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Pseudosugars, 32. – Synthesis of 1,4‐Imino‐linked Carbadisaccharides Composed of a 2‐Amino‐5a‐carba‐2‐deoxyglucopyranosylamine Residue and Its Congeners
Author(s) -
Ogawa Seiichiro,
Tsunoda Hidetoshi
Publication year - 1993
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.1993199301121
Subject(s) - chemistry , aminocyclitol , residue (chemistry) , stereochemistry , amberlite , methylene , amino sugar , medicinal chemistry , organic chemistry , aminoglycoside , biochemistry , adsorption , antibiotics
Carbadisaccharide 5 , containing a 2‐acetamido‐5a‐carba‐2‐deoxyhexopyranosylamine residue, was synthesized by coupling of methyl 4‐amino‐4‐deoxy‐α‐ D ‐glucopyranoside ( 41 ) with the N ‐(2,4‐dinitrophenyl)epimino compound 16 followed by deprotection. The 6′‐acetamido‐6′‐deoxy analog 3 of a potent α‐glucosidase inhibitor methyl acarviosin ( 1 ) was synthesized from a condensate 50 obtained by coupling of 41 with the protected epimino compound 18 , possessing an exo ‐methylene function. This process involves a sequence of reactions: replacement by a benzoate ion and successive dehydrobromination of the dibromide 52 obtained from 50 . Hydroxymercuration of 50 followed by demetalation and deprotection gave two carbadisaccharide analogs 7 and 9 containing the valiolamine‐type branched aminocyclitol moieties. The free amines 4, 6, 8 , and 10 were prepared by treatment of the corresponding N ‐protected derivatives with Amberlite IRA 400 (OH − ) resin. Biological assays of all carbadisaccharides were carried out with three sugar hydrolases. Only compounds 6 and 8 were shown to be very weak α‐mannosidase inhibitors. The introduction of the acetamido or amino function instead of the hydroxyl group into the C‐6′ position of the methyl acarviosin analog 2 resulted in an appreciable decrease of the inhibitory activity.