Total synthesis of (−)-lentiginosine

The total synthesis of (−)-lentignosine is achieved from d-glyceraldehyde in good yields involving a Sharpless asymmetric epoxidation and a one-pot indolizidine construction strategy.

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(2S)-2-{6-[(4-Methoxybenzyl)oxy]-1-hexynyl}-1,4-dioxaspiro[4.5]decaneC22H30O4[α]D25=+24.5 (c 1.2, CHCl3)Source of chirality: d-(+)-mannitolAbsolute configuration: (2S)

(2S)-8-[(4-Methoxybenzyl)oxy]-3-octyne-1,2-diolC16H22O4[α]D25=+11.0 (c 1.2, CHCl3)Source of chirality: d-(+)-mannitolAbsolute configuration: (2S)

(2S,3E)-8-[(4-Methoxybenzyl)oxy]-3-octene-1,2-diolC16H24O4[α]D25=+7.2 (c 1.0, CHCl3)Source of chirality: d-(+)-mannitolAbsolute configuration: (2S,3E)

(1R)-1-{(2S,3S)-3-4-[(4-Ethylbenzyl)oxy]butyloxiran-2-yl}ethane-1,2-diolC16H24O5[α]D25=-12.8 (c 1.0, CHCl3)Source of chirality: d-(+)-mannitol, (+)-diisoporpyl l-tartrateAbsolute configuration: (1R,2S,3S)

(R)-2-Azido-1-((2S,3S)-3-(4-(4-methoxybenzyloxy)butyl)oxiran-2-yl)ethanolC16H23N3O4[α]D25=-8.0 (c 0.5, CHCl3)Source of chirality: d-(+)-mannitol, (+)-diisoporpyl l-tartrateAbsolute configuration: (1R,2S,3S)

4-((2S,3S)-3-((R)-2-Azido-1-hydroxyethyl)oxiran-2-yl)butan-1-olC8H15N3O3[α]D25=-11.0 (c 0.25, CHCl3)Source of chirality: d-(+)-mannitol, (+)-diisoporpyl l-tartrateAbsolute configuration: (1R,2S,3S)

4-((2S,3S)-3-((R)-2-Azido-1-hydroxyethyl)oxiran-2-yl)butyl-4-methylbenzenesulfonateC15H21N3O5S[α]D25=+19.0 (c 1.0, CHCl3)Source of chirality: d-(+)-mannitol, (+)-diisoporpyl l-tartrateAbsolute configuration: (1R,2S,3S)

(1R,2R,8aR)-1,2-Dihydroxyindolizidine, [(−)-lentiginosine]C8H15NO2[α]D25=-3.1 (c 0.5 MeOH)Source of chirality: d-(+)-mannitol, (+)-diisoporpyl l-tartrateAbsolute configuration: (1R,2R,8aR)