Synthesis and oxidation of N-aminoglyconolactams:: A synthesis of mannostatin A

The N-amino-ribono-1,5-lactam 4 was prepared in two high-yielding steps from the known methanesul- V fonate 2. Oxidation of 4 with t-BuOCl in the presence of 2,6-lutidine afforded the tetrazene 6 (63%). Oxidation with MnO2 gave the deaminated lactam 7 (40%), which was also obtained, together with the lactone 8, upon oxidation of 4 with PhSeO2H. Oxidation with Mn(OAc)(3)/Cu(OAc)(2) provided the lactam 7 as the major and the dimer 9 as the minor product. Oxidation of 4 with 3 equiv. of Pb(OAc)(4) in toluene at room temperature gave two cyclopentanes, viz. the acetoxy epoxide 10 and the diazo ketone 11 in a combined yield of 78%. Oxidation with Pb(OBz)(4) provided 11 and the crystalline benzoyloxy epoxide 12. The crystal structure of 12 was established by X-ray analysis. The N-amino-glyconolactams 41, 46, and 51 were prepared similarly to 4. Their oxidation with Pb(OAc)(4) provided the diazo ketones 56, 57. and 58 as the only isolable products. Oxidation of the N-amino-mannono-1,5-lactam 55 with Pb(OAc)(4) in the presence of DMSO gave the sulfoximine 59. Mannostatin A, a strong alpha-mannosidase inhibitor, was synthesized from the acetoxy epoxide 10 (obtained in 48% from 4) in seven steps and in an overall yield of 45%.