Hydrazine derivatives condensation with sugars

In the synthesis of the glycolipid asialo GMI described by Ogawa and co-workers [107] the trisaccharide derivative (215) (used in the synthesis of asialo GM2) was converted into the 4,6-O-benzylidene derivative (233) and this was condensed with aceto-bromogalactose in the presence of mercury(II) cyanide and molecular sieves to give the P-linked acetylated galactose derivative in 97 % yield. The product was deprotected and acetylated to give the peracetyl derivative (234) of the tetrasaccharide which was converted into the free sugar (235) with hydrazine hydrate. Compound (235) was converted into asialo GMI via the imidate as described above for the synthesis of asialo GM2 from the imidate (219). 

A synthesis of MTX y-hydrazide (VIII.224) was described in 1981 by Rosowsky et al. [299], Condensation of MeAPA with y-methyl a-/-butyl L-glu-tamate with the aid of diethyl phosphorocyanidate afforded the diester (VIII.225) (76% yield), which was then converted sequentially to (VIII.226) (60% yield) on treatment with hydrazine in MeOH solution at 4 °C for 3 days and to (VIII.224) (45% yield) on hydrolysis with 1 M HCl at 50 °C for 1 h. Compound (VIII.224) has gained attention recently because of the opportunity it affords to couple MTX to monoclonal antitumour antibodies through the formation of semicarbazide bonds to periodate-oxidized sugars [331]. The y-hydrazide derivative (VIII.227) of AMT has also been cited briefly [332], although details of its synthesis have not yet been disclosed. 

Quinoxalines are an important class of nitrogen heterocyclic compounds, existing in pharmaceuticals and natural products. MW-assisted condensation of o-phenyl-enediamine with methylglyoxal or aldohexoses without addition of sodium bisulfite or hydrazine hydrate gave 689 in 95% yield within 120 s and sugar derivatives 690 and 691 in 60% yield within 270 s (Scheme 133) (02TL8371). 

A regioselective synthesis of 6-substituted pterins 729, 730, and 731 was achieved using an MW-assisted direct Isay-type condensation of triamine 728 with methyl-glyoxal or aldohexoses to give under MWI, without addition of sodium bisulfate or hydrazine hydrate, 729 in 70% yield within 62 s and the sugar derivatives 730 and 731 in 40% and 38% yields, respectively, within 270 s (Scheme 141) (02TL8371). 

The -(l-azido-napthalene-S-sulphonyl)-hydrazone derivative of lactose was Mcpared for photoaffinity labelling of a lectin from the conger eel. Aldose N-methyI-A -(4-phcnyI- and -p-substituted phenyl-thiazol-2-yl)hydrazones have been prepared and sqipear to have acyclic sugar residues. Tri- and penta-cyclic derivatives such as 92 and 93 were obtained by condensation of free sugars with A -(4-methylquinolin-2-yl)hydrazine or a tetracyclic heteroaromatic hydrazine, respectively, followed by cyclization (catalyzed by FeQa in EtOH). ... 

Pyrazole C-glycoside analogues, e.g. 75, were obtained by 1,3-dipolar cycloaddidon of alkenes u> nitrilimines, e.g. 74, formed from aldehydo-sugar hydrazones (Scheme 6). Mixtures of die 4-pyrazolol derivatives 76 and 77 (R = Me or Ph) woe synthesized by condensation of 3-ketoglucose with methyl- or phenyl-hydrazines with hydrazine itself, however, 4-pyrazolol 77 (R = H) was the sole product. ... 

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