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[Display omitted] We describe a stereoselective synthesis of an optically active (1 R , 3aS, 5 R , 6 S , 7 aR)-octahydro-1,6-epoxy-isobenzo-furan-5-ol derivative. This stereochemically defined heterocycle serves as a high-affinity ligand for a variety of HIV-1 protease inhibitors. The key synthetic steps involve a highly enantioselective enzymatic desymmetrization of meso -1,2(dihydroxymethyl)cyclohex-4-ene and conversion of the resulting optically active alcohol to a methoxy hexahydroisobenzofuran derivative. A substrate controlled stereoselective dihydroxylation afforded syn -1,2-diols. Oxidation of diol provided the substituted 1,2-diketone and L-Selectride reduction provided the corresponding inverted syn -1,2-diols. Acid catalyzed cyclization furnished the ligand alcohol in optically active form. [ABSTRACT FROM AUTHOR]

Enantioselective syntheses of tert -butyl (( S )-2-(3,5-difluorophenyl)-1-(( S )-oxiran-2-yl)ethyl)carbamate and (( S )-2-(3,5-difluorophenyl)-1-(( R )-oxiran-2-yl)ethyl)carbamate are described. We utilized asymmetric syn- and anti- aldol reactions to set both stereogenic centers. We investigated ester-derived Ti-enolate aldol reactions as well as Evans’ diastereoselective syn -aldol reaction for these syntheses. We have converted optically active (( S )-2-(3,5-difluorophenyl)-1-(( S )-oxiran-2-yl)ethyl)carbamate to a potent β-secretase inhibitor. [ABSTRACT FROM AUTHOR]

An enantioselective synthesis of (3a S ,4 S ,7a R )-hexahydro-4 H -furo[2,3- b ]pyran-4-ol, a high-affinity nonpeptide ligand for a variety of potent HIV-1 protease inhibitors is described. The key steps involved a highly enantioselective enzymatic desymmetrization of meso -diacetate, an efficient transacetalization, and a highly diastereoselective reduction of a ketone. This route is amenable to large-scale synthesis using readily available starting materials. [ABSTRACT FROM AUTHOR]

An enantioselective synthesis of the C3–C21 segment of the novel immunosuppressant FR252921 is described. The C12 and C13 stereogenic centers were constructed by a non-aldol process utilizing optically active 4-phenylbutyrolactone. The C18 stereogenic center was installed using Braun’s highly diastereoselective acetate aldol reaction. Other key steps involved Curtius rearrangement and Horner–Wadsworth–Emmons olefination reactions. [ABSTRACT FROM AUTHOR]

[Display omitted] We describe a practical synthesis of optically active (3 S ,3 aR ,5 R ,7 aS ,8 S)-hexahydro-4 H -3,5-methanofuro[2,3- b ]pyran-8-ol. This stereochemically defined 6-5-5 tricyclic heterocycle is an important high-affinity P2 ligand for a variety of highly potent HIV-1 protease inhibitors that show clinical potential. The key steps involve an enantioselective ring opening of meso carbic anhydride mediated by the cinchona alkaloid. The resulting optically active acid was reduced to optically active bicyclo[2.2.1]hept-5-ene derivative which was converted to the ligand alcohol by ozonolysis, reduction, and dehydration of the resulting primary alcohol followed by ozonolytic cleavage and reduction. Optically active ligand alcohol was obtained in high enantiomeric purity (99 % ee). [ABSTRACT FROM AUTHOR]

Synthesis of novel HIV-1 protease inhibitors incorporating dioxatriquinane-derived P2-ligands is described. The tricyclic ligand alcohol contains five contiguous chiral centers. The ligand alcohols were prepared in optically active form by an enzymatic asymmetrization of mesodiacetate, cascade radical cyclization, and Lewis acid catalyzed reduction as the key steps. Inhibitors with dioxatriquinane-derived P2-ligands exhibited low nanomolar HIV-1 protease activity. [ABSTRACT FROM AUTHOR]

[Display omitted] Asymmetric aldol reactions of ester-derived titanium enolates of (R)-(N -tosyl)phenylalaninol propionate and bidentate aromatic aldehydes has been investigated. Substrate scope of this aldol reaction was examined with a variety of bidentate aromatic aldehydes to provide syn -aldol products with high diastereoselectivity and isolated yields. Both enantiomers of N -(tosyl)phenylalaninol are readily prepared from commercially available and optically active phenylalaninol. Mild saponification removed the chiral auxiliary and furnished optically active β-hydroxy carboxylic acids. [ABSTRACT FROM AUTHOR]

Aetheramides A and B are very potent anti-HIV agents. An enantioselective synthesis of a MEM-protected aetheramide A derivative is described. The synthesis was accomplished in a convergent and stereoselective manner. The key reactions involved asymmetric dihydroxylation, asymmetric allylation, asymmetric syn -aldol reactions, and asymmetric hydrogenation. [ABSTRACT FROM AUTHOR]

Catalytic FeCl3 in the presence of 4Å molecular sieves has been shown to effect highly diastereoselective tandem Prins and Friedel-Crafts cyclization of substituted (E/Z)-6-phenylhex-3-en-1-ol and a variety of aldehydes to provide a range of polycyclic compounds in good to excellent yields. The reaction of an enantioenriched alcohol with an aldehyde provided the cyclization product without loss of optical activity. Furthermore, a Lewis acid catalyzed ring opening resulted in functionalized tetralin derivatives with multiple chiral centers. [ABSTRACT FROM AUTHOR]

Abstract: Organocatalytic reactions of 3-olefinic oxindoles and pentane-1,5-dial were investigated to provide access to substituted spirocyclohexane oxindoles via Michael/aldol cascade reactions. Of particular interest, we have examined the stereochemical outcome of electron withdrawing and electron-donating groups on the oxindole ring nitrogen. Interestingly, we have observed that the N-protecting group on the oxindole has critical effect on aldol ring closure leading to ultimate stereochemical outcome of the hydroxyl center. The overall process is quite efficient and afforded products with multiple stereocenters in high yields and excellent enantioselectivities (>99% ee). [Copyright &y& Elsevier]

Abstract: Solid supported palladium(0) (SS-Pd) catalyzed highly chemoselective reduction of nitroarenes to the corresponding anilines was accomplished under a milder reaction condition. This catalyst showed high compatibility with various reducing agents (NaBH4, Et3SiH, and NH2NH2·H2O) and a large number of reducible functional groups such as sulfonamide, amides, carboxylic acid, ester, alcohol, halide, hetero cycle, nitrile, alkene, carbonyl, O-benzyl, and N-benzyl were tolerated. Most of the reactions were clean and high yielding. The SS-Pd catalyst could be recycled up to seven runs without significant loss of activity. [Copyright &y& Elsevier]

Abstract: In situ-generated (bis-DPPMB)–Cu(OTf)2 complex has been examined to catalyze a tandem olefin migration and Prins cyclization of an alkenol with various aldehydes. The reaction proceeded with electron-rich aromatic aldehydes at room temperature and provided functionalized tetrahydropyrans in good yields. An efficient synthesis of the bis-DPPMB ligand has also been described. [Copyright &y& Elsevier]

Abstract: A convenient optically active synthesis of (3aS,5R,6aR)-5-hydroxy-hexahydrocyclopenta[b]furan, a high-affinity nonpeptidyl ligand for HIV-1 protease inhibitor 2, is described. The synthesis utilizes commercially available (1R,5S)-(+)-2-oxabicyclo[3.3.0]oct-6-en-3-one as the starting material and oxymercuration or bromohydrin reaction as the key step. Enantiopure ligand was converted to protease inhibitor 2. [Copyright &y& Elsevier]

A chelation-controlled and highly diastereoselective synthesis of syn-aldols is described. Aldol reaction of (S)-valinol-derived ester with a variety of aldehydes proceeded with high syn-diastereoselectivities (up to 99:1) and isolated yields (94%). [Copyright &y& Elsevier]

A convenient protocol for amide bond formation for electron deficient amines and carboxylic acids is described. Amide coupling of aniline derivatives has been investigated with a number of reagents under a variety of reaction conditions. The use of 1 equivalent of EDC and 1 equivalent of DMAP, catalytic amount of HOBt and DIPEA provided the best results. This method is applicable for the synthesis of a range of functionalized amide derivatives with electron deficient and unreactive amines. [ABSTRACT FROM AUTHOR]

Abstract: Two new routes were established for the synthesis of biologically active natural product annomontine utilizing Pictet–Spengler and aza-Diels–Alder reactions as key steps. [Copyright &y& Elsevier]

Abstract: An enantioselective aza-Michael addition of indolines to α,β-unsaturated ketones was achieved using a bifunctional cinchona alkaloid-derived chiral squaramide derivative. Various β-indolinyl ketone derivatives were obtained in good to excellent yields and with high enantioselectivity. DDQ or MnO2 oxidation of indoline derivatives provided convenient access to various enantioenriched N-substituted indole derivatives. [Copyright &y& Elsevier]

Abstract: Oxidative activation of benzyl or cinnamyl ether bearing allylsilane derivatives using a catalytic amount of DDQ and 2equiv of CAN in the presence of PPTS provided functionalized 4-methylenetetrahydropyrans in good yields and excellent diastereoselectivity. The reaction could be applied to the synthesis of a variety of substituted tetrahydropyran derivatives. [Copyright &y& Elsevier]

Abstract: An efficient total synthesis of (+)-spisulosine (ES-285) was completed in nine steps from (S)-Garner’s aldehyde. The vicinal amino alcohol moiety with anti-configuration was achieved by a highly diastereoselective addition of vinyl magnesium bromide to Garner’s aldehyde. The long hydrocarbon chain of the antitumor natural product was installed via olefin cross metathesis of the benzyl-protected allylic alcohol with an appropriate olefin counterpart followed by hydrogenation. [Copyright &y& Elsevier]

Abstract: An efficient procedure for conversion of alcohols into the corresponding chlorides is described. Pivaloyl chloride/DMF complex is employed as a mild and inexpensive reagent. A possible reaction mechanism is proposed. [Copyright &y& Elsevier]

Abstract: A stereoselective synthesis of the C1–C12 segment of the potent cytotoxic macrolide, iriomoteolide 1a, has been accomplished. The key steps involve an enzymatic kinetic resolution of a β-hydroxy amide, a Pd-catalyzed cross-coupling to construct a substituted allylsilane, a highly and stereoselective conjugate addition of lithium dimethylcopper to an α,β-acetylenic ester and an elaboration of the C6–C7 trans-olefin geometry by a Julia-Kocienski olefination. [Copyright &y& Elsevier]

An asymmetric synthesis of the C10&z.sbnd;C24 fragment of the potent antitumor macrolide, peloruside A is described. All three stereogenic centers have been enantioselectively constructed utilizing Evans alkylation, Brown asymmetric allylboration, and a substrate controlled epoxide formation. Other key reactions involved Grubbs''s ring-closing olefin metathesis and Ando''s Z-selective olefination reaction. [Copyright &y& Elsevier]

A stereocontrolled synthesis of the C1&z.sbnd;C9 segment of the marine natural product peloruside A is described. The key steps involve Sharpless''s catalytic asymmetric dihydroxylation reaction, a chelation-controlled reduction of chiral β-alkoxy ketones to elaborate the syn-1,3-diol functionality and a ring-closing olefin metathesis of a homoallylic alcohol-derived acrylate ester to form an α,β-unsaturated δ-lactone. [Copyright &y& Elsevier]

Palladium catalyzed intramolecular aminoacetoxylation of d -ribose derived alkenyl tosylsulfonamide to deliver l -deoxyallonojirimycin in an overall yield of 19%. The preliminary screening of l -deoxyallonojirimycin against carbohydrate processing enzymes showed moderate inhibitory activity against α-glucosidase (yeast) and α-mannosidases. [ABSTRACT FROM AUTHOR]

Abstract: Solid supported palladium nano/microparticles were found to be active catalysts to perform mono- and β,β-double-Heck reactions. Different β-unsubstituted and substituted alkenes including acrylate, methacrylate, crotonate, styrene, acrylonitrile, and acrylamide were investigated successfully for mono- and β,β-double-Heck reactions with aryl iodide under milder reaction condition. One-pot β,β-double-Heck reaction of aryl iodides with α,β-unsaturated ester, amide, nitrile, and styrene derivatives were also performed under standard reaction conditions. Wide functional group tolerance, easy catalyst recovery, and recyclability up to twelve times without significant loss of catalytic activity added extra importance to the present process. [Copyright &y& Elsevier]

Abstract: Ligand-free solid-supported nano and microparticles of Pd(0) (SS-Pd) were used as a heterogeneous catalyst in carbon-heteroatom bond formation reactions. Nitro substituted aryl halides reacted with oxygen, sulfur, and nitrogen nucleophiles to afford the corresponding products in good yields. A one-pot sequential cross coupling and nitro-reduction was also performed using the same SS-Pd catalyst to access amine substituted carbon-heteroatomic molecules. In addition, SS-Pd could be recycled up to seven runs without a significant loss of catalytic activity. [Copyright &y& Elsevier]

Abstract: The synthesis of densely functionalized acyclic long chain terminal alkenic alcohols was achieved by reductive opening of glycal derived 2,3-epoxy-1-iodides, with commercial zinc dust alone in a short reaction time with excellent yields involving a simple reaction procedure and easy work-up. A mechanism involving an organometallic intermediate is proposed. [Copyright &y& Elsevier]

Abstract: Solid-supported nano and microparticles of Pd(0) (SS-Pd) were prepared and used as heterogeneous catalysts for Suzuki–Miyaura cross coupling reactions of aryl halides (chloro, bromo and iodo) and phenyl boronic acid under mild and ligand-free conditions. Scanning electron microscope (SEM) and UV–vis based studies were performed to observe the distribution of nano and microparticles of palladium over solid surface and their oxidation states. In addition, the catalyst could be reused up to seven runs without significant loss of activity and stable enough under moist conditions. [Copyright &y& Elsevier]

A self-associating synthetic tripeptide [Boc-Ala(1)-Aib(2)-β-Ala(3)-OMe (Aib: α-amino-isobutyric acid, β-Ala: β-alanine)] forms thermoreversible transparent gels in various organic solvents and this offers the first example of a peptide gelator whose molecular self-assembly afforded for gelation has been characterised by single-crystal X-ray diffraction and FT-IR and NMR spectroscopic studies. The crystal structure of an analogous synthetic non-gelator tripeptide [Boc-Ala(1)-Gly(2)-β-Ala(3)-OMe] is also discussed in light of the self-assembly of the gelator tripeptide. [Copyright &y& Elsevier]