′,2′,2′-trichloroacetamido)-3,5,6-trideoxy-5-C-(hydroxymethyl)-1,2-O-isopropylidene-3-C-vinyl-β-l-arabino-heptofuranoseC22H28Cl3NO6[α]D25 = +10.4 (c 0.48, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3S,4S,5S)

Methyl (5R)-5-C-[2‴-(benzyloxy)ethyl]-3-(2′,2′,2′-trichloroacetamido)-3,5-dideoxy-1,2-O-isopropylidene-3-C-vinyl-β-l-arabino-hexofuranuronateC23H28Cl3NO7[α]D25 = +5.3 (c 1.10, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3S,4S,5S)