Regioselective Monophosphorylation of Primary OH Groups in the Presence of Secondary OH Groups

With various model hydroxy compounds as examples, efficient procedures were developed for regioselective monophosphorylation of primary hydroxy groups in the presence of unprotected secondary hydroxy groups.     

Chiral Benzazaborole-Catalyzed Regioselective Sulfonylation of Unprotected Carbohydrate Derivatives

Chiral benzazaborole-catalyzed regioselective sulfonylations of unprotected carbohydrate derivatives have been developed. This methodology enables direct regioselective functionalization of the secondary OH group in carbohydrate in the presence of the primary OH group. By using the chiral organoboron catalysis, kinetic resolution of the carbohydrate derivatives was also achieved.     

Regioselective reduction of 2-perfluoroalkanoylcyclohexane-1,3-diones and their enamino derivatives

Ionic hydrogenation of 2-perfluoroalkanoylcyclohexane-1,3-diones and their endocyclic enamino derivatives containing a secondary amino group by the action of triethylsilane in trifluoroacetic acid in the presence of a catalytic amount of lithium perchlorate involved regioselective reduction of the side-chain carbonyl group to hydroxy with formation of the corresponding hydroxy diketones and hydroxy amino ketones, respectively. Under analogous conditions endocyclic enamino derivatives possessing a tertiary amino group underwent deacylation to give enamino ketones.     

Iterative, orthogonal strategy for oligosaccharide synthesis based on the regioselective glycosylation of polyol acceptors with partially unprotected n-pentenyl-orthoesters: further evidence for reciprocal donor acceptor selectivity (RDAS)

An efficient iterative, orthogonal protocol based on the regioselective glycosyl coupling of D-mannose polyols with, partially unprotected, n-pentenyl orthoester donors permits the synthesis of linear and branched oligosaccharides with minimal protecting group tampering.     

Highly chemo- and regioselective phosphitylation of unprotected 2′-deoxyribonucleosides

We have developed the chemo- and regioselective phosphitylation of unprotected 2′-deoxyribonucleosides by the use of di-tert-butyl N,N-diethylphosphoramidite, a sterically hindered phosphoramidite. Both N/O- and primary hydroxy group-selectivities were simultaneously achieved, and the selectivity for the 5′-hydroxy groups was up to 97% regardless of the base moiety of the 2′-deoxyribonucleosides. The 3′-O-isomers and the 5′-O-isomers were easily separated by silica gel column chromatography or crystallization to give the pure 2′-deoxyribonucleoside 5′-phosphites in moderate to good yields.     

Catalyst-controlled reversal of chemoselectivity in acylation of 2-aminopentane-1,5-diol derivatives

Highly chemo- and regioselective acylation of 2-aminopentane-1,5-diol derivatives has been achieved by organocatalysis. An acyl group can be chemoselectively introduced onto the sterically hindered secondary hydroxy group in the presence of the primary one by virtue of the molecular recognition event of the catalyst.     

用不保护或少保护的糖基受体合成寡糖*

用不保护或少保护的葡萄糖、甘露糖、鼠李糖作为糖基受体,经由糖原酸酯的中间体,能高区选和立体选地合成寡糖. α-(1→6)-连接的甘露寡糖、β-(1→6)-连接的葡萄寡糖、3,6-支化的甘露寡糖及葡萄寡糖用此方法能用很简单步骤合成,如具有重要生物活性的寡糖植保素激活剂葡萄六糖、具有抗肿瘤活性的香菇多糖的活性片段,以及一些具有重要生理功能的多糖的重复单元等.本文同时简述了用少保护的半乳糖和氨基葡萄糖为糖基受体合成寡糖的进展.     

Late-Stage Direct o-Alkenylation of Phenols by PdII-Catalyzed C−H Functionalization

o-Alkenylation of unprotected phenols has been developed by direct C−H functionalization catalyzed by Pd^II. This work features phenol group as a directing group and realizes highly site-selective C−H bond functionalization of phenols to achieve the corresponding products in moderate to excellent yields at 60 °C. The advantages of this reaction include unprecedented C−H functionalization using phenol as a directing group, high regioselectivity, good substrate scope, mild reaction conditions, and high efficiency. To the best of our knowledge, this is the first example of a regioselective C−H alkenylation of unprotected phenols utilizing phenolic hydroxyl group as a directing group. The alkenylation of unprotected tyrosine and intramolecular cyclization are also successfully carried out under this catalytic system in good yields. Furthermore, this novel method enables a late-stage modification of complex phenol-containing bioactive molecules toward a diversity-oriented drug discovery.     

A new strategy for the regio- and stereoselective hydroxylation of trans-2-aminocyclohexenecarboxylic acid

A simple and novel method for the introduction of an extra hydroxy group into an aminocyclohexanecarboxylic acid via stereoselective epoxidation and regioselective opening of the oxirane ring is presented. This method permits the preparation of the enantiomerically pure hydroxylated amino acid.     

Synthesis of Methylene Tetrahydrofurane-Fused Carbohydrates

A reliable method is disclosed to introduce a fused methylene tetrahydrofuran ring into carbohydrates. The resulting bicyclic saccharides can be used as scaffolds in medicinal chemistry and drug design. In addition, the enol ether functionality serves as a handle that enables modification in biological systems via photoclick chemistry. The approach is based on the regioselective oxidation of the C-3 hydroxy group in gluco-configured pyranosides, followed by stereoselective indium-mediated allylation. The ring formation is induced by an iodocyclization reaction with a neighboring hydroxy group. Subsequent dehydrohalogenation affords the desired methylene-tetrahydrofuran-containing carbohydrates.     

Perfectly regioselective acylation of a cardiac glycoside, digitoxin, via catalytic amplification of the intrinsic reactivity

Organocatalytic regioselective acylation of digitoxin has been developed. This method provides the 4′′′-O-manoacylate as the sole product without the concomitant formation of diacylates. The extremely high regioselectivity was assumed to be the result from the combined effects of the high intrinsic reactivity of C(4′′′)-OH and catalyst-promoted regioselective acylation of the same hydroxy group.     

Regioselective activation of glycosyl acceptors by a diarylborinic acid-derived catalyst

A derivative of diphenylborinic acid promotes catalytic, regioselective Koenigs-Knorr glycosylations of carbohydrate derivatives bearing multiple secondary hydroxyl groups. Robust levels of selectivity for the equatorial OH group of cis-1,2-diol motifs are demonstrated in reactions of seven acceptors derived from galactose, mannose, fucose, and arabinose using a variety of glycosyl halide donors. Catalyst control presents a new means of generating defined glycosidic linkages from unprotected or minimally protected carbohydrate feedstocks.     

Stereoselective hydrogenation of conjugate diene directed by hydroxy group and asymmetric synthesis of deoxypolypropionate units

Optically active cyclic compounds carrying a conjugate diene and two hydroxy groups were prepared through the intramolecular Büchner reaction with a chiral tether and succeeding stereoselective conversion. Hydrogenation of the diene in the first step was not regioselective but resulted in three regioisomeric monoenes. Nevertheless, the final saturated product carrying two stereogenic centers could be obtained in 98% stereochemical purity on further hydrogenation under optimized conditions. The high stereoselectivity throughout the multiple pathways is attributable to the effective direction by the hydroxy group. Ring cleavage of the produced stereochemically pure seven-membered ring compounds successfully resulted in synthetic intermediates for deoxypolypropionates.     

Approaches to intramolecular sialylation. 3. Synthesis of 2,4-dimethoxybenzyl ester of per-O-acetylated N-acetylneuraminic acid thioglycoside and its attempted oxidation with DDQ in the presence of nucleophiles

2,4-Dimethoxybenzyl ester of per-O-acetylated N-acetylneuraminic acid thioglycoside was synthesized and attempts at the oxidative (DDQ-induced) addition of O-nucleophiles (water and galactose derivatives with unprotected hydroxy group at C(6)) to the benzylic carbon atom of this ester were made.     

Synthesis of functionalized hydroxy-thiophene motifs as amido- and sulfonamido-phenol bioisosteres

Novel highly substituted hydroxy thiophene motifs were designed and synthesized as viable amido phenol and sulfonamido phenol bioisosteres. Hydroxy group-directed regioselective bromination and palladium-catalyzed amination of thienyl bromide via Buckwald protocol are the key elements of the synthetic approach. The hydroxy thiophene-containing compounds displayed good binding inhibitions.     

Application of DEPBT on the Synthesis of the Protected Dipeptides Containing Histidine with Unprotected Imidazole Group by Solution Method

3- (Diethoxyphosphoryloxy)- 1,2,3-benzotriazln-4 (3H)-one (DE-PBT) was an organophosphorus coupling reagent developed by our group. It was an effective coupling reagent for the synthesis of protected peptides containing Tyr, Ser and Thr with unprotected hydroxy group on their side chain. The further study of the synthesis of a series of protected dipeptides containing hisfidine with unprotected imidazole group using DEPBT is reported. During the synthetic procedure, the imidazole group of histidine did not need to be protected. When the carboxyl components were N-protected aromatic amino acids or basic amino acids, the yields were relatively high (63%--81%). However,when the carboxyl components were N-protected acidic amino acids, the yields were relatively low (47%--48%). The results expanded the application of DEPBT on the synthesis of bioactive peptides containing histidine.     

Enzymatic desymmetrization of a meso polyol corresponding to the C(19)-C(27) segment of rifamycin S

The stereoselective acylation of meso polyol 2 by vinyl acetate (solvent and acyl donor) in the presence of porcine pancreas lipase gave the corresponding monoester 5 in good yield (76%) and high enantiomeric purity (ee > 98%). The enzymatic reaction was also highly regioselective for a primary alcohol end group, and the two unprotected secondary alcohols were not involved. Compound 5 corresponds to the C(19)-C(27) fragment of rifamycin S.     

Aziridine-mediated ligation and site-specific modification of unprotected peptides

A synthesis of aziridine-containing peptides via the Cu(II)-promoted coupling of unprotected peptide thioacids and N-H aziridine-2-carbonyl peptides is reported. The unique reactivity of the resulting N-acylated aziridine-2-carbonyl peptides facilitates their subsequent regioselective and stereoselective nucleophilic ring-opening to give unprotected peptides that are specifically modified at the ligation site. The aziridine-mediated peptide ligation concept is exemplified using H(2)O as the nucleophile, producing a Xaa-Thr linkage (where Xaa can be an epimerizable and hindered amino acid). The overall process is compatible with a variety of unprotected amino acid functionality, most notably the N-terminal and Lys side chain amines.     

Direct azidation of unprotected carbohydrates under Mitsunobu conditions using hydrazoic acid

A single step procedure for the direct and regioselective synthesis of carbohydrate azides from unprotected sugars using hydrazoic acid under Mitsunobu conditions is reported. A series of mono-, di-, or triazido polyhydroxylated systems are described.     

Regioselective polymerization of divinyl sebacate and triols using lipase catalyst

The lipase‐catalyzed regioselective polymerization of divinyl sebacate and triols has been carried out. Immobilized lipase derived from Candida antarctica induces the polymerization of divinyl sebacate and glycerol, yielding a soluble polymer of relatively high molecular weight. NMR analysis showed that 1,3‐diglyceride is a main unit and the branching unit (triglyceride) is contained in the resulting polymer. These data indicate that the polymerization proceeds regioselectively to give the reactive polyester having a pendant hydroxy group.