We postulate that the polymerization proceeds by electrophilic aromatic substitution; the dihydroxy(methy1)sulfonium cation (3) formed by protonation of the oxygen atom of the sulfinyl group serves as the active species (Scheme 2). 3 4 CH3 Scheme 2. Possible polymerization mechanisin for the formation of 1.The formation of 3 requires a strong protic acid such as trifluoromethanesulfonic acid (pK, = -14.5).[13] The sulfonium cation 3 reacts with a benzene unit to form a hydroxy(methy1)phenylsulfonium cation (4>, and successive electrophilic substitution results in the formation of poly(methylsu1fonio-1,4phenylene salt). It has not been clarified why electrophilic substitution of 4 occurs at the para position.r141 The electron-donating property of the lone pair of the sulfonium group through 3d-2p resonance might predominate over the electron-withdrawing effect in a strongly acidic media in analogy to electrophilic substitutions with aromatic sulfoxide.[' Experimentul Procedure 1 . (Typical polymerization procedure): To a solution of benzene (0 47 g, 6 mmol) in

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The synthesis of a series of analogues of the a-glucosidase inhibitor 1-deoxynojirimycin (dNM, 1) and of the a-mannosidase inhibitor 1-deoxymannojirimycin (dMM, 3) is described. The ability of dNM, dMM and a series of N-alkylated dNM and dMM derivatives to interfere with biosynthesis, transport and maturation of the glycoprotein a ,-antitrypsin in human hepatoma HepG2 cells and with the syncytium-inducing capacity of HIV-infected cells was investigated. A strong correlation was observed between a-glucosidase inhibition found in HepG2 cells and antiviral activity in HIV-I-infected cells. N-Butyl-(35), N-pentyl-(38), N-benzyl-(41) and N-decyl-dNM (47) showed high activity in both assays. N-Decyl-dNM was active at 0.01 mM but showed drug-related cell toxicity at concentrations exceeding 0.1 mM. Branching of the N-alkyl side chain reduced the activity of dNM derivatives considerably. N-Benzyl-6-0-butyryl-dNM (42) and N-decyl-6-0-benzoyl-dNM (48) showed activity comparable to that of N-benzyl-dNM (41) and N-decyl-dNM (47), respectively. None of the dMM analogues prevented HIV-induced syncytia formation. The 3-hydroxyl group in dNM and in dMM plays a crucial role in the interaction of these drugs with the corresponding processing glycosidases: 3-0-methyl-dNM (49) and 3-0-methyl-dMM (56) were inactive in both assays. The plasma membrane constitutes a permeability barrier for castanospermine (CAS, 2), but not for dNM, since the activity of CAS in streptolysin-0-permeabilized HepG2 cells was significantly higher than that in intact HepG2 cells. Finally, an overview is given of structures, other than the many N-substituted derivatives that were described, related to dNM and dMM that have appeared in the literature in recent years.i' Present address: h Nomenclature and abbreviations: AIDS = Acquired immune&ficiency syndrome, Bn = benzyl, CAS = castanospermine (2), CI,. T M B = chlorine-3,3',S,S'-tetramethylbenzidine, d N M = 1deoxynojirimycin = 1,s-dideoxy-1 ,S-imino-D-glucitol (I), dMM = 1deoxymannojirimycin = 1,5-dideoxy-l,S-imino-D-mannitol (3), HIV = human immunodeficiency virus, HM = high mannose, 2.6-lutidine = 2,6.dimethylpyridine, SDS-PAGE = Sodium-dodecyl-sulphate poly.acrylamide-gel-electro~horesis, sw = swainsonine (4, triflate = trifluoromethane sulphonate.

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