RESUMO
Stereochemical evidence is presented to demonstrate that (-)-inthomycin C has (3R)- and not (3S)-stereochemistry. Careful reappraisal of the previously published work2-5 now indicates that the Hatakeyama, Hale, Ryu, and Taylor teams all have synthesized (-)-(3R)-inthomycin C. The newly measured [α]D of pure (-)-(3R)-inthomycin C (98% ee) is -7.9 (c 0.33, CHCl3) and not -41.5 (c 0.1, CHCl3) as was previously reported in 2012.
Assuntos
Oxazóis/química , Estrutura Molecular , EstereoisomerismoRESUMO
Herein a new double O-directed free radical hydrostannation reaction is reported on the structurally complex dialkyldiyne 11. Through our use of a conformation-restraining acetal to help prevent stereocenter-compromising 1,5-H-atom abstraction reactions by vinyl radical intermediates, the two vinylstannanes of 10 were concurrently constructed with high stereocontrol using Ph3SnH/Et3B/O2. Distannane 10 was thereafter elaborated into the bis-vinyl iodide 9 via O-silylation and double I-Sn exchange; double Stille coupling of 9, O-desilylation, and oxidation thereafter furnished 8.
Assuntos
Alcinos/química , Compostos Heterocíclicos/síntese química , Macrolídeos/síntese química , Radicais Livres/química , Compostos Heterocíclicos/química , Macrolídeos/química , Conformação Molecular , Estrutura Molecular , Compostos Orgânicos de Estanho/química , Oxirredução , Compostos de VinilaRESUMO
A new pathway to (+)-inthomycin C is reported that exploits an O-directed free radical hydrostannation reaction on (-)-12 and a Stille cross-coupling as key steps. Significantly, the latter process was effected on 19 where a gauche-pentane repulsive interaction could interfere. Our stereochemical studies on the alkynol (-)-12 and the enyne (+)-7 confirm that Ryu and Hatakeyama's (3S)-stereochemical revision of (+)-inthomycin C is invalid and that Zeeck and Taylor's original (3R)-stereostructure for (+)-inthomycin C is correct.
Assuntos
Alcinos/química , Oxazóis/síntese química , Catálise , Radicais Livres , Estrutura Molecular , Oxazóis/química , EstereoisomerismoRESUMO
We present the synthesis and selected physicochemical properties of several novel symmetrical and unsymmetrical alpha,omega-nucleobase mono- and bis-amide conjugated systems containing aliphatic, aromatic or saccharidic linkages. The final stage of the synthesis involves condensation of a subunit bearing carboxylic group with an amine subunit. 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) was found to be a particularly effective condensing agent. The subunits containing carboxylic groups were obtained by acidic hydrolysis of N-1 Michael adducts of uracils or N-9 Michael adducts of 6-chloropurine with methyl acrylate. The amines used were aliphatic/aromatic diamines, adenine, 5-substituted 1-(ω-aminoalkyl)uracils and 5'-amino-2',5'-dideoxythymidine. The title compounds may find application as antiprotozoal agents. Moreover, preliminary microscopy TEM studies of supramolecular behaviour showed that target molecules with bolaamphiphilic structures were capable of forming highly ordered assemblies, mainly nanofibres.