Glycals in organic synthesis: a systematic strategy for preparation of uncommon piperidine 1,2-dideoxy-L-azasugars and 2-deoxy-1,5-anhydro-L-hexitols

A systematic synthetic strategy has been developed for producing uncommon piperidine 1,2-dideoxy-L-azasugars. This method involves the formation of open intermediates such as 2, 7, and 10 easily by ring-opening of D-glycals with aqueous mercury(II) acetate/sodium borohydride. A concise sequence of regioselective amination and cyclization reactions then allowed us to prepare the cyclic compounds 5a and 5b, L enantiomers of naturally occurring fagomine congeners such as 3-epi-fagomine (II) and 3,4-di-epi-fagomine (III), from Dglucal and D-galactal, respectively. The unnatural 3,4-di-epi-6-deoxyfagomine 9 was obtained from L-rhamnal by the same reaction sequence. This straightforward chemistry has been shown to be useful for preparing glycosyl derivativesof 1,2-dideoxy-L-azasugars starting from glycosyl glycals such as D-lactal, D-cellobial, D-maltal, and D-melibial, thus avoiding the usually lengthy glycosylation procedures. The flexibility of our protocol has been demonstrated by the easy conversion of the above-described open intermediates into uncommon 2-deoxy-1,5-anhydro-L-hexitols, never previously described.