A new synthesis of the phytotoxic 10-membered lactone herbarumin I

Herbarumin I a phytotoxic 10-membered lactone has been synthesized from d-(−)-isoascorbic acid in 12 steps with an overall yield of 16.8%. The methodology involved in generating the stereogenic center at C-8 is a Sharpless asymmetric epoxidation, as well 1,2-asymmetric induction followed by macrolactonization via RCM.

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(R)-Ethyl 2-(benzyloxy)-2-((R)-2,2-dimethyl-1,3-dioxalan-4-yl)acetateC16H22O5[α]D20=+26.5 (c 2.0, MeOH)Source of chirality: d-(−)-isoascorbic acidAbsolute configuration: (2R,3R)

(R)-2-(Benzyloxy)-2-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-N-methoxy-N-methylacetamideC16H23O5[α]D20=+14.7 (c 1.8, MeOH)Source of chirality: d-(−)-isoascorbic acidAbsolute configuration: (2R,3R)

(R)-1-(Benzyloxy)-1-((R)-2,2-dimethyl-1,3-dioxalan-4-yl)but-3-en-2-oneC16H20O4[α]D20=+22.1 (c 1.2, MeOH)Source of chirality: d-(−)-isoascorbic acidAbsolute configuration: (4R,5R)

(1S,2S)-1-(Benzyloxy)-1-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)but-3-en-2-olC16H22O4[α]D20=+6.9 (c 1.3, MeOH)Source of chirality: d-(−)-isoascorbic acidAbsolute configuration: (3S,4S,5R)

(R)-4-((1S,2S)-1,2-Bis(benzyloxy)but-3-enyl)-2,2-dimethyl-1,3-dioxolaneC23H28O4[α]D20=+31.8 (c 2.7, MeOH)Source of chirality: d-(−)-isoascorbic acidAbsolute configuration: (3S,4S,5R)

(2R,3S,4S)-3,4-Bis(benzyloxy)hex-5-ene-1,2-diolC20H24O4[α]D20=+47.8 (c 0.7, CHCl3)Source of chirality: d-(−)-isoascorbic acidAbsolute configuration: (2R,3R,4S)

(R)-2-((1S,2S)-1,2-Bis(benzyloxy)but-3-enyl)oxiraneC20H22O3[α]D20=+26.2 (c 2.6, MeOH)Source of chirality: d-(−)-isoascorbic acidAbsolute configuration: (2R,3R,4S)

(4R,5R,6S)-5,6-Bis(benzyloxy)oct-7-en-4-olC22H28O3[α]D20=+9.1 (c 3.0, MeOH)Source of chirality: d-(−)-isoascorbic acidAbsolute configuration: (4R,5R,6S)

(4R,5R,6S)-5,6-Bis(benzyloxy)oct-7-en-4-yl hex-5-enoateC28H36O4[α]D20=+6.4 (c 2.6, MeOH)Source of chirality: d-(−)-isoascorbic acidAbsolute configuration: (4R,5R,6S)

(8S,9R,10R,E)-8,9-Bis(benzyloxy)-10-propyl-3,4,5,8,9,10-hexahydro-2H-oxecin-2-oneC26H32O4[α]D20=+13.5 (c 1.1, MeOH)Source of chirality: d-(−)-isoascorbic acidAbsolute configuration: (8S,9R,10R,E)

Herbarumin IC12H20O4[α]D20=+11.5 (c 0.5, EtOH)Source of chirality: d-(−)-isoascorbic acidAbsolute configuration: (8S,9S,10R,E)

(R)-Ethyl 2-(tert-butyldimethylsilyloxy)-2-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)acetateC15H30O5Si[α]D20=+24 (c 1.5, CHCl3)Source of chirality: d-(−)-isoascorbic acidAbsolute configuration: (2R,3R)

(S,E)-4-(tert-Butyldimethylsilyloxy)-4-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)but-2-en-1-olC15H30O4Si[α]D20=+6.9 (c 4.0, MeOH)Source of chirality: d-(−)-isoascorbic acidAbsolute configuration: (4S,5R,E)

((2R,3S)-3-((R)-(tert-Butyldimethylsilyloxy)((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)oxiran-2-yl)methanolC15H30O5Si[α]D20=+15.5 (c 4.0, MeOH)Source of chirality: d-(−)-isoascorbic acidAbsolute configuration: (2R,3S,4S,5R)

(1S,2S)-1-(tert-Butyldimethylsilyloxy)-1-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)but-3-en-2-olC15H30O4Si[α]D20=+27.7 (c 1.5, MeOH)Source of chirality: d-(−)-isoascorbic acidAbsolute configuration: (2R,3S,4S)