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2′3′-cGAMP is an uncanonical cyclic dinucleotide where one A and one G base are connected via a 3′-5′ and a unique 2′-5′ linkage. The molecule is produced by the cyclase cGAS in response to cytosolic DNA binding. cGAMP activates STING and hence one of the most powerful pathways of innate immunity. cGAMP analogues with uncharged linkages that feature better cellular penetrability are currently highly desired. Here, the synthesis of a cGAMP analogue with one amide and one triazole linkage is reported. The molecule is best prepared via a first CuI-catalyzed click reaction, which establishes the triazole, while the cyclization is achieved by macrolactamization.

The C16′-C23′ fragments of enacyloxins, a series of antibiotics isolated from Frateuria sp. W-315, were synthesized from D-arabinose. Copyright by Walter de Gruyter Berlin Boston.

A method for preparing isofagomine, its derivatives, intermediates and salts thereof using novel processes to make isofagomine from D-(-)-arabinose and L-(-)-xylose.

A novel tartaric acid salt of Isafagomine (Isofagomine tartrate) that can be used for the treatment of Gaucher disease is provided. The invention also provides a crystalline form of isofagomine tartrate, method for preparing the salt, a pharmaceutical composition containing the salt, and a method of treating Gaucher disease.

Optically active 2-alkoxy-2H-pyran-3(6H)-ones (4a-d) were synthesized in one step by the tin(IV) chloride-promoted glycosylation and rearrangement of the 2-acetoxy-3,4-di-O-acetyl-D-xylal (3) prepared from D-xylose (1). The absolute configuration of the new stereocenter at C-2 was determined by chemical transformation of the dihydropyranones 4a and 4b into the known alkyl pentopyranosides (7a and 7b, respectively). Also, from 1H NMR experiments using a chiral ytterbium shift reagent, the enantiomeric excesses for 4a (> 86%) and 4b (>77%) were established. Enantiomerically pure 4c and 4d were obtained by reaction of 3 with chiral 2-octanol (R and S, respectively). Dihydropyranones 4a-d were employed as dienophiles in Diels-Alder cycloadditions with 2,3-dimethylbutadiene and butadiene. Under thermal conditions, only moderate yields (～50%) of cycloadducts 9a-c and 10a were respectively obtained with good diastereofacial selectivity (> 80%). Optimized Lewis acid promoted cycloadditions led to 9a-d and 10a,c in higher yields (～80%) and with higher diastereoselectivities (> 94%). The major products were formed by approach of the dienes from the less hindered face of the dihydropyranones, and the minor products (such as 11a) were formed by addition from the opposite side. Furthermore, cycloadduct 9a was stable in an alkaline solution, whereas 11a underwent epimerization under the same conditions.

A D-galactose analogue with a hydrazine in place of C-1 was synthesised.

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Full details of the total synthesis of pseudomonic acid C from L-lyxose are described.Key features of the approach involve feee-radical allylation for stereoselective C-C bond formation at C4 of lyxose, Frater alkylation to generate correct stereochemistry at C12 and C13, and stereoselective intramolecular Michael addition to establish the correct stereochemistry of the "anomeric" appendage.

A convergent total synthesis of pseudomonic acid C from L-lyxose is described in which a highly stereoselective free-radical C-C bond construction plays a key role.