Total synthesis of phytotoxic herbarumin-I from d-mannitol

A simple carbohydrate-based convergent approach towards the total synthesis of herbarumin-I, a 10-membered lactone is described. The key features of the synthetic strategy include Grignard reaction and ring-closing metathesis reaction for the formation of the 10-membered ring and E-olefinic moiety. d-Mannitol has been used as a chiral pool material for the construction of the key fragment.

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(4R,5R,6S)-5,6-Di(benzyloxy)-7-octen-4-olC22H28O3[α]D25=+62.1 (c 1.1, CHCl3)Source of chirality: d-mannitol and asymmetric synthesisAbsolute configuration: (4R,5R,6S)

[(1R,2S,3S)-2,3-Di(benzyloxy)-1-propyl-4-pentenyl]oxy-1,6-heptadieneC28H36O4[α]D25=+68.2 (c 1.1, CHCl3)Source of chirality: d-mannitol and asymmetric synthesisAbsolute configuration: (1R,2S,3S)

(8S,9S,10R)-8,9-Di(benzyloxy)-10-propyl-3,4,5,8,9,10-hexahydro-2H-2-oxecinoneC26H32O4[α]D25=+43.2 (c 1.0, CHCl3)Source of chirality: d-mannitol and asymmetric synthesisAbsolute configuration: (1R,2S,3S)

(8S,9S,10R)-8,9-Dihydroxy-10-propyl-3,4,5,8,9,10-hexahydro-2H-2-oxecinone (or) herbarumin-IC12H20O4[α]D25=+10.6 (c 1.1, CHCl3)Source of chirality: d-mannitol and asymmetric synthesisAbsolute configuration: (8S,9S,10R)

1,2:3,4-Di-O-isopropylidine-(2R,3R,4S)-5-chloropentane-1,2,3,4-tetraolC11H21ClO4[α]D25=+12.9 (c 1.1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2R,3R,4S)

(1S)-1-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]-2-propen-1-olC8H14O3[α]D25=+2.9 (c 1.1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1S,4R)

(4R)-4-[(1S)-1-(Benzyloxy)-2-propenyl]-2,2-dimethyl-1,3-dioxolaneC15H20O3[α]D25=+49.5 (c 1.1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1S,4R)

(2R,3S)-3-(Benzyloxy)-4-pentene-1,2-diolC12H16O3[α]D25=+54.5 (c 1.1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2R,3S)

(2R,3S)-3-(Benzyloxy)-1-[1-methyl-1-(1,1,1-trimethylsilyl)ethoxy]-4-penten-2-olC30H18O3[α]D25=+26.5 (c 1.1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2R,3S)

(2R,3S)-2,3-Di(benzyloxy)-4-penten-1-olC19H22O3[α]D25=+60.4 (c 1.1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2R,3S)