Synthesis Of Benzyl Research Articles

Synthesis of regioselectively protected building blocks of benzyl β-d-glucopyranoside

Reported herein is the synthesis of benzyl β-d-glucopyranoside and its derivatives that provide straightforward access to 3,4-branched glycans. Modes to diversify the synthetic intermediates via introduction of various temporary protecting groups have been demonstrated.

Synthesis of benzyl chlorine‐free poly(4‐acetoxystyrene) via cationic polymerization followed by Friedel‐Crafts alkylation

The linear benzyl chlorine‐free poly(4‐acetoxystyrene) (PSTO) with low polydispersity (Mw/Mn = 1.3) is obtained through anisole quenching of the living polymerization of 4‐acetoxystyrene initiated with the St–Cl/SnCl4/n‐Bu4NBr system in CH2Cl2. The alkylation reaction rate increases with increasing anisole concentration and temperature. With a 4‐fold excess of anisole over the initiator, end‐chlorine groups are completely capped by anisole in 30 minutes at −15°C through adding extra SnCl4 prior to the alkylation reaction. In addition, by using 2‐methylanisole and 2,6‐dimethylanisole as capping agents, it is verified that both para‐ and ortho‐positions substitution of living PSTO cations to the anisole occur during alkylation reactions.

Synthesis of Benzyl C‐Analogues of Dapagliflozin as Potential SGLT2 Inhibitors

Sodium‐glucose co‐transporter (SGLT) inhibitors are a novel class of therapeutic agents for the treatment of type 2 diabetes based on blocking of renal reabsorption of glucose. Dapagliflozin, a C‐aryl glucoside, has emerged as a successful drug in the market based on this concept. We have synthesized hitherto unreported C‐benzyl glucoside analogues of Dapagliflozin carrying the same aglycon present in the drug. The synthetic strategy involves in situ generation of functionalized arylmagnesium bromide with Weinreb‐amide (WA) functionality for the first time, and addition on to the 1‐β‐formyl‐2,3,4,6‐tetra‐O‐benzyl‐D‐glucopyranoside for the synthesis of a C‐benzyl glucoside building block 16. The WA functionality therein enabled variation in the nature of the distal ring of biarylmethane aglycon for convenient access to other analogues. All the new compounds were screened for their sodium‐glucose co‐transporters (SGLT1 and SGLT2) inhibition activity using cell‐based nonradioactive fluorescence glucose uptake assay. Among them, 14 with IC50: 0.64 nm emerged as the most potent SGLT2 inhibitor with the best selectivity for inhibition of SGLT2 (IC50:0.64 nm) over SGLT1 (IC50: 500 nm) as compare to Dapagliflozin. On the other hand, compound 15a exhibited moderate selectivity for inhibition of SGLT2 (IC50: 4.94 nm) over SGLT1 (IC50: 68.46 nm). These results presented herein amply demonstrate the promise of C‐benzyl analogues of Dapagliflozin as novel SGLT2 inhibitors for future investigations.

Benzyl (R)-2-(Acetylthio)Propanoate: A Promising Sulfur Isoster of (R)-Lactic Acid and Ester Precursors

In this paper, an accessible chiral pool synthesis of benzyl (R)-2-(acetylthio)propanoate (acetylthiolactate), which is less odorous than the methyl or ethyl analogue, was performed through a clean SN2 displacement reaction using available AcSK with tris[2-(2-methoxyethoxy)]ethylamine (TDA-1), starting from commercially available benzyl (S)-lactate in 76%, 94% ee (2 steps). Deprotection of the acetyl group using N,N-dimethylethylenediamine afforded benzyl (R)-2-sulfanylpropanoate in 93% yield with 90% ee. These two sulfur-containing benzyl esters were sufficiently odorless to be purified by column chromatography. Direct HPLC analysis was applied to determine the enantiomeric excess without thiazolidin-4-one derivatizations. A complementary debenzylation of benzyl (R)-2-(acetylthio)propanoate was also performed using HBr/AcOH to afford (R)-2-(acetylthio)propanoic acid without critical racemization in 92% yield with 92% ee.

Design and synthesis of benzyl 4-O-lauroyl-α-L-rhamnopyranoside derivatives as antimicrobial agents

Design and synthesis of benzyl 4-O-lauroyl-α-L-rhamnopyranoside derivatives as antimicrobial agents

Synthesis of Benzyl Tetra-O-acetyl-α-L-glucopyranoside from Benzyl 2,3-Dideoxy-β-D-erythro-hex-2-enopyranoside

Synthesis of Benzyl Tetra-O-acetyl-α-L-glucopyranoside from Benzyl 2,3-Dideoxy-β-D-erythro-hex-2-enopyranoside

Synthesis of Orthogonally Protected Muramic Acid Building Blocks for Solid Phase Peptide Synthesis

Muramic acid is found in many peptide natural products containing oligo(poly)saccharide moieties. Taking into consideration that the Fmoc methodology is routinely used for solid-phase peptide synthesis, preparation of orthogonally protected muramic acid building blocks for total solid-phase synthesis of these natural products is of particular practical importance. Herein a simple and efficient synthesis of benzyl 2-amino-4, 6-O-benzylidene-3-O-[(R)-1-carboxyethyl]-2-deoxy-N-9-fluorenylmethyloxycarbonyl-α- D -glucopyranoside (6) from N-acetylglucosamine (1) is described. Important improvements over previous synthetic approaches to glucopyranosides 2 (benzyl 2-acetamido-2-deoxy-α- D -glucopyranoside) and 3 (benzyl 2-acetamido-4, 6-O-benzylidene-2-deoxy-α- D -glucopyranoside), key building blocks in preparation of 6, include synthesis simplification and efficient isolation and purification. Optically pure (S)-2-chloropropionic acid 7 was prepared and introduced to the positon 3-O of sugar moiety to give compound 4 (benzyl 2-acetamido-4, 6-O-benzylidene-3-O-[(R)-1-carboxyethyl]-2-deoxy-α- D -glucopyranoside) with the (R)-configuration of the lactyl side-chain in excellent overall yield and optical purity. Deacetylation of amino group gave compound 5 (benzyl 2-amino-4, 6-O-benzylidene-3-O-[(R)-1-carboxyethyl]-2-deoxy-α-D-glucopyranoside) suitable for incorporation of the Fmoc protecting group to give protected muramic acid derivative 6, a useful building block in peptide synthesis.

Synthesis of 2-deoxygalactopyranoside derivatives of benzyl alcohols with β-galactosidase from Aspergillus oryzae

The stereoselective synthesis of 2-deoxyglycosides is a challenge. Glycosidases are capable of catalyzing the synthesis of glycosidic linkages by the absolute stereoselectivity of the anomeric center. We report on an efficient stereoselective synthesis of benzyl β-D-2-deoxygalactopyranosides in the reaction of galactal with alcohols catalyzed using β-galactosidase from Aspergillus oryzae.

ChemInform Abstract: The Synthesis and Antiviral Properties of E-5-(2-Bromovinyl)-4′-thio-2′ -deoxyuridine.

A practical 7 step synthesis of benzyl 3,5-di-O-benzyl-2-deoxy-1,4-dithio-D-erythro-pentofuranoside from 2-deoxy-D-ribose is described and the product has been used in the synthesis of some 4′-thio-2′-deoxynucleosides which have potentially useful biological activity.

New Reagents for the Synthesis of Arylmethyl Ethers and Esters

This Account chronicles efforts leading up to the developmentof new arylmethyl transfer (benzylation) reagents for protectingoxygen functional groups under relatively mild and neutral conditions.It begins with an investigation of organosiletanes as surrogatehydroxyl groups, which inspired siletane-functionalized benzyl ethersand forced us to confront the difficulties associated with the synthesisof benzyl ethers. The end result is a new series of neutral oxypyridiniumsalts for the benzylation of various nucleophilic functional groupsunder mild conditions. 1 Introduction 2 Tamao-type Oxidation of Strained Organosiletanes 3 P-Siletanylbenzyl (PSB) ProtectingGroups 4 2-Benzyloxy-1-methylpyridinium Triflate 5 Friedel-Crafts Reactions and Mechanistic Insights 6 Benzyl Ester Formation 7 Substituted Benzyl Transfer Reagents 8 Conclusions and Outlook

Selective β-Hydroxyethylation at the N-1 Position of a Pyrazolone: Synthesis of Benzyl 1-(β-Hydroxyethyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylate

Selective 2-hydroxyethylation at the N-1 position of benzyl 5-methyl-3-oxo-2-phenyl-2,3-dihydro-1 H-pyrazole-4-carboxylate with epoxides was achieved using either AlMe 3 or Mg(ClO 4 ) 2 under mild conditions. The epoxide ring opening was both regioselective and stereospecific. Moderate to excellent yields were obtained from mono- and disubstituted epoxides with the exception of CIS-dimethyl-2-butene oxide that gave only a trace amount of the product.

Stereoselective synthesis of key intermediates for the preparation of strobilurins

The highly stereoselective synthesis of benzyl and tert -butyldimethylsilyl ethers of 3-methyl-6-arylhexa-3( Z ),5( E )-dienols, which are key intermediates in the syntheses of strobilurins A and X, has been developed.

Microwave‐Accelerated Synthesis of Benzyl 3,5‐Dimethyl‐pyrrole‐2‐carboxylate.

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Microwave‐accelerated synthesis of benzyl 3,5‐dimethyl‐pyrrole‐2‐carboxylate

Abstractmagnified imageBenzyl 3,5‐dimethyl‐pyrrole‐2‐carboxylate, a very useful pyrrole in porphyrin and dipyrromethene synthesis, can be synthesized via the Knorr‐type reaction, but in low yield. Alternative routes to benzyl 3,5‐dimethyl‐pyrrole‐2‐carboxylate have been developed involving the trans‐esterification of ethyl 3,5‐dimethyl‐pyrrole‐2‐carboxylate and the de‐acetylation of benzyl 4‐acetyl‐3,5‐dimethyl‐2‐carboxylate, both precursors being easily obtained using the Knorr reaction. These traditional methods involve treatment of the known products with a strong basic solution or heating for extended periods which often lead to decomposition. The use of microwave energy to promote these two reactions proves to be an extremely efficient way to obtain benzyl 3,5‐dimethyl‐pyrrole‐2‐carboxylate quickly, in high yield, and in excellent purity with no need for recrystallization. Of particular note is the use of catalytic sodium methoxide in benzyl alcohol, rather than stoichiometric amounts of sodium benzoxide, to effect benzylation.

Synthesis of benzyl- and benzhydrylferrocenes via Friedel–Crafts alkylation of ferrocene. Access to ferrocenyl bisphenols with high affinities for estrogen receptors

Ferrocene reacts with methoxy-substituted benzyl- and benzhydryl alcohols in the presence of trifluoroacetic acid to afford methoxybenzyl- or benzhydrylferrocenes in 47–56% yield. Demethylation of these compound leads to the ferrocenyl phenols and bisphenols. Some of the synthesized compounds display high affinity for estrogen receptors ERα and ERβ.

Parallel solution phase synthesis of benzyl (3S,4E)-4-[(arylamino)methylidene]-5-oxotetrahydrofuran-3-ylcarbamates

Benzyl (3S,4E)-4-[(dimethylamino)methylidene]-5-oxotetrahydrofuran-3-ylcarbamate 5 was prepared in 4 steps from L-aspartic acid 1. Acid-catalysed treatment of 5 with amines 6 gave the dimethylamine substitution products 7. Benzyl (3S,4E)-4-[(arylamino)methylidene]-5oxotetrahydrofuran-3-ylcarbamates 7c–n were prepared by parallel solution phase synthesis from 5 and anilines 6c–n in 45–94% yields. Enaminone 5 reacted with potassium cyanide in the presence of 18-crown-6 to afford benzyl 4-cyanomethyl-5-oxo-2,5-dihydrofuran-3-ylcarbamate 9. Upon reaction of 9 with nitrile oxide 10 the 1,2,4-oxadiazole derivative 11 was isolated in poor yield, while treatment of 9 with diazomethane 12 furnished the methylation products 13 and 14.

Phase Transfer Catalysis Method of Synthesis of Benzyl- and Benzhydryloxyalkoxyalkynes

The synthesis of benzyl- and benzhydryloxyalkoxyalkynes and the determination of the influence of phase transfer catalyst, solvent and temperature on this nucleophilic substitution reaction is reported.

A facile synthesis of benzyl α,β-unsaturated carboxylic esters

A simple, convenient and practical method is reported for the preparation of benzyl α,βunsaturated carboxylates using commercially available and inexpensive reagents under mild conditions.

Synthesis of benzyl O‐(2,3,3′‐tri‐O‐acetyl‐β‐D‐apiofuranosyl)‐(1→3)‐2,4‐di‐O‐benzoyl‐α‐D‐xylopyranoside and its X‐ray structure

AbstractThe protected apiose‐containing disaccharide, benzyl O‐(2,3, 3′‐tri‐O‐acetyl‐β‐D‐apiofuranosyl)‐(1→3)‐2, 4‐di‐O‐benzoyl‐α‐D‐xylopyranoside, was synthesized and its X‐ray structure provided.

Synthesis of Benzyl 4-Hydroxy-5-iodo-2,3-dimethoxy-6-methylbenzoate: The Aromatic Unit of Calicheamicin gamma1

Orsellinic acid (6) was benzylated, and the benzyl 4-benzyloxy-2-hydroxy-6-methylbenzoate (7) was then elaborated into the title compound (2), which is the aromatic constituent of calicheamicin gamma1I.