TCP- and Phthalimide-Protected n-Pentenyl Glucosaminide Precursors for the Synthesis of Nodulation Factors As Illustrated by the Total Synthesis of NodRf-III (C18:1, MeFuc)

TCP- and phthalimide-protected n-pentenyl glucosaminide (NPG) precursors have been utilized in a convergent stereocontrolled synthesis of the nodulation factor NodRf-III (C18:1, MeFuc) produced by Rhizobium fredii USDA257, 2. Nodulation factors are lipooligosaccharides that are secreted by bacteria which trigger the early steps in the formation of root nodules in leguminous plants. This symbiotic relationship between plant and bacteria plays a major role in the global nitrogen cycle. Key to our synthetic approach was the use of the TCP (tetrachlorophthaloyl) group to provide for N-differentiation of the linear glucosamine backbone and the use of FeCl3 for the removal of benzyl protecting groups from the tetrasaccharide. The saccharide skeleton was assembled via the NPG-based coupling of a linear β(1→4) glucosamine disaccharide to a 6-O-fucosylated glucosamine acceptor. Significant yield enhancements for NPG couplings were observed at lower temperatures. Subsequent exchange of benzyl to tert-butyldimethyls...