Total synthesis of patulolide C and 11-epipatulolide C

The total synthesis of 12-membered macrolides, patulolide C, 11-epipatulolide C and formal synthesis of patulolide A and epipatulolide A, starting from 1,8-octane diol is reported. A combination of Jacobsen’s hydrolytic kinetic resolution and Sharpless epoxidation is used for the creation of two stereogenic centres, while ring-closing metathesis strategy was used for the construction of the lactone ring.

Graphical abstractTotal synthesis of patulolide C and 11-epipatulolide C from 1,8-octane diol is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide

(8S)-8-(Methoxymethoxy)-9-decen-1-olC12H24O3[α]D = −148.2 (c 0.25, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (8S)

(2R,9S)-9-(Methoxymethoxy)-10-undecen-2-olC13H26O3[α]D = −177.6 (c 0.25, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,9S)

(2S,9S)-9-(Methoxymethoxy)-10-undecen-2-olC13H26O3[α]D = −2.6 (c 0.25, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,9S)

(1R,8S)-8-Hydroxy-1-methyl-9-decenyl acrylateC14H24O3[α]D = +11.5 (c 0.25, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,8S)

(1S,8S)-8-Hydroxy-1-methyl-9-decenyl acrylateC14H24O3[α]D = −12.7 (c 0.25, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,8S)

Patulolide CC12H20O3[α]D = +6.0 (c 0.25, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,11R)

11-Epipatulolide CC12H20O3[α]D = +3.6 (c 0.25, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,11S)