Total synthesis of (−)-lentiginosine

A simple and practical synthesis of (−)-lentiginosine 2 with good overall yield has been achieved from the commercially available diethyl d-tartarate. The key steps are a highly stereoselective Grignard reaction on an aldehyde and a Staudinger reduction.

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(2R,3R,4S)-1-(tert-Butyldiphenylsilyloxy)-2,3-bis(methoxymethoxy)oct-7-en-4-olC28H42O6Si[α]D25 = −11.3 (c 0.7, CHCl3)Source of chirality: Diethyl d-tartrateAbsolute configuration: (2R,3R,4S)

(2R,3R,4R)-1-(tert-Butyldiphenylsilyloxy)-2,3-bis(methoxymethoxy)oct-7-en-4-olC28H42O6Si[α]D25 = −4.4 (c 0.9, CHCl3)Source of chirality: Diethyl d-tartrateAbsolute configuration: (2R,3R,4R)

(5S,6R,7R)-8-(tert-Butyldiphenylsilyloxy)-6,7-bis(methoxymethoxy)octane-1,5-diolC28H44O7Si[α]D25 = −2.1 (c 0.9, CHCl3)Source of chirality: Diethyl d-tartrateAbsolute configuration: (5S,6R,7R)

(2R,3R,4S)-8-Azido-1-(tert-butyldiphenylsilyloxy)-2,3-bis(methoxymethoxy)octan-4-olC28H43N3O6Si[α]D25 = −6.5 (c 1.1, CHCl3)Source of chirality: Diethyl d-tartrateAbsolute configuration: (2R,3R,4S)

(2R,3R,4S)-8-Azido-2,3-bis(methoxymethoxy)octane-1,4-diolC12H25N3O6[α]D25 = +8.7 (c 1.2, CHCl3)Source of chirality: Diethyl d-tartrateAbsolute configuration: (2R,3R,4S)

(1R,2R,8aR)-1,2-Bis(methoxymethoxy)octahydroindolizineC12H23NO4[α]D25 = +27.7 (c 0.8, CHCl3)Source of chirality: Diethyl d-tartrateAbsolute configuration: (1R,2R,8aR)

(1R,2R,8aR)-Octahydroindolizine-1,2-diolC8H15NO2[α]D25 = −2.9 (c 0.5, MeOH)Source of chirality: Diethyl d-tartrateAbsolute configuration: (1R,2R,8aR)