In May 1991 I was an undergraduate student of prof. Nicotra at Milan University, Italy. I was working on my degree thesis in organic chemistry and I was stuck
in the synthesis of the molecule 9, when I get the molecule 10 thanks to serendipity.
For this research, Nicotra offered me a coffee at Wanda's bar in via Celoria/Golgi in Milan.
In 1993 the Nicotra research group published the article about azasugars (also known as iminosugars):
Lay L., Nicotra F., Paganini A., Pangrazio C., Panza L.
A new procedure for the synthesis of azasugars
(1993) Tetrahedron Letters, 34 (28), pp. 4555-4558.
These authors have shown, for the first time, that the addition of Grignard reagents to N-benzyl and N-alkyl glycosylamines derived from perbenzylated pentofuranoses or hexopyranoses followed by a simple cyclization procedure afforded a short and convenient approach to imino-C-glycosides in the pyrrolidine and piperidine series [43,44]. The procedure is illustrated in Scheme 2 (see compounds 1–6) from a d-arabinofuranosylamine, using octylmagnesium bromide, and from a d-glucopyranosylamine using allylmagnesium bromide, and cyclization promoted by reacting the intermediate amino alditol with triflic anhydride.
A first application of this reaction to the synthesis of azasugars was described in 1993 by the same authors, which opened the route to a new and efficient synthetic procedure towards this type of compounds.
This observation opened the way to an easy formation of azasugars following the sequence of a ) glycosylamine formation, b) Grignard reaction.
and c ) cyclization with Tf2O. This procedure is easily extended to include pyranose rings.
The synthesis of iminosugars via additions to glycosylamines was pioneered by the work of Nicotra and co-workers in the early 1990s. Several research groups have adopted Nicotra’s method for the synthesis of a wide variety of iminosugars with different configurations and substituents
It is amazing that such a small change – replacing an oxygen atom in a sugar molecule with a nitrogen atom – can have wide ranging therapeutic benefits.
