Glucuronidation of Two Novel Metabolites of Benproperine with Trichloroacetimidate Donor

The glucuronide metabolites of benproperine were synthesized from mono-hydroxylate metabolites of benproperine that were treated with methyl （2,3,4-tri-O-acetyl-1-O-tfichloroacetimidoyl ） -α-D-glucopyranuronate with BF3 · Eh O as the promoter followed by basic hydrolyzation with Na2 CO3. The form of basic acceptors, the order of addition, and the promoter are all important variables in this glucuronidation. The salt form of the basic acceptor was found to be better than its free form for glucuronidation with a Lewis acid as the promoter. Two mono-hydroxylated benproperines were synthesized from 2-benzylphenol in three steps.

Rhodium-Catalyzed Asymmetric Trifluoromethoxylation of Racemic Allylic Trichloroacetimidates

A rhodium/diene catalyzed asymmetric allylic trifluoromethoxylation reaction is reported,which afforded chiral trifluoromethoxylated allylic compounds in 52%–97%yields with up to 97%enantiomeric excess.These are the first examples of asymmetric allylic trifluoromethoxylation.The reactions proceed via a dynamic kinetic process that allowed for the use of racemic allylic trichloroacetimidates as substrates.Density functional theory calculations showed that the formation of the C–OCF_(3)bond occurs via outer-sphere nucleophilic attack.Importantly,the presence of the allylic group in the products enabled them to be converted into a diverse array of optically active trifluoromethylated molecules that are otherwise difficult to access.

Concise Synthesis of Lactococcus garvieae Lipoteichoic Acids Through an Additive-Modulated Preactivation Protocol and the Immunological Studies

Lipoteichoic acids(LTAs)are macroamphiphiles composed of alditol,lipid,phosphate,and carbohydrate units.Due to their inherent complexity,it is a severe challenge to access LTAs with structural integrity from natural sources for biological or immunological evaluation.Here,we describe the first total synthesis of Lactococcus garvieae LTA(type II LTA),containing five distinct 1,2-cis gluco/galactopyranosidic linkages,via a novel additive-modulated O-glycosyl trichloroacetimidate preactivation glycosidation strategy.This strategy features(1)high glycosidation yields and excellent 1,2-cis stereoselectivities independent of the donor anomeric configuration,(2)common and inexpensive reagents as promoters and additives,(3)application to standard glycosyl imidate donors without resorting to participating protection,and(4)general application to reactive and less reactive glycosyl acceptors.Thus,via the precise stereocontrolled construction of three galactopyranosidic and two glucopyranosidic bonds on a multigram scale,a series of structurally well-defined LTA molecules were successfully assembled.Immunological evaluation of these type II synthetic LTAs showed a structure–activity relationship in the stimulation of a proinflammatory response.

Synthesis of Analogues of the Antitumor (1→6)-Branched (1→3)-Glucohexaose

b-D-Glcp-(13)-[b-D-Glcp-(16)-]a-D-Manp-(13)-b-D-Glcp-(13)-[b-D-Glcp-(16)-]D-Glcp (18) and b-D-Glcp-(13)-[b-D-Glcp-(16)-]a-D-Manp-(13)-b-D-Glcp-(13)-[b-D-Glcp-(16)-]b-D-Glcp-D-(13)-Glcp-1OMe (29) were synthesized as the analogues of the immunomodulator b-D-Glcp-(13)-[b-D-Glcp- (16)-]a-D-Glcp-(13)-b-D-Glcp-(13)-[b-D-Glcp-(16)-]D-Glcp through coupling of trisaccharide donors 9 with trisaccharide acceptor 16 and tetrasaccharide acceptor 27 followed by deprotection, respectively.