ABSTRACT
The flavivirus methyltransferase (MTase) sequentially methylates the N-7 and 2'-O positions of the viral RNA cap (GpppA-RNAâm(7)GpppA-RNAâm(7)GpppAm-RNA), using S-adenosyl-l-methionine (SAM) as a methyl donor. We report here the synthesis and biological evaluation of a series of novel nucleoside analogs. Two of these compounds can effectively and competitively inhibit the WNV MTase with IC50 values in micromolar range and, more importantly, do not inhibit human MTase. The compounds can also suppress the WNV replication in cell culture.
Subject(s)
Methyltransferases/antagonists & inhibitors , Nucleosides/pharmacology , Viral Proteins/antagonists & inhibitors , West Nile Fever/virology , West Nile virus/enzymology , Down-Regulation , Humans , Methyltransferases/genetics , Methyltransferases/metabolism , Nucleosides/chemical synthesis , Viral Proteins/genetics , Viral Proteins/metabolism , Virus Replication/drug effects , West Nile virus/drug effects , West Nile virus/genetics , West Nile virus/physiologyABSTRACT
In situ-generated (bis-DPPMB)-Cu(OTf)(2) complex has been examined to catalyze a tandem olefin migration and Prins cyclization of an alkenol with various aldehydes. The reaction proceeded with electron-rich aromatic aldehydes at room temperature and provided functionalized tetrahydropyrans in good yields. An efficient synthesis of the bis-DPPMB ligand has also been described.
ABSTRACT
A stereoselective synthesis of (-)-viridiofungin A is described. The convergent synthesis utilized a unique highly diastereoselective multicomponent reaction between optically active phenyldihydrofuran and an α-ketoester to provide two chiral centers including a quarternary carbon center in a single step. Other key steps include an acyloxycarbonium ion-mediated tetrahydrofuran ring-opening reaction and a Julia-Kocienski olefination.
Subject(s)
Citrates/chemical synthesis , Titanium/chemistry , Tyrosine/analogs & derivatives , Molecular Structure , Stereoisomerism , Tyrosine/chemical synthesisABSTRACT
We developed a copper(II) triflate-bisphosphine complex catalyzed olefin migration and Prins cyclization which lead to the synthesis of substituted tetrahydropyran derivatives. The protocol is convenient and a variety of substituted tetrahydropyrans were obtained in good to excellent yields with excellent diastereoselectivities.
ABSTRACT
We have developed a practical synthesis of unique nucleoside derivatives via TiCl(4) promoted multicomponent reaction of optically active dihydrofuran, ethyl pyruvate/glyoxylate, and a TMS protected nucleobase in a single-pot operation.
Subject(s)
Nucleosides/chemical synthesis , Crystallography, X-Ray , Furans/chemical synthesis , Furans/chemistry , Glyoxylates/chemical synthesis , Glyoxylates/chemistry , Models, Molecular , Molecular Structure , Nucleosides/chemistry , Pyruvates/chemical synthesis , Pyruvates/chemistry , StereoisomerismABSTRACT
L-selectride reduction of a chiral or achiral enone followed by reaction of the resulting enolate with optically active alpha-alkoxy aldehydes proceeded with excellent diastereoselectivity. The resulting alpha,alpha-dimethyl-beta-hydroxy ketones are inherent to a variety of biologically active natural products.