Synthesis of N-aryl spiro-sulfamides as potential glycogen phosphorylase inhibitors

Cascade N-Alkylation/Hemiacetalization for Facile Construction of the Spiroketal Skeleton of Acortatarin Alkaloids with Therapeutic Potentiality in Diabetic Nephropathy

“…The three-step sequence [ 18 ] with assistance of microwave for the Vilsmeier–Haack formylation [ 19 ] proceeded well to afford 11 in 45 % yield (Scheme 4 ). To our delight, 12a (nearly 1/1 diastereoisomers) was generated directly in about 40 % yield using NaH [ 10 ] with unanticipated formation of semiacetal ring which was confirmed by 1D and 2D NMR. From the more bulky 10b , reaction did not afford 13 at room temperature.…”

“…Based upon the proposed biogenesis of acortatarins [ 2 ], we envisaged the chemoselective Amadori rearrangement to get the furanoid amino sugars, but our attempts did not give acceptable preparative yields (see supporting information). The work of Morin [ 9 ] and Wadouachi [ 10 ] made us recognize that the iodomethyl group acts as an interchanging hydroxymethyl or aminomethyl synthetic equivalent (Scheme 1 ). At the meanwhile, we noticed that the regioselective protection of fructofuranosyl acceptors directly from d -fructose needs time-consuming long process [ 11 ].…”

“…Enlightened by Araújo’s successful access to furanoside [ 12 ], an alternative retrospective route was outlined to obtain the key intermediates 3 a and 3 b from the readily available 2-deoxy- d -ribose ( 4a ) [ 13 ] and d -arabinose ( 4b ) [ 14 ], respectively. Similar to the protocol of Tan [ 7 ], the subsequently direct S N 2 coupling with pyrrole partner 5 [ 10 ] could bridge the two subunits (Scheme 2 ). We reasoned that this plan might offer additional strategic advantages in that all the requisite stereochemistry of the hydroxyl groups for 1 and 2 would be attained or kept along with the initial natural aldoses from the beginning to the end.…”

“…The combined organic phase was washed with brine, dried over Na 2 SO 4 , filtered and evaporated to dryness. After purification by flash chromatography on silica gel, the lactol 12a (nearly 1/1 diastereoisomers) was provided as pale yellow oil [ 10 ]. Yield: 22 mg (42 %).…”

Glycosidase inhibitors: versatile tools in glycobiology

“…101 The spiranic sulfamides were obtained starting either from exo-glucal 173, or from glucoronolactone 174, which were converted into b-aminoalcohols 175 (Scheme 23); treatment of 175 with a Burgess-type reagent furnished the spiro-sulfamides 176 (Scheme 23). 100 The p-anisyl derivative 177a showed good inhibition against muscle GPb, with a K i of 15 mM (Table 3).…”