Polyethylene glycol derivatives preparation

In a subsequent investigation by the author [2] bi-functional polyethylene glycol derivatives, (II), were prepared. 

Hydroxyl/carboxylic acid terminated polyethylene glycol derivatives, (V), were prepared by Varshney [5] and used as intermediates. 

Azide- and acetylene-terminated polyethylene glycol derivatives were prepared by Wilson [6] and used in biomedical applications. 

Antithrombonic esters, including co-poly-(A,A -sebacoyl-bis-(L-leucine)-l,6-hexylene diester), (III), and polyethylene glycol derivatives, (IV), were prepared by Pacetti [3] and Hossainy [4], respectively, and used as bio-absorbable stent coatings. 

In other investigations by the author [1], an additional polyethylene glycol derivative, (I), was prepared and used to modify lucifer-yellow modified lysozyme and bovine serum albumin. 

Isothiocyanate-terminated polyethylene glycol derivatives, (II) and (III), were prepared by Smith [2] and Acharya [3], respectively, and were effective in selectively reacting with biomolecules including antibodies, enzymes, and proteins. 

Zalipsky, S. and Barany, G., Preparation of polyethylene glycol derivatives with two different functional groups at the termini. Polymer Preprints (American Chemical Society, Division of Polymer Chemistry), 1986, 27(1), 1-2. 

The same approach was readily adaptable to solid-phase synthesis. A small library of unnatural derivatives of 140 was prepared with variation of the configuration and nature of R1 and R4 and with substitution on the benzene ring <2000JC0186>. Three natural alkaloids, Verrucine A, B, and Anacine, were synthesized by a similar pathway and the pyrazino[2,l- ]quinazoline as opposed to the benzodiazepine structure of Anacine was proved <2001JNP1497>. Fiscalin B and other derivatives were prepared by solid-phase synthesis using polyethylene glycol (PEG) resin <2002USP6376667>. 

Janda, Bolm and Zhang generated soluble polymer-bound catalysts for the asymmetric dihydroxylation by attaching cinchona alkaloid derivatives to polyethylene glycol monomethyl ether (MeO-PEG) [84—87]. Since these polymeric catalysts like (24) are soluble in many common solvents they are often as effective as their small homogenous counterparts. Janda et al. prepared catalyst (24) in which two dihydroquinidine (DHQD) units were linked together by phthalazine and finally were attached to MeO-PEG via one of the bicyclic ring system moieties (Scheme... 

A fullercnce derivative attached to polyethylene glycol having an Mn of 12,000 Da was also prepared. 

Nakajima et al. (1) prepared liquid crystalline polyrotaxane derivatives containing the mesogenic group 4-cyano-4 -hydroxybiphenyl attached to the a-cyclodextrin component of linear polyethylene glycol containing an a-cyclodextrin inclusion complex with an adamantane termini. 

Nitrates. Thallous nitrate, a convenient source of other thallium(I) derivatives, eg, halides, is prepared from the reaction of the pure metal with dilute nitric acid (9). The solid is stable to 300°C and decomposes at 800°C to Tl O, NO, and N02. Thallic nitrate is obtained as a trihydrate upon dissolving T Oj in cold nitric acid. It decomposes to T C on heating to 100°C or upon hydrolysis. Thallic nitrate, soluble in alcohols and ethers of polyethylene glycols, is often used as an oxidizing agent in oiganic syntheses. 

H. Suppositories Solid preparations which melt at body temperature delivering medication for at-site treatment or for absorption at that point (usually rectal, vaginal, or urethral). Excipients include cocoa butter, waxy fatty acids, and derivatives, polyethylene glycol, theobroma oil, as well as many ingredients found in G. 

However, Yokoyama et al. (1994) reported that a ratio between the chemically conjugated and physically entrapped ADR (i.e., DOX) was not determined, and considerable amounts of adriamycin derivatives formed and were incorporated in the micelles. Yokoyama et al. (1998) quantitatively measured the ADR incorporated in the inner core using the improved synthetic method, and analyzed the effects of the ADR contents (both by chemical conjugation and physical entrapment) on micelle stability andn vivo antitumor activity. The copolymer used by Yokoyama et al. (1998) was polyethylene glycol)-fepoly(aspartic acid) block copolymer (PB P(Asp)). The chemical conjugation and physical entrapment methods can be referred to in the earlier section of preparation of polymeric micelles. 

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. 

Careful design was used by Seeman to prepare complementary DNA strands that self assemble into a cube with 20 nucleotide pairs along each edge. Other derivatives include nylon DNA , through the synthesis of peptide nucleic acids (PNA), and polyethylene glycol derivatized DNA. Figure 8.1 illustrates the DNA knots that can be prepared using these techniques. 

Roberts [8] prepared polyethylene glycol 2-pyridylthioester derivatives, (IV) for conjugating with a-amine polypeptides. 

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