Environmentally Benign Synthesis of Sugar Orthoesters Promoted by Anhydrous Sodium Acetate and Ultrasound

A convenient and alternative procedure for the synthesis of sugar orthoesters from glycosyl bromides with anhydrous sodium acetate as base under ultrasound irradiation is described. Various sugar and sugar‐sugar orthoesters were prepared in 70%–91% isolated yields.     

2-DICHLOROMETHYL-1,3-DIOXOLAN-2-YL ORTHOESTERS. A POTENTIAL PROTECTING GROUP FOR SUGAR DERIVATIVES

Reactions of 2-dichloromethylene-1,3-dioxolane (2) with acetal protected sugar derivatives in neutral media gave 2-dichloromethyl-1,3-dioxolan-2-yl orthoesters. These orthoesters are readily hydrolysed under mild acidic conditions offering a new method for the preparation of readily removable protecting groups. This strategy was realised in the preparation of 6-O-acetyl-3,5-di-O-methyl-1,2-O-isopropylidene-α-d-glucofuranose.     

Polyhydroxylated homoazepanes and 1-deoxy-homonojirimycin analogues: Synthesis and glycosidase inhibition study

The Johnson-Claisen rearrangement of D-gluco and L-ido-derived allylic orthoesters afforded gamma,delta-unsaturated ester that on ester reduction, epoxidation, regioselective oxirane opening by sodium azide and hydrogenation led to sugar amino alcohols--immediate precursors for 1-deoxy-homonojirimycin 3a,b, and polyhydroxylated homoazepanes 4a,b. Our synthetic approach and glycosidase inhibitory activity is reported.     

Communication: Synthesis of 3-O-Benzyl-β-L-Arabinofuranose 1,2,5-Orthopivalate as a Starting Monomer for Ring-Opening Polymerization

We have studied the ring-opening polymerizations of a variety of glucose orthoester derivatives and found that substituents on the monomer play an important role in stereo- and regioregularity of the resulting polymers.^1-3 These substituent effects open the possibility of application to ring-opening polymerizations of other sugar orthoesters to give stereo- and regioregular polysaccharides. Additionally, the ring-opening polymerization of the galactose orthoester derivative⁴ gave stereoregular (1→5)-β-D-galactofuranan.     

Efficient chemical synthesis of a dodecasaccharidyl lipomannan component of mycobacterial lipoarabinomannan

Lipomannan (LM) is one of the domains of lipoarabinomannan (LAM) glycolipids, the latter being one of several cell surface organic molecules that fortify mycobacterial species against external attack. Some members of mycobacterial families are pathogenic, most notably Mycobacterium tuberculosis and Mycobacterium leprae, while others are nonpathogenic, and used in the clinic, such as Mycobacterium smegmatis. Additional biological significance arises from the fact that LM has been implicated in several health disorders outside of those associated with mycobacterial pathogens, notably for treatment of bladder cancer. LM is comprised of a heavily lipidated phosphoinositide dimannoside headgroup, from which a mannan array, of varied complexity, extends. The latter consists of a 1,6-alpha-linked backbone flanked at position O2, not necessarily regularly, with alpha-linked mannosides. This paper gives an example of lipomannan synthesis in which all of the sugar components, whether functioning as donors or acceptors, are obtained from n-pentenyl orthoesters, themselves in turn prepared in three easy steps from D-mannose. Assembly of the mannan array is facilitated by the exquisite regioselectivity occasioned by the use of ytterbium triflate/N-iodosuccinimide as the trigger for reaction of n-pentenyl orthoesters.     

Reaction of cholesterol with acetylated alkyl orthoacetates of D-glucopyranose

Summary The condensation of acetylated alkyl orthoacetates of D-glucose with cholesterol has been studied. It has been shown that either transesterification or glycosylation may take place, according to the reaction conditions. Conditions have been found under which the sole direction of the reaction is glycosylation, leading to the 1, 2-trans-glycoside. A standard method for glycosylating complex alcohols with sugar orthoesters has been proposed.Khimiya Prirodnykh Soedinenii, Vol. 2, No. 1, pp. 6–12, 1966     

Total synthesis of everninomicin 13,384-1--Part 4: explorations of methodology; stereocontrolled synthesis of 1,1'-disaccharides, 1,2-seleno migrations in carbohydrates, and solution- and solid-phase synthesis of 2-deoxy glycosides and orthoesters

Methods for the stereocontrolled construction of 1,1'-disaccharides, 2-deoxy glycosides, and orthoesters are reported. Specifically, a tin-acetal moiety was utilized to fix the anomeric stereochemistry of a carbohydrate acceptor leading to an efficient and stereoselective synthesis of 1,1'-disaccharides, while a newly discovered 1,2-phenylseleno migration reaction in carbohydrates opened entries to 2-deoxy glycosides and orthoesters. Thus, reaction of 2-hydroxy phenylselenoglycosides with DAST led to 2-phenylselenoglycosyl fluorides which reacted with carbohydrate acceptors to afford, stereoselectively, 2-phenylselenoglycosides. The latter compounds could be reductively deselenated to 2-deoxy glycosides or oxidatively converted to orthoesters via the corresponding ketene acetals.     

Copper-catalyzed 1,4-protosilylation and 1,4-protoborylation of enynic orthoesters for synthesis of functionalized 2,3-allenoates

Herein, copper-catalyzed 1,4-protosilylation and 1,4-protoborylation of enynic orthoesters have been developed. The enynic orthoesters as precursors of unstable enynic esters were applied to produce the functionalized 2,3-allenoate products. Meanwhile, the asymmetric 1,4-protosilylation of enynic orthoesters with Ph Me2Si-Bpin was also studied. The chiral monopyridine imidazoline ligand was efficient to provide the asymmetric 1,4-protosilylation products with high enantioselectivity.     

Bisorthoesters as polymer intermediates. II. A facile method for the preparation of polybenzimidazoles

Aromatic bisorthoesters were found to be good polymer intermediates and could be condensed with aromatic tetramines under mild conditions, in DMSO at 100°C in a relatively short reaction time to give polybenzimidazoles. The hexapropyl orthoesters of terephthalic and isophthalic acid were the preferred aromatic orthoesters because they were relatively easily purified by vacuum distillation to polymer grade intermediates, since they are liquids. Higher orthoesters distill even under good vacuum near or above the decomposition temperature of the orthoester group. Hexaethyl orthooxalate was also used and is a very useful and stable derivative of oxalic acid, which can be used for condensation reactions. These three orthoesters were used for condensations with 3,3′,4,4′-tetraaminobiphenyl, 1,2,3,4-tetraaminobenzene, 3,3′,4,4′-tetraaminobiphenyl ether, and 3,3′,4,4′-tetraaminobenzophenone. All polybenzimidazoles were obtained in high to quantitative yields and with varying molecular weights (η_inh = 0.1?0.8 dl/g), which in some cases were in the fiber forming range.     

An efficient synthesis of 2,6-disubstituted benzobisoxazoles: new building blocks for organic semiconductors

2,6-Disubstituted benzobisoxazoles have been synthesized by a highly efficient reaction of diaminobenzene diols with various orthoesters. The scope of this new reaction for the synthesis of substituted benzobisoxazoles has been investigated using four different orthoesters. The utility of these compounds as building blocks for the synthesis of conjugated polymers is demonstrated.     

Carbon-carbon bond formation by ‘double activation’. The synthesis of piperolide and fadyenolide intermediates.

Buenolide anions do not react with orthoesters and butenolides do not react with carbocations derived from acetals and orthoesters. However double activation of the butenolide (as the carbanion) and the alkoxyalkanes (as the stabilised carbocations) leads to high yield carbon-carbon bond formation of some generality.     

Formation of Orthoesters of Oleanolic Acid During Königs-Knorr Glycosidations

Summary.  The formation of orthoesters during K?nigs-Knorr reactions is described. Diphenylmethyl oleanolate reacts with 1 → 4 linked disaccharide donors to orthoesters instead of the expected glycosides. The reaction with acetobromoglucose gave a mixture of orthoester and glycoside. The influence of the structure of the glycosyl donors and of the reaction conditions on the formation of orthoesters is discussed. Received February 12, 2001. Accepted February 22, 2001     

A selective and convenient ruthenium mediated method for the synthesis of mixed acetals and orthoesters

Addition of alcohols and phenols to O-allyl compounds (allyl ethers and acrolein acetals), catalyzed by [RuCl₂(PPh₃)₃], was examined. Intramolecular addition of an OH group, leading to the formation of cyclic acetals and orthoesters, was also investigated. As a result, a new, selective and convenient method for the synthesis of symmetrical and unsymmetrical (mixed) acetals and orthoesters was developed.     

A facile and efficient synthesis of enyne-reaction precursors by multicomponent reactions

Using improved reaction protocols for three-component coupling reactions of aldehydes, dienophiles, and amides (AAD-reaction) or anhydrides (ANAD-reaction) or orthoesters (ALAD-reaction), a variety of functionalized hexahydroisoindolo derivatives were synthesized and fully characterized. Condensation of ubiquitous available aldehydes with unsaturated amides or anhydrides or orthoesters and subsequent Diels-Alder reactions with electron deficient dienophiles furnishes endo-selective enyne-reaction precursors in good to excellent yield.     

Mechanistic studies of the biomimetic epoxy ester-orthoester and orthoester-cyclic ether rearrangements

The relative rates of acid-catalyzed rearrangements of epoxy esters to [3.2.1]bicyclic orthoesters, the subsequent rearrangements of these ortho esters to substituted tetrahydrofurans, and the rates of orthoester hydrolysis at pH 4.75 were measured in NMR kinetics experiments. The ease of formation and stabilities of these orthoesters compared favorably with the OBO-type [2.2.2]bicyclic orthoesters typically used as protecting groups of carboxylic acids. Studies with 13C NMR-detected 18O-labeling show that epoxy ester rearrangement takes place preferentially via 6-exo cyclization, although the 7-endo process competes when the distal center of the epoxide is disubstituted. The ortho ester-cyclic ether rearrangement was shown by 18O-labeling to occur exclusively via intermediacy of a five-membered dioxonium ion. The structures of the hydrolysis products also indicate the intermediacy of a dioxolanium ion during hydrolysis. The implications for a hypothetical biosynthesis of marine polyether toxins are discussed.     

Anomalous behavior of 1,2-tert-butylorthoacetyl-3,4,6-tri-O-acetyl-α-D-glucopyranose dueing glycosylation in nitromethane catalyzed by mercuric bromide

Conclusions The condensation of the orthoesters of sugars, containing a sterically hindered alkoxyl group (for example, tert-butoxyl), with alcohols is not catalyzed by mercuric bromide, but only by proton donors, in contrast to the reactions of the simpler homologs of orthoesters.See [1] for preceding communication.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12, pp. 2793–2794, December, 1971.     

Efficient synthesis of 1,3,4-oxadiazoles promoted by NH4Cl

An efficient and inexpensive approach to the synthesis of 2-substituted and 2,5-disubstituted 1,3,4-oxadiazoles from arylhydrazides and orthoesters is reported using catalytic NH₄Cl. The conditions are mild, and thus, compatible with a variety of functional groups. The optimized reaction is performed using 30 mol % of NH₄Cl in 100% EtOH and is generally complete within 1 h for non-aromatic orthoesters and 2–10 h for aromatic orthoesters. The reaction permits both electron-releasing and electron-withdrawing groups on the arylhydrazide substrate. Most products are formed in high yields and require only minimal purification. Compared with earlier reports, the current reactions proceed in shorter time and require less of the orthoester.     

Determination of orthoesters by hydrolysis and Karl Fischer titrimetry

The acid hydrolysis of orthoesters has been made the basis of a titrimetric method. The method involves reaction of an orthoester with a known excess of water in a trichloroacetic acid-methyl alcohol system, followed by determination of unreacted water by Karl Fischer titration.     

Über die Herstellung des Methyl-α-D-fructopyranosides und die Struktur der dabei gebildeten Orthoester

Concerning the preparation of methyl α-D -fructopyranoside and the structure of the orthoester by-products Koenigs-Knorr glycosidation (AgClO₄/Ag₂CO₃) of the easily accessible p-nitrobenzoylated fructosylchloride 7 yields mainly the protected glycoside 3 which was deacylated to the known title compound 1 . The orthoesters 15 and 16 were formed as by-products in this glycosidation whilst the analogous orthoesters 21 and 22 are formed as main products in the glycosidation (Ag₂CO₃) of the benzoylated fructosylchloride 12 . The structure of these orthoesters was deduced mainly from their spectroscopic data, from those of their derivatives 17 , 18 , 19 , 20 , 25 and 26 and by comparison of the latter with the model compounds 31 and 34 .     

Functionalized orthoesters as powerful building blocks for the efficient preparation of heteroaromatic bicycles

By combining substituted anilines with functionalized orthoesters, an efficient and connective methodology for the preparation of benzoxazole, benzothiazole, and benzimidazole derivatives has been established. The versatility of this approach enables the development of new libraries of heterocycles containing multifunctional sites.