Nickel-catalyzed coupling producing (2Z)-2,4-alkadien-1-ols, conversion to (E)-3-alkene-1,2,5-triol derivatives, and synthesis of decarestrictine D.
The 3-alkene-1,2,5-triol structure is not only a major framework of biologically important molecules but also a new functional-group-rich unit for synthesis of polyols and sugars. A method furnishing such triol derivatives 8 was developed and successfully applied to synthesis of decarestrictine D (18). First, coupling reaction of the unprotected alcohols 2 with borates 4 was investigated to produce the dienyl alcohols 6 with NiCl2(dppf) in Et2O/THF (5:1) at room temperature. The hydroxyl-group-directed epoxidation of 6 followed by palladium-catalyzed reaction with AcOH (Scheme 1) furnished 3-alkene-1,2,5-triol derivatives 8. Since each step proceeded with high stereo- and regioselectivities, the stereochemistry of 8 has been correlated with the olefin geometry of 6. With the above transformation in mind, synthesis of the full carbon skeleton of decarestrictine D (18) could be designed easily and was completed successfully. Furthermore, a new seco acid 19b with the MOM protective group for the three hydroxyl groups was found to afford macrolide 48 in a yield higher than those reported previously.
Kobayashi
Yuichi
Y
Department of Biomolecular Engineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan. ykobayas@bio.titech.ac.jp
Yoshida
Shinya
S
Asano
Moriteru
M
Takeuchi
Akira
A
Acharya
Hukum P
HP
D000438:Alcohols; D000475:Alkenes / Q000138:chemical synthesis*; D001881:Borates / Q000737:chemistry; D002384:Catalysis; D004852:Epoxy Compounds / Q000138:chemical synthesis; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D007783:Lactones / Q000138:chemical synthesis*; D008094:Lithium / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009532:Nickel / Q000737:chemistry*; D010126:Ozone / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D000439:Pentanols / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000438:Alcohols; D000475:Alkenes; D001881:Borates; D004852:Epoxy Compounds; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007202:Indicators and Reagents; D007783:Lactones; D000439:Pentanols; C073577:decarestrictine D; D010165:Palladium; D010126:Ozone; D009532:Nickel; D008094:Lithium