Synthesis of chiral archaebacterial membrane lipid synthons.
Item
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Title
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Synthesis of chiral archaebacterial membrane lipid synthons.
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Identifier
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AAI9808023
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identifier
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9808023
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Creator
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Wu, Yanzhong.
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Contributor
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Adviser: W. F. Berkowitz
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Date
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1997
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Language
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English
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Publisher
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City University of New York.
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Subject
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Chemistry, Organic
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Abstract
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2,6-dimethyl 1,6-heptadiene has been synthesized with improved yield (65%) by cross coupling between 4-bromo-2-methyl-1-butene or the tosylate of 3-methyl-3-butene-1-ol with the Grignard reagent of 3-chloro-2-methylpropene in the presence of Li{dollar}\sb2{dollar}CuCl{dollar}\sb4.{dollar} Stereospecific cyclic hydroboration of the resulting diene with thexylborane, followed by carbonylation/oxidation gave mseo-3,7-dimethylcyclooctanone as a pure diastereoisomer in a one-pot synthetic procedure in 51% yield. The key step in the synthesis of the desired C{dollar}\sb{10}{dollar} chiron was the asymmetric deprotonation of mseo-3,7-dimethylcyclooctanone with the lithium salt of (+)-bis- ((R)-1-phenylethyl) amine and "internal quench" with excess trimethylsilylchloride to give (((3S,7R)-3,7-dimethyl-1-cyclo-octen-1-yl)oxy) trimethyl-silane in good yield (85%) and in high optical purity (98% ee). Ozonolysis reaction of the resulting enol silyl ether gave C{dollar}\sb{10}{dollar} chiron (3R,7S)-3,7-dimethyl-8-hydroxyoctanoic acid in 27% overall yield in 5 steps. We believe this chiron will be applicable to the synthesis of archaebacterial lipids.;Copper-catalyzed cross-coupling of alkylsamarium reagents with alkyl halides was investigated. SmI{dollar}\sb2{dollar}/HMPA converts alkyl iodides and bromides to alkylsamarium reagents which can be cross-coupled with primary iodides, bromides, and secondary iodides in the presence of Cu(I) halides or Li{dollar}\sb2{dollar}CuCl{dollar}\sb4{dollar} at room temperature. The alkylation of primary iodides gives high yields of cross-coupling products with negligible homo-coupling products. The method is especially useful for small scale cross-coupling reactions.;Archaebacterial lipid C{dollar}\sb{lcub}20{rcub}{dollar} chiron, methyl 16-((t-butyldiphenyl-silyl)oxy) -(3R,7R,11S,15S)-3,7,11,15-tetramethylhexadecanoate was synthesized by using both copper-catalyzed coupling of the Grignard reagent of 1-bromo-8-(t-butyldiphenylsilyloxy)-(2R,7S)-3,7-dimethyloctane with methyl (3R,7S)-3,7-dimethyl-8-iodooctanoate, and copper-catalyzed cross-coupling of the samarium reagent of 8-(t-butyldiphenylsilyloxy)-1-iodo-(2R,7S)-3,7-dimethyloctane with methyl (3R,7S)-3,7-dimethyl-8-iodooctanoate, in 71% and 81% yields, respectively. A C{dollar}\sb{lcub}20{rcub}{dollar} dibromide, 1,16-dibromo-(3R,7S, 10S, 14R)-3,7,10,14-tetramethylhexadecane was synthesized by copper-catalyzed Grignard homo-coupling of 1-bromo-8-(t-butyldiphenylsilyoxy)-(2S,6R)-2,6-dimethyloctane, followed by desilylation and bromination. A vitamin E side chain synthon, (3R,7R)-(+)-3,7,11-trimethyldodecan-1-ol (98% ee), was synthesized in 19% overall yield in 9 steps.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
