Conjugated products

In the presence of cationic initiators, the possibiUty for loss of pendant ether groups to form free alcohol is another side reaction that usually results in color formation because of the highly conjugated products formed. 

The metabolism of foreign compounds (xenobiotics) often takes place in two consecutive reactions, classically referred to as phases one and two. Phase I is a functionalization of the lipophilic compound that can be used to attach a conjugate in Phase II. The conjugated product is usually sufficiently water-soluble to be excretable into the urine. The most important biotransformations of Phase I are aromatic and aliphatic hydroxylations catalyzed by cytochromes P450. Other Phase I enzymes are for example epoxide hydrolases or carboxylesterases. Typical Phase II enzymes are UDP-glucuronosyltrans-ferases, sulfotransferases, N-acetyltransferases and methyltransferases e.g. thiopurin S-methyltransferase. 

No matter what the mechanism, if there is a double bond (C—C or C=0) or an aromatic ring already in the molecule that can be in conjugation with the new double bond, the conjugated product usually predominates, sometimes even when the stereochemistry is unfavorable (for an exception, see p. 1317). 

Haemophilus influenzae type b (Hib) vaccines currently in use are conjugate products, consisting of either a polysaccharide or oligosaccharide of polyribosylribitol phosphate (PRP) covalently linked to a protein carrier. 

Thus, the unsubstituted starting compound 69 was treated with resorcinol in the presence of trifluoroacetic acid (TFA) to yield 70. Then, reaction of 69 with the cyclic a,/3-unsaturated ketone in the presence of lithium hydride gave the 7-substituted heteroaromatic compound 71, and ethyl cyanoacetate afforded the cross-conjugated product 72, whereas reaction with pyrimidine-2,4,6-trione in the presence of triethylamine yielded the addition product 73. Indole also been reacted with 69, and heating of the dichloromethane solution for 90 min in the presence of TFA yielded the addition product 74 in excellent yield (95%) <1998ZOR450> (Scheme 12). 

It was recognized in early examples of nucleophilic addition to acceptor-substituted allenes that formation of the non-conjugated product 158 is a kinetically controlled reaction. On the other hand, the conjugated product 159 is the result of a thermodynamically controlled reaction [205, 215]. Apparently, after the attack of the nucleophile on the central carbon atom of the allene 155, the intermediate 156 is formed first. This has to execute a torsion of 90° to merge into the allylic carbanion 157. Whereas 156 can only yield the product 158 by proton transfer, the protonation of 157 leads to both 158 and 159. 

The attack of carbon nucleophiles such as Grignard reagents [116, 235, 236], cuprates [183, 237-242] and C-H acidic compounds [212] on allenes 155 leads generally to the non-conjugated products 158. However, it was observed early that 158 is the product of a kinetically controlled reaction also in these cases, whereas the thermodynamically more stable product 159 is formed at longer reaction times or subse-... 

An active glutathione S-transferase system was detected in the onion enzyme system when it was assayed with [ C]PCNB and GSH (9.). An initial rate of 14 nmol product/mg protein/hr was observed and a yield of 18 was obtained in 17 hr. HPLC indicated that S-(PCP)GSH was the only major conjugated product of this reaction. This was consistent with the Iji vivo studies with onion that showed that S-(PCP)GSH was the dominant GSH conjugate formed. In contrast, an enzyme from pea produced S-(PCP)GSH, S-(TCNP)GSH, and what appeared to be two isomeric S,S -(TCP)diGSH conjugates (6 ). 

In order to exploit the cycloaddition reactions of 2-vinylbenzofurans for natural product synthesis, the reactions of (E)-2-()S-methoxyvinyI)benzo-furans have been examined. The simplest compound (139, Scheme 36) on reaction with dimethyl acetylenedicarboxylate in boiling toluene gave a mixture of products. The major adduct was not the one expected but was its conjugation product 140. The diene system in 140 is able to react with... 

R = Me R = R = R = H, R = Me and R = R = H, R = R = Me) were reacted with the carbon electrophiles n-butyl, isopropyl and benzyl bromides, and isobutenyl chloride, in each case the alkylating agent attacked mainly at the carbon remote from the nitrogen, thus giving the conjugated product 82 (R = electrophile) with the double bond cis. Eth-oxide-catalyzed isomerization of 83 converted it to 84. °... 

Corticosteroid metabolites are excreted in the urine by the kidneys mainly as glucuronides and sulfates, but also as non-conjugated products. Small amounts of non-metabolized drugs are also excreted in the urine, while negligible amounts of most of the drugs are excreted in the bile. 

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