Formal synthesis of kibdelomycin and derivatisation of amycolose glycosides

A convergent total synthesis of bacterial gyrase B/topoisomerase IV inhibitor kibdelomycin (a.k.a. amycolamicin) (1) was devised starting from inexpensive d-mannose and l-rhamnose, which were converted in new efficient ways to an N-acylated amycolose and an amykitanose derivative as late building blocks. For the former, we developed an expeditious, general method for the introduction of an α-aminoalkyl linkage into sugars via 3-Grignardation. The decalin core was built up in seven steps via an intramolecular Diels–Alder reaction. These building blocks could be assembled as published previously, making for a formal total synthesis of 1 in 2.8% overall yield. An alternative order of connecting the essential fragments was also made possible by the first protocol for the direct N-glycosylation of a 3-acyltetramic acid.