Mitsunobu Reaction Conditions Research Articles

Synthesis of Acyclic Nucleoside and Nucleotide Analogs Derived from 6-Amino-7H-purine-8(9H)-thione and 8-(Methylsulfanyl)adenine

Reaction of 8-bromoadenine derivatives1with thiourea in ethanol or butanol was used for the synthesis of the correspondingN9-substituted 6-amino-7H-purine-8(9H)-thiones2. 8-(Methylsulfanyl)adenine derivatives3were prepared by reaction of thiones2with iodomethane in 1 M sodium methoxide or in aqueous 1.5 M potassium hydroxide. Alkylation of 6-amino-7H-purine-8(9H)-thione (2a) proceeds preferentially on the sulfur atom. Under similar conditions, alkylation of 8-(methylsulfanyl)adenine (3a) with diverse alkylation agents affordedN9-substituted adenine derivatives3and6, andN3-substituted adenine derivatives5and7. 8,3'-S-Anhydro derivatives9were prepared in good yields by cyclization of 6-amino-7H-purine-8(9H)-thiones2dand2funder the Mitsunobu reaction conditions.

Regioselective N1-Alkylation of Guanosine Derivatives Protected at N 2 by an N,N-Dialkyl Amidine Group

Under Mitsunobu reaction conditions or in the presence of eiectrophilic alkylating reagents, alkylation of guanosine derivatives protected by an N,N-dialkyl amidine at the exocyclic amino group occurs selectively on nitrogen N 1 of the purine base.

Stereoselective Synthesis of Highly Functionalized Cyclopropanes. Application to the Asymmetric Synthesis of (1S,2S)-2,3-Methanoamino Acids.

One-pot palladium(0)-catalyzed alkylation and S(N)(') cyclization of 1,4-dichlorobut-2-ene 1 by the anion of alpha-substituted carbonitriles 2a-d can provide highly functionalized cyclopropanes (E)-4a-d, diastereoselectivity, (de 88-100%). Several attempts to achieve the asymmetric synthesis of the 1-amino-2-ethenylcyclopropanecarbonitrile (E)-9, by means of this new procedure, i.e., using chiral palladium ligands, chiral aminoacetonitriles (-)- and (+)-12 (from 1-hydroxypinanone) or chiral allyl chlorides (4S)-20b-d and (4R)-20e (from (2S) ethyl lactate) have pointed up the reversibility of the palladium-catalyzed cyclization step, responsible for the low enantioselectivity observed (ee </= 32%) and for the formation of byproducts, i.e., azepine derivatives 8a,b arising from subsequent aza Cope ring expansion. Molecular mechanics calculations using a modified MM2 type force field adapted to the pi-allyl palladium complexes have explained these results. However, when performed under the Mitsunobu reaction conditions (DEAD, PMe(3)), therefore, in the absence of palladium catalyst, the S(N)(') cyclization occurred also diastereoselectively (de > 88%) and provided the enantiomerically enriched 1-amino-2-propenylcyclopropanecarbonitrile (E)-22 (ee > 83%) suitable precursor of (1S,2S)-2,3-methanoamino acids.

Facile Synthesis of 8, 2′-S-Cyclopurine Nucleoside

This paper describes the synthesis of 8,2 -anhydro-8-mercapto-9-(β-D-arabinofuranosyl)purine (8,2′-S-cyclopurinenucleoside, 1) via the shorter route from 3′,5′-di-O-acectyl-8,2′-S-cycloadenosine (6) and by direct reductive deamination with n- pentyl nitrite in tetrahydrofuran (THF) and deacetylation. The preparation of 8,2′-S-cycloadenosine (2) was achieved in good yield by the cyclization of the protected 8-mercaptoadenosine with triphenylphosphine and diethyl azodicarboxylate (DEAD) in THF at room temperature, under Mitsunobu reaction conditions.

An Efficient Asymmetric Route to 2,3-Diaminobutanoic Acids

An Efficient Asymmetric Route to 2,3-Diaminobutanoic Acids

Applications of the Mitsunobu reaction in peptide chemistry.

The Mitsunobu reaction--the nucleophilic substitution of an alcoholic hydroxyl group mediated by the redox system trialkylphosphine/dialkyl azodicarobxylate--is widely used in the chemistry of biologically active compounds. The paper deals with applications of the Mitsunobu reaction in amino acid and peptide chemistry. The process provides easy access to many unnatural amino acids and derivatives. Since the reaction occurs with complete inversion of the configuration at the carbinol chiral centre, it can be used for the synthesis of diastereoisomers of hydroxy- and tioprolines. Cyclization of beta-hydroxy amino acid containing peptides under Mitsunobu reaction conditions leads to a constrained peptide that mimics the stabilizing reverse turn secondary structure.

ChemInform Abstract: Synthesis of Reversed Azole Nucleosides under the Mitsunobu Reaction Conditions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

AN IMPROVED SYNTHESIS OF 9-[2-(DIETHOXYPHOSPHONOMETHOXY)ETHYL]ADENINE AND ITS ANALOGUES WITH OTHER PURINE BASES UTILIZING THE MITSUNOBU REACTION

Abstract Unprotected adenine, 6-chloropurine, 2.6-diaminopurine. and 2-amino-6-chluropurine have been directly coupled with 2-(diethoxyphosphonomethoxy)ethanol under Mitsunobu reaction conditions to provide acyclic phosphonate nucleotide analogues which are intermediates for antiviral agents such as PMEA.

Enantioselective synthesis of 2-[5-(9 H-purin-9-yl)-2-cyclopenten-1-yl]-ethanol analogues as potential antiviral agents

The enantioselective synthesis of 2-[5-(9 H-purin-9-yl)-2-cyclopenten-1-yl]ethanol analogues is described. (1R,5R)-[1-( tert-butyldimethylsilyloxy)ethyl]-2-cyclopenten-5-ol 4a and (1S,5S)-[1-( tert-butyldimethylsilyloxy)ethyl]-2-cyclopenten-5-ol 4b were coupled with 6-chloropurine and 2-amino-6-chloropurine using Mitsunobu reaction conditions. Compounds 6a & b, 7a & b, 8a & b, 9a & b, and 10a & b were tested for antiviral activity.

Kinetic resolution of alcohols in an asymmetric mitsunobu reaction using chiral nonracemic 1,3,2-dioxaphosphepanes

Non-racemic chiral trivalent phosphorus derivatives 1 and 2 when employed under Mitsunobu reaction conditions, induce esterification between racemic alcohols and acids with moderate enantiospecificity (up to 39%). At the expense of high conversion, the alcohols can be obtained in high ee (> 99%).

Potential routes to flavan-3-ols, part 2: The Mitsunobu reactions of para-oxygenated benzylic alcohols

Under Mitsunobu reaction conditions para-methoxy benzylic give substantially racemic products, whereas para-pivaloyloxy and para-acetoxy benzylic alcohols give products resulting from inversion.

Synthesis of 2',3'-Dideoxy-3'-C-(hydroxymethyl)-4'-thionucleosides as Potential Inhibitors of HIV

The synthesis of 2',3'-dideoxy-3'-C-(hydrorymethyl)-4'-thionucleosides is described. For the synthesis of the carbohydrate part, the configuration of the secondary hydroxyl group in (2S,3R)-1-O-(p-bromobenzyl)-3-(2'-propenyl)-1,2,4-butanetriol (1) was inverted using Mitsunobu reaction conditions, after which the primary hydroxyl group in product 2 was regioselectively benzoylated using phase-traasfer catalysis. Oxidative cleavage of the allylic double bond, followed by ring closure and exchange of the p-bromobenzyl protecting group gave the methyl furanoside derivative 5, which was further converted to the corresponding dibenzyl dithioacetal 6

N-alkylation of indole ring using Mitsunobu reaction

Indole rings substituted with two electron withdrawing groups were alkylated on the nitrogen under Mitsunobu reaction conditions.

Synthesis of nucleoside analogues with a 1,5-anhydrohexitol moiety

Glucose after conversion to a 3-deoxy-1,5-anhydro-D-glucitol moiety, was coupled at its 2-position to heterocyclic bases either by nucleophilic displacement or under Mitsunobu reaction conditions to afford new nucleoside analogues with a 1,5-anhydrohexitol moiety.

The stereochemical outcome of the Mitsunobu reactions of para-oxygenated benzylic alcohols

Under Mitsunobu reaction conditions a para-methoxy benzylic alcohol gave substantially racemic products, whereas a para-pivaloyloxy and a para-acetoxy benzylic alcohol gave products resulting from inversion.

Convergent stereospecific total synthesis of monochiral Monocillin I related macrolides

The first total synthesis of Monocillin I related macrolides has been achieved by a convergent and stereospecific route involving the palladium - catalyzed coupling of a functionnalized chiral vinylstannane with the appropriate dimethoxy bromomethyl isocoumarin. Cleavage conditions of the isocoumarin ring were then found for the preparation of a precursor hydroxy acid. The 14-membered macrolide was obtained in the Mitsunobu reaction conditions, and the required natural conjugated dienone epoxide system of Monocillin I was generated stereospecifically from that macrocyclic precursor.

A general enantioselective synthesis of α-arylethylamines

Optically active α-arylethylamines were prepared starting from acetophenones in ≥95%ee and ≥70% overall yield using oxazaborolidine catalyzed enantioselective reduction followed by the displacement of the hydroxy group by an azide group with clean inversion under Mitsunobu reaction conditions.

The regioselective dehydration of unsymmetrical secondary alcohols under Mitsunobu's reaction conditions.

Dehydration of the four diastereomers of tetrahydropyran 8-11 involving the 4-hydroxyl and 5-methyl groups with diethylazodicarboxylate-PPh3-toluene was undertaken to clarify the relation between the configurations of these substituents and the direction of dehydration. Compound 8 with 4β(equatorial)-hydroxyl and 5β(axial)-methyl groups was found to give the trisubstituted olefin 12 exclusively, and the isomers 13 and 14 were shown to be produced from 9 and 11, respectively, with high selectivity. The mechanisms involved are discussed.

Regiospecific O-alkylation of δ-tetronic acids under mitsunobu-reaction conditions

An improved procedure for regiospecific O-alkylation of β-tetronic acids with primary and secondary alcohols, based upon Mitsunobu conditions, is presented. The reaction conditions are very mild and compatible with a variety of hydroxyl protecting groups such as MOM, tBuMe 2Si, isopropylidine and esters.

Simultaneous inversion of configuration of both the chiral ring and the carbinol carbon in (E)-(1 R,2R)-cyclo-oct-2-en-1-ol

The reaction of (–)-(E)-(1 R,2R)-cyclo-oct-2-en-1-ol with p-bromobenzoic acid under Mitsunobu reaction conditions yields the corresponding p-bromobenzoate with simultaneous inversion of configuration of both the chiral ring and the carbinol carbon.