Unsaturated analogs activity

The purpose of the present paper is to compare the toxicity and pharmacology of saturated compounds with their unsaturated analogs (wherever possible) and to list some important, physiologically active substances, bearing one or more double bonds. 

Anionic activation of Si—H bonds " by fluorides, such as KF or CsF, or by potassium phthalate, KHCO3, KSCN, etc., yields powerful hydridic reagents that reduce the carbonyl group of aldehydes, ketones and esters, " and 1,2-reductions of a,p-unsaturated aldehydes and ketones occur with high selectivity. " The analogous activation of hydridosllanes by fluoride ions is also achieved under acidic conditions with boron trifluoride etherate, in which the latter compound is consumed and fluorosilanes are formed. ... 

Cfxe.y prepared the 5,6-epithia-LTA4 60 by reaction of racemic LTA4 with sodium thiocyanate. Spur et al. prepared the same compound 60 as well as a number of olefin isomers, partially saturated and unsaturated analogs, from the corresponding epoxides via similar technology (Scheme 5.20). The compounds have shown we activity as inhibitors of SRS-A biosynthesis. 

The translational activity of various unsaturated analogs of L-isoleucine was evaluated using an Escherichia coli strain auxotrophic for isoleucine. It was observed that the alkene [2-amino-3-methyl-4-pentenoic acid (2)] and alkyne [2-amino-3-methyl-4-pentynoic acid (3)] derivatives of L-isoleucine can support protein synthesis at levels approximately 50% of that observed in cultures supplemented with isoleucine. However, no incorporation of the ocC or /JC methylated derivatives could be detected. In order to examine the stereoselectivity of incorporation, the (2S, 3S) and (2S, 3R) diastereomers of 2 and 3 were prepared. The extents of isoleucine substitution in vivo were 80% and 70% for (2S, 3S)-2 and (2S, 3S)-3, respectively, under the conditions examined in this study. 

Further, we cyclized the methyl group on the nitrogen with the CH2 of the ethoxy linker to form a hve- or six-membered ring (Scheme 19.4) to obtain compounds that showed activity superior to that of their parent molecules. The synthesis of these molecules is outlined in Scheme 19.5. The activity of these compounds to reduce blood glucose and triglyceride in db/db mice is shown in Table 19.2. It is observed that the cyclic linker moiety improved the antidiabetic activity of the compounds compared to the N— Me ethoxy linker. The unsaturated analogs showed better activity than that of their saturated counterparts. Benzyl-protected compounds have been found to be better than free OH compounds, despite losing antioxidant activity. Further, the benzopyran moiety in these molecules were shrunk to dihydrobenzofuran and benzofuran derivatives, which showed modest antidiabetic activities. 

The hydrogenations become analogous to those involving HMn(CO)5 (see Section II,D), and to some catalyzed by HCo(CN)53 (see below). Use of bis(dimethylglyoximato)cobalt(II)-base complexes or cobaloximes(II) as catalysts (7, p. 193) has been more thoroughly studied (189, 190). Alkyl intermediates have been isolated with some activated olefinic substrates using the pyridine system, and electronic and steric effects on the catalytic hydrogenation rates have been reported (189). Mechanistic studies have appeared on the use of (pyridine)cobaloxime(II) with H2, and of (pyridine)chlorocobaloxime(III) and vitamin B12 with borohydride, for reduction of a,/3-unsaturated esters (190). Protonation of a carbanion... 

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