Abstract: A process is disclosed for the production of cyclic di-guanosine monophosphate (c-di-GMP) without the use of protecting groups by means of an enzymatic synthesis. The process comprises the coupling of two guanosine triphosphate (GTP) molecules so as to form a c-di-GMP molecule. This is done under the influence of a mutant diguanylate cyclase (DGC) comprising the amino acid sequence V153M154G155G156. It has been found that the DGC is obtainable from inclusion bodies, and therewith can be made available in amounts sufficient to improve the c-di-GMP synthesis. Particularly, the latter synthesis can be conducted in a one-pot method starting from commercially available bulk chemicals and allows upscaling to a commercial production scale.

Abstract: This invention relates to a method for making macrolides, and, in particular, a method for making optionally substituted 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide and derivatives thereof, as well as uses of macrolides to make medicaments, methods of treatment using macrolides, and methods for making intermediates that, inter alia, may be used to make macrolides. This invention also relates to solvated and non-solvated crystalline forms of 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide, as well as methods for making such crystalline forms, medicaments comprising (or derived from) such crystalline forms, methods for making medicaments comprising (or derived from) such crystalline forms, methods of treatment using such crystalline forms, and kits comprising such crystalline forms.

Abstract: This invention relates to a method for making macrolides, and, in particular, a method for making optionally substituted 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide and derivatives thereof, as well as uses of macrolides to make medicaments, methods of treatment using macrolides, and methods for making intermediates that, inter alia, may be used to make macrolides. This invention also relates to solvated and non-solvated crystalline forms of 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide, as well as methods for making such crystalline forms, medicaments comprising (or derived from) such crystalline forms, methods for making medicaments comprising (or derived from) such crystalline forms, methods of treatment using such crystalline forms, and kits comprising such crystalline forms.