Synthesis and Structure Determination of (2S, 2′S)-3-Phenyl-2-(pyrrolidin-2′-yl)- propionic Acid

Abstract

Aβ²,β³-homoproline derivative, (2S, 2′S)-3-phenyl-2-(pyrrolidin-2′-yl)propionic acid, was synthesized starting from l-proline. After preparation of the (4S, 4aS)-4-benzyl-4a,5,6,7-tetrahydro-pyrrolo-[1,2-c]pyrimidine-1,3-dione under a mild condition, the absolute configuration of target compound was assigned using 2D H-H COSY and H-H NOESY technologies.     

Asymmetric Synthesis of (-)-(2R,3R,6S)-Irnigaine

Introduction　　Asarelativelynewmemberofnaturalalkaloidswith2 ,6 disubstituted 3 piperidinolskeleton ,irnigaine 1wasisolatedfromthetubersofArisarumVulgare (Araceae)in1995byMelhaouiandBode .1Itsstructureandrelativeconfigurationswereelucidatedby1HNMRstudiesandtheabsoluteconfigurationwasproposedonthebasisofitsopti calrotation .1Soonafterthen ,Meyerandhisco workersreportedthefirstsynthesisof (- ) (2R ,3R ,6S) irni gaineandtheconfigurationconfirmation .Althoughtheirsynthesisroutewasshortan…     

Synthesis of 5-substituted-3-[(2′S,3′S)-3′-hydroxy-2′-hydroxymethyltetrahydrofuran-3′-yl]-1,2,4-oxadiazoles and their epimers

5-Phenyl-3-[(2′R,3′S)-3′-hydroxy-2′-dimethoxymethyltetrahydrofuran-3′-yl]-1,2,4-oxadiazole 10a and its epimer 11a, 5-methyl-3-[(2′R,3′S)-3′-hydroxy-2′-dimethoxymethyltetrahydrofuran-3′-yl]-1,2,4-oxadiazole 10b and its epimer 11b were synthesized from cyanohydrin benzoates 8a, 9a and cyanohydrin acetates 8b, 9b, respectively, by treatment with hydroxylamine in methanol via intramolecular transacylation and subsequent cyclization of the corresponding amidoximes. Hydrolysis and reduction of the dimethoxymethyl groups in the above compounds gave the desired compounds 12a, 13a, 12b and 13b.     

Synthesis of (1′S*,2R*,3R*)- and (1′S*,2R*,3S*)-N-arylsulfonyl-2-(1′-halogenethyl)-3-methylindolines and their selective toxicity against SH-SY5Y cell line

N-tosyl-2- and N-tosyl-4-halogen-substituted derivatives of 2-(1-methylbut-2-en-1-yl)aniline were synthesized and their molecular iodine-mediated cyclization was investigated. The cyclization upon interaction of N-tosyl-6-methyl-2-(1-methylbut-2-en-1-yl)aniline with molecular iodine in methyl tert-butyl ether or acetonitrile was studied, as well as the interaction of this sulfonamide with N-bromosucinimide in dichloromethane. Synthesized (2R*,3R*)- and (2R*,3S*)-N-arylsulfonyl-2-(1-halogenoethyl)-3-methylindoline derivatives showed cytotoxic activity against HEK293 cells, SH-SY5Y, Jurkat, and HepG2 cell lines. The compounds (2R*,3S*)-N-arylsulfonyl-7-bromo-2-(1-halogenoethyl)-3-methylindoline cis- 4a , stereoisomeric (2R*,3R*)-trans- 4h and (2R*,3S*)-N-tosyl-7-chloro-2-(1-halogenoethyl)-3-methylindoline cis- 4h demonstrated selective toxicity against SH-SY5Y cell line (IC₅₀ ≈ 3 ÷ 5 μM), and did not affect HEK293, Jurkat, and HepG2 cells.     

Synthesis and structural characterization of camphanates of (−)-(2S3S,3S) and (+)-(2S,3R)-4-Phenyl-3-bromo-2-butanol diastereoisomers

The X-ray crystal structures of (–)-syn-4-phenyl-3-bromo-2-butyl camphanate (I) and (+-anti-4-phenyl-3-bromo-2-butyl camphanate (II) have been determined. Thesyn diastereoisomer of bromohydrin has the (2S,3S) absolute configuration whereas theanti diastereoisomer has the (2S,3R) absolute configuration. The crystallized derivatives I and II have been obtained by the reaction of each stereoisomer of bromohydrin, synthesized by reduction with baker's yeast, with (1S)-camphanic chloride. Crystal data: (I) C₂₀H₂₅BrO₄:M _w: 409.32; orthorhombic,P2₁2₁2₁;a=11.245(3),b=12.086(1),c=14.512(4) å; Z=4; finalR=0.053 for 1819 observed reflections. (II) C₂₀H₂₅BrO₄;M _w=409.32; monoclinic, P2₁;a=11.352(1),b=6.378(1),c=14.255(2) å,=110.38(1);Z=2; finalR=0.045 for 1672 observed reflections.     

Synthesis of （S）-2-Ethoxy-3-Phenylpropanoic Acid Derivatives and Their Insulin-Sensitizing Activity

A series of （S）-2-ethoxy-3-phenylpropanoic acid derivatives were synthesized and their insulin-sensitizing activities were evaluated in 3T3-L1 cells. Compounds 1b, 1d, 1e and 1f exhibited more potent insulin-sensitizing activity than rosiglitazone.     

Asymmetric synthesis of heteroorganic analogs of natural products 5. Synthesis of pure diastereomers and enantiomers of fluoro-substituted (2S,3R)- and (2R,3R)-β-phenylserines

A convenient method is proposed for the preparative synthesis of pure diastereomers and enantiomers of fluoro-substituted (2S,3R)- and (2R,3R)--phenylserines by the hydroxyalkylation of the Ni(II) — complex of the Schiff base of glycine with (S)-2-N-(N¹-benzylpropyl)aminobenzophenone using the corresponding fluoro-substituted benzaldehydes.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya. No. 8, pp. 1906–1913, August, 1991.     

Synthesis and Anti-HIV Activity of Trisubstituted (3′R, 4′R)-3′,4′- Di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) Analogs

In our prior studies,3′,4′-di-O-(S)-camphanoyl-(+)-cis-khellactone(DCK,1,Figure1)and its derivatives including mono-and di-substituted DCK analogs were identified as a novel class of potent anti-HIV agents1-4.Because of its high potency and efficient syn-thesis,4-methyl-DCK25was chosen as a drug candidate for preclinical studies.How-ever,the low solubility and poor oral bioavailability of4-methyl-DCK limited its further development.Because high molecular hydrophobicity might be one re…     

Synthesis and crystal structure of Ni(II) complexes of 2′-(3,5-dibromo-2-hydroxybenzylidene)-3,5-dihydroxybenzoylhydrazide

A new mononuclear nickel(II) complex incorporating a Schiff-base ligand, [NiL₂](DMF)₄ (HL = 2′-(3,5-dibromo-2-hydroxybenzylidene)-3,5-dihydroxybenzoylhydrazide), has been synthesized and characterized by IR, UV-Vis, elemental analysis and X-ray crystal structure analysis. HL is an anionic tridentate ligand. The nickel atom is hexacoordinated with two oxygen atoms from keto group and two oxygen atoms from hydroxy group and two nitrogen atoms from amide, with the two nitrogen atoms occupying the axial positions forming a distorted octahedral coordination sphere.     

One-pot Synthesis and Crystal Structure of （1S,2R,3S,4R,5S）-1-Phenyl-2,4-dibenzoyl-3,5-difurylhexanol

(1S,2R,3S,4R,5S)-1-Phenyl-2,4-dibenzoyl-3,5-difurylhexanol 1 was synthesized by one-pot reaction of hypnone and furfurol in alkali H2O/EtOH solution and structurally defined to contain a chair-formed aliphatic carbocycle, on which the bulky substituents occupy the equatorial positions.     

Synthesis of (4R,5S)-(−)- and (4S,5S)-(+)-L-Factors and Muricatacin from D-Glucose

Abstract

In connection with our projects on the synthesis of biologically active 5-hydroxyalkan-4-olides which have a chiral 2.3-diol unit,¹ we have carried out the synthesis of (4R,5S)-(?)- and (4R,5S)-(+)-L-factors (1).² the proposed autoregulators from Streptomyees griseus, and muricatacin (2),³ a biologically active constituent from the seeds of Annona muricata L. via 2.3-dihydroxy aldehydes derived from D-glucose. Hex-3-enofuranose4 was prepared by the elimination of thetriflate derived from D-glucose.     

Synthesis and applications of (R)- and (S)-7,7′-dimethoxy-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene

The synthesis of (R)- and (S)-7,7′-dimethoxy-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene 5a and 5b is described. The phosphorus atoms in (S)-(−)-5b are shown to be slightly more basic than the phosphorus atoms in (S)-BINAP by comparing the magnitude of the ¹J (³¹P–⁷⁷Se) coupling constant in their respective diselenide derivatives. (S)-(−)-5b behaved similarly to (S)-BINAP in asymmetric Heck reactions.     

Synthesis of 2′(S), 3′(R),5′-trihydroxypentyladenine

A synthesis of 2′(S), 3′(R),5-trihydroxypentyladenine (1) from D-ribonic acid γ-lactone (2) is described.     

Synthesis of 2′-5′,3′-5′ linked triadenylates

2′-5′,3′-5′ Linked triadenylates have been synthesized by direct bisadenylylation of adenosine 2′ and 3′ hydroxyls with an adenosine 5′-phosphorochloridite followed by oxidation.     

Asymmetric Conjugate Addition of Alcohols to (R)-(-)-5-[(1R,2S,5R)-Menthyloxy]-2-(5H)-Furanone

(R)-(-y5-[(IR,2S,5R)-menthyloxy](1)isausefulchiralsynthonreadilypreparedonatWo-stepprocedure-l']FindingsoffuranoneringsexistingascomponentSofsomenaturalproductSI'laswellastheiractivereactivityl']havestimu1atedeXtensiveresearchofitSasymmetricreactionswhichincludeDiels-Alderreactions,l']l,3-dipo1arcycloadditions,['1Michaelauditionsl5]andconjugateedditionsofaminesl']andmercaPtans.g4:,::7f:7':theseadductsledtovariousmultifunctionalhomochiralbuildingblockssuchas2-alkyl-l,4-butanediols,I'l2-aI…     

Synthesis and biological activity of the (−)-(2R,3S,4S)-3-azido-4-methoxy-2-(1′S-methoxy-2′-azido)ethyl-thiolane

A stereospecific ring contraction reaction, promoted by NaN₃, was detected starting from a thiepane derivative obtained from d-sorbitol, an inexpensive alcohol sugar. The major polyfunctionalized thiolane derivative obtained was investigated as a potential glycosidase inhibitor.     

Enantioselective preparation of (2R,3R)-(+)- and (2S,3S)-(−)-2,3-epoxy-2-methylbutanoic acids and some derivatives

(2R,3R)-(+)- and (2S,3S)-(−)-2,3-epoxy-2-methylbutanoic acids (epoxyangelic acids) were prepared from (Z)-2-methyl-2-butenoic acid using the Sharpless asymmetric epoxidation method in combination with the use of (−)- and (+)-menthol as chiral auxiliaries. Both substances, obtained in high enantiomeric excess, were characterized by spectroscopic and optical activity data. Their absolute configuration was determined by correlation with (R)-(+)-2-methyl-1,2-butanediol.     

Synthesis,spectroscopic characterization,thermal, and photostability studies of 2-(2′-hydroxy-5′-phenyl)-5-aminobenzotriazole complexes

Three Mn(II), Co(II), and Cu(II) new transition metal complexes of the fluorescence dye: 2-(2′-hydroxy-5′-phenyl)-5-aminobenzotriazole/PBT derived from o-aminophenol and m-phenylenediamine have been synthesized. The structural interpretations were confirmed from elemental analyses, magnetic susceptibility and molar conductivity, as well as from mass, IR, UV–Vis spectral studies. From the analytical, spectroscopic, and thermal data, the stoichiometry of the mentioned complexes was found to be 1:2 (metal:ligand). The molar conductance data revealed that all the metal chelates are non-electrolytes and the chloride ions exist inside the coordination sphere. The thermal stabilities of these complexes were studied by thermogravimetric (TG/DTG) and the decomposition steps of these three complexes are investigated. The kinetic parameters such as the energy of activation (E*), pre-exponential factor (A), activation entropy (ΔS*), activation enthalpy (ΔH*), and free energy of activation (ΔG*) have been reported. Photostability of phenyl benzotriazole as fluorescence dye and their metal complexes doped in polymethyl methacrylate/PMMA were exposed to UV–Vis radiation and the change in the absorption spectra was achieved at different times during irradiation period.     

Synthesis of 2-(Substituted Benzylideneamino)-4-(4′-hydroxyphenyl) Thiazoles and Their O-Glucosides

2-Amino-4-(4′-hydroxyphenyl) thiazole 1a was prepared from reaction between p-hydroxyacetophenone, thiourea, and iodine; compound 1a was treated with several (aryl/hetro aryl) aldehydes to form 2-(substituted benzylideneamino)-4-(4′-hydroxyphenyl) thiazoles 2a–j, which were glucosylated by using acetobromoglucose as a glucosyl donor to afford 2-(substituted benzylideneamino)-4-(2, 3, 4, 6-tetera-o-acetyl-4′-o-β-d-glucosidoxyphenyl) thiazoles 3a–j, which further on during deacetylation produced 2-(substituted benzylideneamino)-4-(4′-o-β-d-glucosidoxyphenyl) thiazoles 4a–j. These compounds were evaluated for biological activity, and their structure was confirmed by IR, NMR, mass spectra, elemental, and chemical analysis.

     

Improved Resolution of (±)-cis-2′-Hydroxy-5,9-dimethyl-6, 7-benzomorphan and Preparation of Racemic, (+)-, and (-)-cis-2-Methylcyclopropyl-2′-hydroxy-5,9-dimethyl-6,7-benzomorphan (Cyclazocine)

We report novel procedures for the efficient resolution of (±)-cis-2 -hydroxy-5, 9-dimethyl-6, 7-benzomorphan via the (-)-N-acetyl-L-glutamate and (+)-α-bromocamphor-φ-sulfonate salts, the direct N-substitution of the (+)-α-bromocamphor-φ-sulfonate salts, and the use of these methods for the synthesis of racemic, (+)-, and (-)-cyclazocine.