Neomycin mimetics

Scheme 3.52), whereas the corresponding acetyl-protected donor gave little product under the same reaction conditions [512], Additionally, the trichloroacetimidate method has also been applied to synthesize other natural products, such as bupres-tin A and B [517], macrophylloside D [518] and neomycin mimetics [519]. 

Wong and co-workers [22] also applied the methodology in the preparation of a library of neomycin B mimetics (Fig. 6). Two libraries were prepared by a multiple-component condensation of neamine derived aldehyde, f-butyl isocyanide or isocyanoacetic acid methyl ester, CBZ-N amino acids (xl3) and a glycine conjugated polyethylene glycol methyl ether. The products of the reaction were isolated by precipitation. 

The neamine-derived aldehyde 81 has been prepared and used in combinatorial synthesis of a library of neomycin B mimetic aminoglycoside antibiotics, a strategy for the discovery of new inhibitors for binding to the Rev-responsive element of HIV mRNA [55], The synthesis involves allylation of the selectively protected neamine derivative 80, followed by ozonolysis of the allylic double bond to generate the aldehyde functional group (compounds 80, 81). 

The aldehyde 4 can be prepared from neomycin B, and this has been used in a combinatorial synthesis of neomycin B mimetics 5 (R = Bu or CH2C02Me, R = side-chains of 12 different aminoacids), using Ugi-type four-component conden-... 

LIGURE 11.8 Synthesis of neomycin B mimetics using four-component condensation. (From Park, W.K.C. et al., Rapid combinatorial synthesis of aminoglycoside antibiotic mimetics use of a polyethylene glycol-linked amine and a neamine-derived aldehyde in multiple component condensation as a strategy for the discovery of new inhibitors of the HIV RNA Rev responsive element, /. Am. Chem. Soc., 118, 10150, 1996.)... 

Library 4.10 Neomycin B mimetics Size 52 members Affiliation Wong, C.-H. et al. [78] Year 1996... 

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