Total synthesis of woodrosin I--part 1: preparation of the building blocks and evaluation of the glycosylation strategy.
The preparation of three building blocks required for the total synthesis of woodrosin I (1) is outlined, a complex resin glycoside bearing a macrolide ring which spans four of the five sugars of its oligosaccharide backbone. Key steps involve the enantioselective, titanium-catalyzed addition of dipentylzinc to 5-hexenal, the glycosylation of the resulting alcohol 18 with the glucose-derived trichloroacetimidate 7, and further elaboration of the resulting product 19 into disaccharide 22 on treatment with the orthogonally protected glycosyl donor 15. The trichloroacetimidate method is also used for the formation of the second synthon represented by disaccharide 38. A model study shows that the assembly of the pentasaccharidic perimeter of 1 depends critically on the phasing of the glycosylation events between fragments 22, 38 and the rhamnosyl donor 27 due to the severe steric hindrance in the product. A particularly noteworthy finding is the fact that diol 22 can be regioselectively glycosylated at the 3'-OH group in high yield without protection of the neighboring 2'-OH function.
Fürstner
Alois
A
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr, Germany. fuerstner@mpi-muelheim.mpg.de
Jeanjean
Fabien
F
Razon
Patrick
P
Wirtz
Conny
C
Mynott
Richard
R
D001671:Biochemistry / Q000379:methods*; D002240:Carbohydrate Sequence; D005227:Fatty Acids; D005960:Glucosides / Q000138:chemical synthesis* / Q000378:metabolism; D006031:Glycosylation; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000378:metabolism; D012210:Rhamnose / Q000737:chemistry
D005227:Fatty Acids; D005960:Glucosides; D009844:Oligosaccharides; C085563:woodrosin I; D012210:Rhamnose