Synthesis of 13C enriched sialyllactones and their characterization using isotope edited inverse detected NMR spectroscopy

The first synthesis of N-acetylneuraminic acid 1,7-lactone

“…Our results are in line with the results obtained by others 8,11 for the formation of peracylated 1,7-lactones and appear to support the brilliant mechanism postulated by Ogura and coworkers to explain the formation of their mixture of acylated 1,7-lactones. [11][12][13] According to these authors, the formation in sequence of two mixed anhydrides, between Neu5Ac 1 and the acylating agent occurs during the reaction.…”

“…[3][4][5][6][7] Its synthesis and characterization are therefore of some importance taking into account that there is just indirect evidence of its involvement in several biological events. [4][5][6][7][8] Moreover, the availability of the lactone 4a is important also for the assessment of suitable analytical methods for its qualitative and quantitative evaluation in glycoconjugated compounds after acid hydrolysis. Thus, we programmed and satisfactorily accomplished its synthesis by a procedure herein reported.…”

“…In our work, we did not consider the direct lactonization of Neu5Ac 1 by means of N,N-dicyclohexylcarbodiimide (DCC) in pyridine since it was reported that, in these conditions, a partial 1,4-intramolecular lactonization of Neu5Ac 1 occurs to afford a mixture of the bicyclic 1,4lactone 9,10 5a and of the starting Neu5Ac 1. We excluded also the lactonization mediated by usual acylic chlorides or anhydrides on the basis of the extensive work of Ogura and coworkers [11][12][13] and of Gervay et al 8,14,15 who reported the formation of a variety of peracylated and partially acylated 1,7-lactones 4b and 4c, and of peracylated 1,4-lactones 5b. Also some preliminary attempts to perform a direct chemoselective 1,7-lactonization of Neu5Ac 1, under catalysis of protic and aprotic acids, performed in our laboratory, were unsuccessful.…”

Intramolecular Lactones of Sialic Acids

“…In the 1980s and 1990s, two independent research groups (Ogura's and Gervay's teams) attempted to synthesize both the intramolecular 1,4-and 1,7-bicyclic lactones, obtaining them only in their protected form [67][68][69][70][71]. In particular, Ogura's group reported seeding results in the synthesis, structure elucidation, as well as in the mechanism of formation of these protected bicyclic lactones [71].…”

“…Its structure was previously incorrectly attributed, by Khorlin et al [73], to the 5-acetamido-2,6,7,8,9-penta-O-acetyl-3,5-dideoxy-D-glycero-D-galacto-2noneno-1,4-lactone 9, a protected monocyclic Neu5Ac 1,4-lactone, known as γ-lactone (see Section 2.3). The correct structure of the peracetylated 1,7-lactone of Neu5Ac 8 was clarified by combining In the 1980s and 1990s, two independent research groups (Ogura's and Gervay's teams) attempted to synthesize both the intramolecular 1,4-and 1,7-bicyclic lactones, obtaining them only in their protected form [67][68][69][70][71]. In particular, Ogura's group reported seeding results in the synthesis, structure elucidation, as well as in the mechanism of formation of these protected bicyclic lactones [71].…”