Synthesis of the C10–C24 fragment of (+)-cannabisativine

The stereoselective synthesis of the C10–C24 fragment of (+)-cannabisativine has been achieved. The key steps involved in this strategy are the Sharpless asymmetric dihydroxylation, the diastereoselective allylation of an imine, and the ring closing metathesis (RCM).

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(S,Z)-tert-Butyl 4-(hept-1-enyl)-2,2-dimethyloxazolidine-3-carboxylateC17H31NO3[α]D25=-75.5 (c 1.0, CHCl3)Source of chirality: d-serineAbsolute configuration: (2S,Z)

(S,Z)-tert-Butyl 1-hydroxynon-3-en-2-ylcarbamateC14H27NO3[α]D25=-27.2 (c 1.0, CHCl3)Source of chirality: d-serineAbsolute configuration: (2S,Z)

(S,Z)-2-(tert-Butoxycarbonylamino)non-3-enyl pivalateC19H35NO4[α]D25=-8.4 (c 0.7, CHCl3)Source of chirality: d-serineAbsolute configuration: (2S,Z)

(2R,3R,4S)-2-(tert-Butoxycarbonylamino)-3,4-dihydroxynonyl pivalateC19H37NO6[α]D25=-19.2 (c 1.35, CHCl3)Source of chirality: AD mix-αAbsolute configuration: (2R,3R,4S)

(2R,3R,4S)-2-(tert-Butoxycarbonylamino)-3,4-bis(methoxymethoxy)nonyl pivalateC23H45NO8[α]D25=+24.1 (c 1.0, CHCl3)Source of chirality: AD mix-αAbsolute configuration: (2R,3R,4S)

tert-Butyl (2R,3R,4S)-1-hydroxy-3,4-bis(methoxymethoxy)nonan-2-ylcarbamateC18H37NO7[α]D25=+30.3 (c 1.0, CHCl3)Source of chirality: AD mix-αAbsolute configuration: (2R,3R,4S)

tert-Butyl (3R,4R,5S,E)-4,5-bis(methoxymethoxy)-1-phenyldec-1-en-3-ylcarbamateC25H41NO6[α]D25=-18.5 (c 1.3, CHCl3)Source of chirality: AD mix-αAbsolute configuration: (3R,4R,5S,E)

(3R,4R,5S,E)-3-Amino-1-phenyldec-1-ene-4,5-diolC16H25NO2[α]D25=+14.0 (c 0.9, CHCl3)Source of chirality: AD mix-αAbsolute configuration: (3R,4R,5S,E)

(3R,4R,5S,E)-3-((R)-1-(4-Methoxybenzyloxy)hex-5-en-3-ylamino)-1-phenyldec-1-ene-4,5-diolC30H43NO4[α]D25=-5.5 (c 1.5, CHCl3)Source of chirality: diastereoselective allylationAbsolute configuration: (3R,4R,5S,E)

(4R,5R)-5-((S)-1-Hydroxyhexyl)-3-((R)-1-(4-methoxybenzyloxy)hex-5-en-3-yl)-4-((E)-styryl)oxazolidin-2-oneC31H41NO5[α]D25=+14.8 (c 1.0, CHCl3)Source of chirality: diastereoselective allylationAbsolute configuration: (4R,5R,3R,E)

(1R,5R,8aR)-1-((S)-1-Hydroxyhexyl)-5-(2-(4-methoxybenzyloxy)ethyl)-5,6-dihydro-1H-oxazolo[3,4-a]pyridin-3(8aH)-oneC23H33NO5[α]D25=+32.1 (c 1.1, CHCl3)Source of chirality: diastereoselective allylationAbsolute configuration: (1R,5R,8aR)