Synthesis of glucuronic acid derivatives via the efficient and selective removal of a C6 methyl group

This investigation is related to the development of a general strategy for the synthesis of certain glucuronic acid derivatives. In particular, we report exceptionally selective conditions for removing the C6 methyl protecting group by potassium hydroxide without affecting the benzoyl protecting groups on the C2, C3 and C4 hydroxyl groups in high yields (95–99%). The present method proves to be efficient and environmentally friendly in terms of short reaction time, high yield and the single product.     

Synthesis of 2-iodoglycals, glycals, and 1,1'-disaccharides from 2-Deoxy-2-iodopyranoses under dehydrative glycosylation conditions

Treatment of 2-deoxy-2-iodopyranoses under dehydrative glycosylation conditions afforded pyranose glycals, 2-iodoglycals, and 1,1'-disaccharides instead of the expected glycoside products. While the product distribution revealed that this reaction is very sensitive to the configuration of the 2-deoxy-2-iodopyranose, 2-iodopyranoid glycals can be obtained almost exclusively in good yields by employing 3,4-O-isopropylidene as a cyclic bifunctional protecting group. The behavior of 2-deoxy-2-iodopyranoses during the dehydrative elimination reaction has been analyzed in detail.     

CO2-Enabled Cyanohydrin Synthesis and Facile Iterative Homologation Reactions**

Thermodynamic and kinetic control of a chemical process is the key to access desired products and states. Changes are made when a desired product is not accessible; one may manipulate the reaction with additional reagents, catalysts and/or protecting groups. Here we report the use of carbon dioxide to accelerate cyanohydrin synthesis under neutral conditions with an insoluble cyanide source (KCN) without generating toxic HCN. Under inert atmosphere, the reaction is essentially not operative due to the unfavored equilibrium. The utility of CO₂-mediated selective cyanohydrin synthesis was further showcased by broadening Kiliani–Fischer synthesis under neutral conditions. This protocol offers an easy access to a variety of polyols, cyanohydrins, linear alkylnitriles, by simply starting from alkyl- and arylaldehydes, KCN and an atmospheric pressure of CO₂.     

A general route toward the synthesis of the cladiellin skeleton utilizing a SmI2-mediated cyclization

An efficient synthesis of the cladiellin skeleton is reported utilizing methods that were previously developed in this laboratory. The approach is based on a SmI(2)-mediated cyclization reaction for the construction of the oxacyclononane unit. A [4 + 3] annulation strategy was used to create the octahydroisobenzofuran moiety. This route provides the cladiellin skeleton in only 14 steps without the use of protecting groups. The present approach also enabled the synthesis of the 3,7-diastereomer of the natural product polyanthellin A.     

A convenient oxazole C-2 protecting group: the synthesis of 4- and 5-substituted oxazoles via metalation of 2-triisopropylsilyloxazoles

[reaction: see text] Metalation of oxazoles at the 4 and 5 position was achieved after regioselective C-2 silyl protection. Removal of the protecting group was then accomplished under mild conditions allowing for a straightforward preparation of C-5 monosubstituted and C-4,5 disubstituted oxazoles. The first practical C-2 protecting group of oxazoles has been demonstrated.     

Visible‐Light‐Induced Direct Photocatalytic Carboxylation of Indoles with CBr4/MeOH

Photocatalysis enables the cascade reactions of indoles and CBr₄ in MeOH through a C(sp²)?H functionalization/methanolysis sequence. The title reaction provides an efficient access to indole 2‐ and 3‐carboxylates in a single operation (no preinstallation of protecting as well as directing groups was required) with good yields under mild reaction conditions.     

An unusual dehalogenation in the Suzuki coupling of 4-bromopyrrole-2-carboxylates

An unusual dehalogenation of 4-bromopyrrole-2-carboxylates under Suzuki coupling conditions has been observed. This dehalogenation can be suppressed by protection of the pyrrole nitrogen. Using a BOC protecting group, not only is dehalogenation suppressed, but the protecting group is also removed under the reaction conditions.     

4,6-O-[1-cyano-2-(2-iodophenyl)ethylidene] acetals. improved second-generation acetals for the stereoselective formation of beta-D-mannopyranosides and regioselective reductive radical fragmentation to beta-D-rhamnopyranosides. scope and limitations

The [1-cyano-2-(2-iodophenyl)]ethylidene group is introduced as an acetal-protecting group for carbohydrate thioglycoside donors. The group is easily introduced under mild conditions, over short reaction times, and in the presence of a wide variety of other protecting groups by the reaction of the 4,6-diol with triethyl (2-iodophenyl)orthoacetate and camphorsulfonic acid, followed by trimethylsilyl cyanide and boron trifluoride etherate. The new protecting group conveys strong beta-selectivity with thiomannoside donors and undergoes a tin-mediated radical fragmentation to provide high yields of the synthetically challenging beta-rhamnopyranosides. The method is also applicable to the glucopyranosides when high alpha-selectivity is observed in the coupling reaction and alpha-quinovosides are formed selectively in the radical fragmentation step. In the galactopyranoside series, beta-glycosides are formed selectively on coupling to donors protected by the new system, but the radical fragmentation is unselective and gives mixtures of the 4- and 6-deoxy products. Variable-temperature NMR studies for the glycosylation step, which helped define an optimal protocol, are described.     

Reactions of Sterically Protected 1-Halo- and 1-Pseudohalo-2-Phosphaethenyl-Lithiums

Abstract

Phosphorus analogs of alkylidenecarbenoid, Ar-P=C(X)Li, where X equals halogen or pseudohalogen atom, such as C1, Br, or SPh, have been generated by use of the 2,4,6-tri-t-butylphenyl group (abbreviated to Ar in the Scheme) as a protecting group for low coordinated organophosphorus compounds. The reaction with methyl iodide and with some aldehydes or ketones, at low temperature, gave the corresponding alkylation products^[l]. The reaction with copper salts gave 1,4-diphosphabutadiene (1) or 1,4-diphosphabutatriene (2), depending upon the substituent X^[2,3], as well as reaction conditions, such as reaction tenlperature and time, solvent, presence or absence of oxygen. Upon warming the phosphaethenyllithiun1s, thus generated, the chloro derivative of E-configuration gave a phosphaalkyne (3) via [1,2]-aromatic migration^[4], whereas the bromo derivative of Z-configuration gave a l-phospha-3,4-dihydronaphthalene derivative (4), that is a formal C-H insertion product of a phosphinidenecarbene intermediate^[5].     

2-(Prenyloxymethyl)benzoyl (POMB) as a new temporary protecting group for alcohols

The 2-(prenyloxymethyl)benzoyl (POMB) group was introduced in high yields to hydroxyl functions using the crystalline reagent, 2-(prenyloxymethyl)benzoic acid, in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). 2-(Prenyloxymethyl)benzoic acid is readily available, in two steps, from phthalide in 65% overall yield. The POMB group can be cleaved, in two steps, by treatment with 2,3-dichloro-5,6-dicyanoquinone (DDQ) followed by intramolecular lactonisation of the resulting hydroxy ester induced by a catalytic amount of Yb(OTf)₃·H₂O. The reaction conditions are compatible with the presence of a number of protecting groups such as isopropylidene, benzyl, acetyl, chloroacetyl, benzoyl, levulinoyl, Fmoc and Boc groups.     

New hydroxyl protecting groups of a safety-catch type removable by reductive acidolysis.

New hydroxyl protecting groups of a safety-catch type, i.e., 4-methylsulfinylbenzyl-oxycarbonyl (Msz) group for Tyr and 4-methylsulfinylbenzyl (Msob) ether for Thr, have been developed. O-Msz and O-Msob groups are stable under both acidic and basic conditions and can be removed by a one-pot reaction involving reductive acidolysis using tetrachlorosilane-trifluoroacetic acid (TFA)-scavengers. Using these new protecting groups, a 17 residue-peptide, gamma-endorphin, was successfully synthesized by the efficient solid phase method.     

Kinetics of the reaction between 2-phenylpropionitrile and 2-chloro-5-nitrotrifluoromethylbenzene under phase-transfer catalysis

Phase-transfer catalysis (PTC) is a widely accepted methodology in organic synthesis. Although a great number of organic syntheses were reported in PTC conditions, systematic kinetic studies are scarce. In the present report, a detailed study of the kinetics of the reaction between 2-chloro-5-nitrotrifluoromethylbenzene (CNTFB) and 2-phenylpropionitrile anion (HPP-), under PTC, was performed under several conditions. The reaction was carried out either in toluene or chlorobenzene as the organic phase, in the presence of a concentrated aqueous solution of NaOH using tetraalkylammonium (Q+X-) salts as phase-transfer catalysts. The major product was 2-(4-nitro-2-trifluoromethylphenyl)-2-phenylpropionitrile, and its yield depends on the experimental conditions. Different aspects of the mechanism are discussed and quantified. Kinetic data were explained by means of an interfacial mechanism that involves the deprotonation of the adsorbed nucleophile precursor followed by its catalyst-mediated extraction to the organic phase. A multicomponent Langmuir-type interface was assumed. Although the extraction of OH- by catalyst to the organic phase is usually disregarded, the formation of the substrate hydrolysis product that leads to catalyst poisoning was also investigated. The influence of this side reaction on the yield of the main product was established. A discussion about the influence of this side process on the main reaction and the operating mechanism is presented.     

Sulfur-based protecting groups for pyrroles and the facile deprotection of 2-(2,4-dinitrobenzene)sulfinyl and sulfonyl pyrroles

[reaction: see text] The effectiveness of simple sulfinyl and sulfonyl groups as electron-withdrawing protecting groups for pyrroles has been analyzed using (13)C NMR spectroscopy and confirmed by consideration of X-ray crystal structures. Additionally, the 2,4-dinitrobenzenesulfinyl and sulfonyl groups are shown to be effective electron-withdrawing protecting groups for pyrroles, and they can be removed by treatment with benzene thiol or thiolate under mild and specific conditions.     

Directing-protecting groups for carbohydrates. Design, conformational study, synthesis and application to regioselective functionalization

A novel concept of regioselective transformation of secondary hydroxyl groups in carbohydrates is presented. First, the relative reactivity of the free hydroxyl groups of onoprotected d-glucose derivatives was assessed using acetylation as a model reaction. As a result, acylation of these polyols gave a mixture of monosubstituted products in which the 3-O functionalized derivatives predominated. Novel hydrogen bond acceptor protecting groups were next designed to modulate the 4-OH and 3-OH reactivity in the hope to mediate higher regioselective transformations. A molecular modeling study later validated by spectroscopic analysis predicted additional intramolecular hydrogen bonds between the hydroxyl groups and pyridyl-containing protecting groups. Taking advantage of this induced hydrogen bond network, we achieved regioselective acetylation of the hydroxyl group at position 3 without protecting any secondary hydroxyl groups of the carbohydrate moiety. This designed protecting/directing group increased the nucleophilicity and the steric hindrance of position 3. As a result, optimization of the reaction conditions enabled the monoacetylation (not affected by steric hindrance) of 6-O-protected glucopyranosides at position 3 and selective silylation (affected by steric hindrance) of position 2 in high isolated yields and regioselectivities. This result certainly opens doors to the regioselective open glycosylation of carbohydrates.     

Synthesis of N-Substituted Benzimidazole-2-thiones

General methods were developed for N-substitution of benzimidazoline-2-thione with alkyl, alkenyl, alkynyl and acyl groups using S-tritylation as a protecting reaction.     

Thermolytic properties of 3-(2-pyridyl)-1-propyl and 2-[N-methyl-N-(2-pyridyl)]aminoethyl phosphate/thiophosphate protecting groups in solid-phase synthesis of oligodeoxyribonucleotides

Thermolytic groups may serve as alternatives to the conventional 2-cyanoethyl group for phosphate/thiophosphate protection in solid-phase oligonucleotide synthesis to prevent DNA alkylation by acrylonitrile generated under the basic conditions used for oligonucleotide deprotection. Additionally, thermolytic groups are attractive in the context of engineering a "heat-driven" process for the synthesis of oligonucleotides on diagnostic microarrays. In these regards, the potential application of pyridine derivatives as thermolytic phosphate/thiophosphate protecting groups has been investigated. Specifically, 2-pyridinepropanol and 2-[N-methyl-N-(2-pyridyl)]aminoethanol were incorporated into deoxyribonucleoside phosphoramidites 7a-d and 9, which were found as efficient as 2-cyanoethyl deoxyribonucleoside phosphoramidites in solid-phase oligonucleotide synthesis. Whereas the removal of 3-(2-pyridyl)-1-propyl phosphate/thiophosphate protecting groups from oligonucleotides is effected within 30 min upon heating at 55 degrees C in concentrated NH4OH or in an aqueous buffer at pH 7.0, cleavage of 2-[N-methyl-N-(2-pyridyl)]aminoethyl groups occurs spontaneously when their phosphate or phosphorothioate esters are formed during oligonucleotide synthesis. The deprotection of these groups follows a cyclodeesterification process generating the bicyclic salts 13 and 14 as side products. These salts do not alkylate or otherwise modify any DNA nucleobases and do not desulfurize a phosphorothioate diester model under conditions mimicking large-scale oligonucleotide deprotection.     

磺化笼型介孔碳催化的1,1-二乙酸酯的选择性合成

以磺化的笼型介孔碳为催化剂温和、高效、高选择性地合成了缩羰基二乙酸酯. 在室温和无溶剂条件下,用磺化的笼型介孔碳作催化剂使醛类化合物与乙酸酐之间在5~12 min内反应生成1,1-二乙酸酯,产率高达89%~98%. 在相同条件下酮类化合物不会发生此反应. 反应后催化剂经过简单的处理即可回收利用,回收利用7次活性无明显降低.     

PAP-H2O2-HRP酶促反应产物光谱及电化学研究

前文［１］首次提出了以对氨基酚（ＰＡＰ）为底物的ＰＡＰ－Ｈ２Ｏ２－辣根过氧化物酶（ＨＲＰ）伏安酶联免疫分析新体系,并成功地应用于烟草花叶等植物病毒的血清学检测．在此之前,我们也曾报道过一些伏安酶联免疫分析新体系［２,３］．迄今,还没有人对 ＨＲＰ催化 Ｈ２Ｏ２氧化 ＰＡＰ的酶促反应进行过探讨．Ｐｒａｔｉ等［４］报道了在铜催化作用下,Ｏ２氧化对氨基酚生成３－［（４－个羟苯基）氨基」－４－（２－氨基－５－羟苯基）－６－［（４－羟苯基）亚胺基］－２,４－环己二烯基－１－酮．本文的实验结果与此文献不符． 为…     

Anodic coupling reactions: exploring the generality of Curtin-Hammett controlled reactions

Intramolecular anodic olefin coupling reactions can be compatible with the presence of dithioketal protecting groups even though the dithioketal oxidizes at a lower potential than either of the groups participating in the cyclization. In such cases, product formation is controlled by the Curtin-Hammett Principle. In this study, the generality of such reactions is examined along with the use of alternative reaction conditions to suppress unwanted side reactions.     

Synthesis of RNA using 2'-O-DTM protection

tert-Butyldithiomethyl (DTM), a novel hydroxyl protecting group, cleavable under reductive conditions, was developed and applied for the protection of 2'-OH during solid-phase RNA synthesis. This function is compatible with all standard protecting groups used in oligonucleotide synthesis, and allows for fast and high-yield synthesis of RNA. Oligonucleotides containing the 2'-O-DTM groups can be easily deprotected under the mildest possible aqueous and homogeneous conditions. The preserved 5'-O-DMTr function can be used for high-throughput cartridge RNA purification.