Synthesis of two piperidine alkaloids, (−)-deoxoprosopinine and (−)-deoxoprosophylline, from 6-hydroxylated dihydrosphingosine derivatives

(−)-Deoxoprosopinine 1 [(2S,3R,6S)-6-dodecyl-2-hydroxymethylpiperidin-3-ol] and (−)-deoxoprosophylline 3 [(2S,3R,6R)-6-dodecyl-2-hydroxymethylpiperidin-3-ol] were synthesized from (6R)- and (6S)-6-mesyloxydihydrosphingosine derivatives 7 and 7′, respectively, by intramolecular cyclization to generate a piperidine ring.

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tert-Butyl (4S,1′R,4′R)-4-(1′,4′-dihydroxyhexadecyl)-2,2-dimethyl-3-oxazolidinecarboxylateC26H51NO5[α]D26=-16.8 (c 1.02, CHCl3)Source of chirality: (S)-serine and lipase-catalyzed asymmetric acetylationAbsolute configuration: (4S,1′R,4′R)

tert-Butyl (4S,1′R,4′S)-4-(1′,4′-dihydroxyhexadecyl)-2,2-dimethyl-3-oxazolidinecarboxylateC26H51NO5[α]D26=-15.1 (c 1.03, CHCl3)Source of chirality: (S)-serine and lipase-catalyzed asymmetric acetylationAbsolute configuration: (4S,1′R,4′S)

(2S,3R,6R)-2-tert-Butoxycarbamidoctadecane-1,3,6-triolC23H47NO5[α]D26=+3.3 (c 0.53, CHCl3)Source of chirality: (S)-serine and lipase-catalyzed asymmetric acetylationAbsolute configuration: (2S,3R,6R)

(2S,3R,6S)-2-tert-Butoxycarbamidoctadecane-1,3,6-triolC23H47NO5[α]D26=+5.8 (c 0.53, CHCl3)Source of chirality: (S)-serine and lipase-catalyzed asymmetric acetylationAbsolute configuration: (2S,3R,6S)

(2S,4R,5S,3′R)-5-tert-Butoxycarbamido-4-(3′-hydroxypentadecyl)-2-phenly-1,3-dioxacyclohexaneC30H51NO5[α]D26=+25.0 (c 0.54, CHCl3)Source of chirality: (S)-serine and lipase-catalyzed asymmetric acetylationAbsolute configuration: (2S,4R,5S,3′R)

(2S,4R,5S,3′S)-5-tert-Butoxycarbamido-4-(3′-hydroxypentadecyl)-2-phenly-1,3-dioxacyclohexaneC30H51NO5[α]D26=+19.7 (c 0.54, CHCl3)Source of chirality: (S)-serine and lipase-catalyzed asymmetric acetylationAbsolute configuration: (2S,4R,5S,3′S)

tert-Butyl (1S,2S,4R,6S)-6-dodecyl-2-phenylhexahydro[1,3]dioxino[5,4-b]pyridine-5-carboxylateC30H49NO4[α]D26=-24.3 (c 0.54, CHCl3)Source of chirality: (S)-serine and lipase-catalyzed asymmetric acetylationAbsolute configuration: (1S,2S,4R,6S)

tert-Butyl (1S,2S,4R,6R)-6-dodecyl-2-phenylhexahydro[1,3]dioxino[5,4-b]pyridine-5-carboxylateC30H49NO4[α]D26=-24.3 (c 0.54, CHCl3)Source of chirality: (S)-serine and lipase-catalyzed asymmetric acetylationAbsolute configuration: (1S,2S,4R,6R)

(−)-Deoxoprosopinine (2S,3R,6S)-6-dodecyl-2-hydroxymethylpiperidin-3-olC18H37NO2[α]D24=-14.3 (c 0.54, CHCl3)Source of chirality: (S)-serine and lipase-catalyzed asymmetric acetylationAbsolute configuration: (2S,3R,6S)

(−)-Deoxoprosophylline (2S,3R,6R)-6-dodecyl-2-hydroxymethylpiperidin-3-olC18H37NO2[α]D24=-14.2 (c 0.58, CHCl3)Source of chirality: (S)-serine and lipase-catalyzed asymmetric acetylationAbsolute configuration: (2S,3R,6R)