We next aimed to develop a de novo synthesis of 1-thionoviose derivatives starting from commercially available a-D-methoxy mannose. In addition, orthogonal protection groups provide access to a modular route to synthesize 4-O-acyl derivatives of thionoviose. This is of particular interest as the 4-O-isobutyryl moiety of noviose contributes significantly to the biological activity. The key challenge starting from a-D-methoxy mannose is to introduce the gem-dimethyl group at C( ), which we envisioned to perform via a Grignard reaction of the lactone as reported by Hedberg et al. We decided to use an acetonide functionality for orthogonal protection of the 2,3-syn diol as this can be readily removed under the LA conditions of the substitution reaction at Fdx. We initiated our synthesis with the preparation of the literature known iodide 10 (Fig. ). tert-Butyldiphenylsilyl (TBDPS) protection of the C(4)-OH group proceeded smoothly with 76% yield. Elimination of the iodide afforded the exo-methylene 11 in a yield of 75%. Ozonolysis of the olefin 11 provided the lactone 12 in a yield of 70% which sets the starting point for the key Grignard reaction. The Grignard reaction with 2.7 equiv. of methylmagnesium chloride (MeMgCl) gave access to the C-skeleton of the targeted noviose derivative in 71% yield. Next, the anomeric OH-group of the hemiacetal was acetylated to afford compound 13 in a yield of 96% and a diastereoselectivity of ca. 8:2 (a:b).