Photolabile 2-(2-Nitrophenyl)-propyloxycarbonyl (NPPOC) for Stereoselective Glycosylation and Its Application in Consecutive Assembly of Oligosaccharides.

A photolabile protecting group (PPG) 2-(2-nitrophenyl)-propyloxycarbonyl (NPPOC) was explored in glycosylation and applied in the consecutive synthesis of oligosaccharides. NPPOC displays a strong neighboring group participation (NGP) effect to facilitate the construction of 1,2-trans glycosides in excellent yield. Notably, NPPOC could be efficiently removed by photolysis, and the deprotection conditions are friendly to typical protecting groups. A branched and asymmetric oligomannose Man6 was rapidly prepared, and the consecutive assembly of oligosaccharides without intermediate purification was further investigated owing to the compatibility conditions between NPPPOC's photolysis and glycosylation.

Organo-Catalyzed Regio- and Geometry-Specific Construction of ß-Hydroxyl-α-vinyl Carboxylic Esters: Substrate Scope, Mechanistic Insights, and Applications.

A green protocol has been developed for the synthesis of ß-hydroxyl-α-vinyl carboxylic esters using aldehydes and α,ß-unsaturated esters bearing an activated γ proton as starting materials under Morita-Baylis-Hillman (MBH) reaction conditions. Diverse ß-hydroxyl-α-vinyl carboxylic esters have been synthesized regiospecifically in moderate to good yields with only E geometric selectivity. Other remarkable features include atom efficiency, environmental benignancy, and mild reaction conditions. Furthermore, the reaction products could be readily converted into tetrahydrofuran, dihydrofuran, and furan derivatives.

Transition-Metal-Free Synthesis of 1,3-Butadiene-Containing π-Conjugated Polymers.

This work describes the synthesis of π-conjugated polymers possessing arylene and 1,3-butadiene alternating units in the main chain by the reaction of α,ß-unsaturated ester/nitrile containing γ-H with aromatic/heteroaromatic aldehyde compound. By using 4-(4-formylphenyl)-2-butylene acid ethyl ester as a model monomer, the different polymerization conditions, including catalyst, catalyst amount, and solvent, are optimized. The polymerization of 4-(4-formylphenyl)-2-butylene acid ethyl ester is carried out by refluxing in ethanol for 72 h with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a catalyst to give a 1,3-butadiene-containing π-conjugated polymer, poly(phenylene-1,3-butadiene), in 84.3% yield with M¯n and M¯w/M¯n (PDI) estimated as 6172 and 1.65, respectively. Based on this new methodology, a series of π-conjugated polymers containing 1,3-butadiene units with different substituents are obtained in high yields. A possible mechanism is proposed for the polymerization through a six-membered ring transition state and then a 1,5-H shift intermediate.

Novel ferrocene-based bifunctional amine-thioureas for asymmetric Michael addition of acetylacetone to nitroolefins.

An efficient method was developed to synthesize ferrocene-based bifunctional amine-thioureas bearing multiple hydrogen-bonding donors. Asymmetric Michael addition of acetylacetone to nitroolefins catalyzed by these novel bifunctional catalysts affords the Michael adducts in high yield and moderate to excellent enantioselectivities. Multiple hydrogen-bonds play an important role in accelerating the reaction.

Orthogonal Deprotection of Photolabile Protecting Groups and Its Application in Oligosaccharide Synthesis.

We herein report for the first time the inter- and intramolecular orthogonal cleavage of two ortho-nitrobenzyl (NB) analogues. It is shown that the nitroveratryl (NV) group can be photolyzed with high priority when NV and ortho-nitrobenzyl carbonate (oNBC) are used together as the protecting groups of glycans. Notably, the photolytic products could be used directly in the subsequent glycosylation without further purification. With the above-mentioned orthogonal photolabile protecting group strategy in hand, a Mycobacterium tuberculosis tetrasaccharide and a derivative of glucosyl glycerol were rapidly prepared.

Photosensitive Fluorous Tag-Assisted Convergent Synthesis of ß-1,4-Mannuronates.

Rapid synthesis of saccharides by a chemical method is an efficient way to meet the demand for well-defined glycans to probe their biological functions. Herein, a feasible and convenient strategy for saccharide synthesis was established by introducing a photosensitive fluorous tag at the anomeric position of glycosides. The tag was used not only in polytetrafluoroethylene-assisted rapid purification but also as a temporary protecting group at the reducing end of carbohydrates. The tag-protected glycosides could be transformed into new glycosyl donors for convergent synthesis after orthogonal deprotection of the tag by photolysis. Via combination of the ß-directing C-5 carboxylate glycosylation strategy, ß-1,4-mannuronates were efficiently prepared.

S-o-(p-Methoxyphenylethynyl)benzyl (SMPEB) Glycosides for Catalytic Glycosylation and Their Application in the Synthesis of Polyporus Umbellatus Polysaccharides.

We herein reported a new type of S-o-(p-methoxyphenylethynyl)benzyl donor for a highly efficient glycosylation method. The donor was activated by 10% Tf2O and underwent glycosylation with various acceptors to provide the corresponding glycosides in excellent yield. Furthermore, two repetitive fragments of Polyporus umbellatus polysaccharides (PUPs), isolated from traditional Chinese medicine "Polyporus umbellatus", were prepared by combining the "single-catalyst one-pot" and "latent-active" strategies for the first time for future clear studies on the structure-activity relationship of PUPs.

Synthesis of a 3-deoxy-D-manno-octulosonic acid (KDO) building block from D-glucose via fermentation.

Herein we report the first synthesis of a 3-deoxy-D-manno-octulosonic acid (KDO) building block starting from glucose through pathway engineering of Escherichia coli and subsequent chemical modifications to provide an alternative method to produce KDO, found in plant and bacterial oligosaccharides.

Insights into the Activation of Alkyne-Installed Glycosyl Donors with Dual Acidic Metal Catalysts: Reaction Pathway, Influencing Factors, and Enlightenment for Glycosylation.

The activation of alkyne-installed glycosyl donors with dual acidic metal catalysts were studied. Lewis and/or π acidity-activated pathways were observed for alkynyl carbonate-, ester-, and ether-type donors, and π acidity-promoted reaction mode afforded higher efficiency and yields. The activation mode for a certain metal catalyst is determined by the nature of catalysts itself, protecting groups on sugar rings, type of sugars, and structure of aglycones. The discovery gives us valuable insights into the glycosylation of alkyne-containing donors.

Ni(II)-Catalyzed Regio- and Stereoselective O-Alkylation for the Construction of 1,2-cis-Glycosidic Linkages.

A transition-metal-catalyzed O-alkylation for the regio- and stereoselective construction of 1,2-cis-glycosidic linkages is presented. With nonprecious and readily available Ni(II) as a catalyst, 1,2-cis-glycosides were obtained via O-alkylation of 1,2-carbohydrate diols that can be accessed in a small number of steps. The tedious design of protecting groups or anomeric leaving groups could be avoided with this method. The strategy was applied for the efficient preparation of an important commercialized glycosidic compatible solute GG, its derivative MGG, and a branched α-glucan.

Structurally Diverse Synthesis of Five-, Six-, and Seven-Membered Benzosultams through Electrochemical Cyclization.

We have developed a metal- and oxidant-free approach to structurally diverse synthesis of benzosultams from aryl sulfonamides through an electrochemical cyclization. Upon variation of the ortho substituent on aryl sulfonamides, five-, six-, and seven-membered benzosultams were efficiently assembled in an atom- and resource-economic manner. The generality of the process is demonstrated by the formation of five- to seven-membered cyclic products from 42 substrates bearing substituents with different electronic effects and steric hindrance.

Studies directed toward the synthesis of the massileunicellins. 2.

The fully substituted hydroisobenzofuran core of the massileunicellins containing 8 contiguous stereocenters was prepared in 12 steps from (S)-(+)-carvone. Noteworthy elements of the synthesis include a one-step oxidative rearrangement/epoxidation, a novel stereoselective directed reduction of a keto diol, and a directed hydrogenation of a congested tetrasubstituted alkene.

Fast and Low-Cost Purification Strategy for Oligosaccharide Synthesis Based on a Hop-On/Off Carrier.

A feasible and convenient strategy for oligosaccharide synthesis, which realizes reaction in solution while product purification occurs only by solid-liquid filtration, has been developed. By using a hop-on/off carrier (polytetrafluoroethylene particle), rapid synthesis of tumor-associated antigen Globo-H hexasaccharide has been successfully achieved within 5 steps in 48% overall yield without any intermediate purification by column chromatography. Also, global deprotection, including the cleavage of the tag, proceeded simultaneously only by one-step hydrogenolysis.

Tuning the Chemoselectivity of Silyl Protected Rhamnals by Temperature and Brønsted Acidity: Kinetically Controlled 1,2-Addition vs Thermodynamically Controlled Ferrier Rearrangement.

An acidity- and temperature-dependent chemoselective glycosylation of silyl-protected rhamnals with alcohols has been revealed. The reaction undergoes a 1,2-addition pathway with (±)-CSA as the catalyst at rt, affording kinetically controlled 2-deoxyl rhamnosides. In contrast, only thermodynamically controlled 2,3-unsaturated rhamnosides are formed via Ferrier rearrangement when elevating reaction temperature to 85 °C or using CF3SO3H instead. This tunable glycosylation allows facile and practical access to both 2-deoxyl and 2,3-unsaturated rhamnosides with excellent yields and high α-stereoselectivity.

Stereoselective ß-Mannosylation with 2,6-Lactone-bridged Thiomannosyl Donor by Remote Acyl Group Participation.

Stereoselective ß-mannosylation has been recognized as one of the greatest challenges of carbohydrate chemistry. Herein, we described a practical method for stereoselective construction of ß-mannosides by using a 2,6-lactone-bridged thiomannosyl donor through the remote acyl-group participation as well as the steric effect of O-4 substituent. The two effects are enabled through the conversion of a regular mannopyranosyl 4 C1 conformation into a 2,6-lactone bridged conformation. The lactone donor could be readily prepared in three steps on a gram scale and the ß-mannosylation proceeded smoothly with high stereoselectivity for primary, secondary and tertiary alcohol acceptors. In addition, this strategy was successfully applied to the synthesis of a naturally occurring trisaccharide.

n-Pentenyl-Type Glycosides for Catalytic Glycosylation and Their Application in Single-Catalyst One-Pot Oligosaccharide Assemblies.

We have developed a new type of n-pentenyl-type glycosides that can be activated by catalytic amounts of promoter, Hg(NTf2)2 or PPh3AuCl/AgNTf2, at room temperature. The mild activation conditions and outstanding stability of common protection/deprotection manipulations enable the enynyl donors to have broad applications in constructing various glycosidic bonds. Furthermore, under the Hg(NTf2)2-catalyzed conditions, the sequential activation of different types of donors was achieved, based on which a gentiotetrasaccharide was synthesized via the newly developed single-catalyst one-pot strategy.

Efficient Large Scale Syntheses of 3-Deoxy-D-manno-2-octulosonic acid (Kdo) and Its Derivatives.

An efficient method to rapidly synthesize 3-deoxy-D-manno-2-octulosonic acid (Kdo) and its derivatives in large scale has been developed. Starting from D-mannose, the di-O-isopropylidene derivative of Kdo ethyl ester was prepared in three steps on a scale of more than 40 g in one batch in an overall yield of 75-80% without any intermediate purification. Kdo, Kdo glycal, and 2-acetylated Kdo ester were synthesized quickly in high yield from a di-O-isopropylidene derivative of Kdo ethyl ester. 2-Deoxy-ß-Kdo ester was obtained with high stereoselectivity via the epimerization of the α-isomer using t-BuOH as a proton source.

Cycloaldol approach to the isobenzofuran core of eunicellin diterpenes.

[reaction: see text] A novel cycloaldol approach to the isobenzofuran core common to many of the eunicellin diterpenes is described. The cycloaldol precursor was prepared by aldol addition of (S)-(+)-carvone and methacrolein followed by etherification to a glycolate ester. Chemoselective enolization of the glycolate ester led to the cycloaldol adduct in high yield and diastereoselectivity. An oxidative rearrangement-allylic diazene rearrangement sequence established the requisite cis ring fusion.

[Studies on the synthesis and antitumor activity of the derivatives of cephalotaxine alkaloid esters].

AIM: To design and synthesize some cephalotaxine and drupacine derivatives with different substituentes on C3'-N of taxol side chain. METHODS: Protective side chain acid VI (4'S,5'R) was prepared from optically active (2'R,3'S) methyl beta-phenyl glycidate I in five steps. The desired acids were coupled with cephlotaxine and drupacine respectively in the presence of 2-DPC/DMAP, followed by acidic hydrolysis and acylating to give novel alkloid esters with different substitutes on C3'-N. RESULTS: The seven new esters were studied for antitumor activity, the results showed that the antitumor activity was influenced by the substituentes on C3'-N. CONCLUSION: It might provide some rational basis for further structral modification.