Synthesis of (2S,4S)- and (2S,4R)-5-fluoroleucine and (2S,4S)-[5,5-2H2]-5-fluoroleucine

Syntheses of (2S,4S)- and (2S,4R)-5-fluoroleucine, and, and of (2S,4S)-[5,5-(2)H(2)]-5-fluoroleucine, have been completed. The methodology allows these compounds to be prepared in sufficient quantities for incorporation by solid-state protein synthesis into strategic sites in proteins for folding studies. X-ray structures of the epimers and have been obtained and show the presence of conformational isomerism. The torsion angles between the F-C bond and the main chain are compared with values found in a mutant of the protein ubiquitin in which (2S,4S)-5-fluoroleucine replaces leucine residues 50 and 67 in the native protein.     

The reaction of (4R,5R)- and (4S,5S)-4,5-epoxy-2(E)-hexenoates and secondary amines.

A reaction of methyl (4R,5R)-4,5-epoxy-2(E)-hexenoate 1 with N-benzylmethylamine gave a diastereomerically pure methyl (4R,5R)-4,5-epoxy-(3S)-N-benzylmethylamino hexanoate 6 and methyl (4S,5R)-4-N-benzyl-methylamino-5-hydroxy-2(E)-hexenoate 7. The former was chemoenzymatically converted to (-)-osmundalactone 11, which is an aglycone of osmundalin. On the other hand, the directly conjugated addition of dimethylamine to methyl (4S,5S)-4,5-epoxy-2(E)-hexenoate 1 followed by treatment with MeOH at 40 degrees C exclusively provided methyl (4R,5S)-4-dimethylamino-5-hydroxy-2(E)-hexenoate 16, which was converted into L-(-)-forosamine 18.     

Preparation of methyl (1R,2S,5S)- and (1S,2R,5R)-2-amino-5-tert-butyl-cyclopentane-1-carboxylates by parallel kinetic resolution of methyl (RS)-5-tert-butyl-cyclopentene-1-carboxylate

Comparison of the kinetic and parallel kinetic resolutions of methyl (RS)-5-tert-butyl-cyclopentene-1-carboxylate allows for the efficient synthesis of both (1R,2S,5S)- and (1S,2R,5R)-enantiomers of methyl 2-amino-5-tert-butyl-cyclopentane-1-carboxylate.     

(+)-(1S,2S,5R)-8-联苯薄荷醇的合成

以(R)-( )-pu legone为起始原料,经1,4-加成,还原两步反应合成了手性辅助试剂( )-(1S,2S,5R)-8-联苯薄荷醇及其差向异构体(-)-(1R,2S,5R)-8-联苯薄荷醇,总产率95%。其结构经1H NMR,13C NMR,IR,MS和X-射线衍射仪表征。     

Synthesis of (S,S)-1,5-bis(4-alkyl-5-hydroxy-2-oxo-3-azapentyl)-1,5-diazacyclooctane

Crown ether derivatives have been extensively developed to provide enhanced structural recognition of substrate alkyl-ammonium cations. In particular a number of investigations of complexation of chiral alkylammonium salts by chiral crown ethers have been reported. The enantioselectivity has been applied in the chromatographic resolution of amino acid perchlorates. In general the crown ethers used in these studies have been based upon derivatives of 2, 2′-dihydroxy-1, 1′-binaphthyl1 or deriv…     

手性双膦配体（4S,5S）—（—）—DIOP的合成

不对称催化是由潜手性反应物合成光活性化合物的有效途径,α,β-不饱和氨基酸的氢化立体选择性已达90％以上,L-Dopa的工业化生产则标志着不对称催化氢化开始走向实际应用。高选择性的催化剂一般是一价铑的手性双膦配体络合物,其中DIOP[2,3-O-异丙叉-     

Synthesis of (2S, 5S)-2,5-dimethoxyadipic acid

Conclusions (2S,5S)-Dimethoxyadipic acid was synthesized from the D-mannitol derivative.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2151–2153, September, 1974.     

Synthesis and modeling study of (2S,5R,6R)- and (2S,5R,6S)-6-hydroxy- 8-(1-decynyl)-benzolactam-V8 as protein kinase C modulators

[structures: see text] Both (2S,5R,6R)- and (2S,5R,6S)-6-hydroxy-8-(1-decynyl)benzolactam-V8 were designed and synthesized as PKC modulators. Biological assays reveal the (6R)-ligand to be 20-fold more potent than its (6S)-counterpart in binding to PKC alpha.     

A practical and improved synthesis of (3S,5S)-3-[(tert-butyloxycarbonyl)methyl]- 5-[(methanesulfonyloxy)methyl]-2- pyrrolidinone

A practical and improved synthesis of (3S,5S)-3-[(tert-butyloxycarbonyl)methyl]-5-[(methanesulfonyloxy)methyl]-2-pyrrolidinone (1) is described. The key transformations involve a highly efficient reaction sequence consisting of ethoxycarbonylation, alkylation, hydrolysis, and decarboxylation to produce compound 10. The process described herein is practical, robust, and cost-effective, and it has been successfully implemented in a pilot plant to produce a multikilogram quantity of mesylate 1.     

Pentasulfide S5(2-) as the first tridentate chelating ligand in Ru(P(OE)3)3S5(E = Me and Et)

Room temperature stirring of H2Ru(P(OE)3)4 (E = Me and Et) and elemental sulfur in benzene afforded the optically active compounds Ru(P(OMe)3)3S5 (1) and Ru(P(OEt)3)3S5 (2). Compounds 1 and 2 are crystallized in the trigonal space group P31 with a = 14.231(10) A, c = 10.24(1) A, V = 1794(2) A3, and Z = 3, and orthorhombic space group P212121 with a = 15.393(5) A, b = 18.126(6) A, c = 12.421(4) A, V = 3465(1) A3, and Z = 4, respectively. Solutions of 1 and 2 did not show any optical activity since the bulk materials are racemic mixtures. The X-ray analyses also reveal that in both compounds polysulfide S5(2-) ion acts as a novel tridentate ligand, resulting in an asymmetric bicyclic RuS5 unit having three- and five-membered rings around the ruthenium atom. Fragmentation of the S5(2-) ring to S2- ion was observed in the presence of sulfur-abstracting reagents such as PR3 (R = Ph, OMe, and OEt) and also to S2(2-) ion when the compounds were reacted with RuCl2(P(OE)3)4 (E = Me and Et).     

Stereocontrolled Syntheses of (4S, 5R)- and (4S, 5S)-Dihydroxy-N-Decanoic Acid-4-Lactones Via Biochemical Methods

(4S-5R)- and (4S-5S)-dihydroxy-n-decanoic acid-4-lactones have been synthesized in a stereocontrolled manner by a chemomicrobiological approach.     

New Chiral Diamines of the Dioxolane Series: (+)-(4S,5S)-2,2-Dimethyl-4,5-bis(diphenylaminomethyl)- 1,3-dioxolane and (+)-(4S,5S)-2,2-Dimethyl-4,5-bis(methyl- aminomethyl)-1,3-dioxolane

The reaction of sodium diphenylamide with 2,2-dimethyl-4,5-bis(tosyloxymethyl)-1,3-dioxolane gave (+)-(4S,5S)-2,2-dimethyl-4,5-bis(diphenylaminomethyl)-1,3-dioxolane, which was brought into complex formation with cobalt chloride. Treatment of 2,2-dimethyl-4,5-bis(tosyloxymethyl)-1,3-dioxolane with sodium N-methylanilide resulted in cleavage of the SÄO bond in the p-toluenesulfonate moiety with formation of N-methyl-N-phenyl-p-toluenesulfonamide and 4,5-bis(hydroxymethyl)-2,2-dimethyl-1,3-dioxolane disodium salt. Diethyl (4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-dicarboxylate reacted with methylamine to give the corresponding dicarboxamide which was reduced with lithium aluminum hydride to (4S,5S)-2,2-dimethyl-4,5-bis(methylaminomethyl)-1,3-dioxolane having chiral carbon and nitrogen atoms.     

Combinatorial solution-phase synthesis of (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxamides

Solution-phase combinatorial synthesis of (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxamides was studied. First, di-tert-butyl (2S,4S)-4-amino-5-oxopyrrolidine-1,2-dicarboxylate hydrochloride was prepared as the key intermediate in five steps from (S)-pyroglutamic acid. Acylation of the amino group followed by acidolytic deprotection gave (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxylic acids, which were then coupled with amines to furnish a library of (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxamides. Four coupling reagents, BPC, EEDQ, TBTU, and PFTU, were tested for the amidation reactions in the final step. Amidations with EEDQ and TBTU led to the desired carboxamides. On the other hand, BPC and PFTU were not suited, since diketopiperazines were sometimes obtained instead of the desired carboxamides.     

Total synthesis of (S)-(+)-curcudiol, and (S)-(+)- and (R)-(-)-curcuphenol.

A highly enantioselective synthesis of the versatile chiral synthons possessing one stereogenic center, (S)- and (R)-4-aryl-5-hydroxy-(2E)-pentenoate (3) was achieved based on the enzymatic reaction of (+/-)-3 with commercially available lipases MY-30 or OF-360 from Candida rugosa. Application of (S)-3 and (R)-3 to the total syntheses of(S)-curcuphenol (1), (S)-curcudiol (2), and (R)-curcuphenol (1), respectively, is described.     

Novel bicyclic nucleoside analogue (1S,5S,6S)-6- hydroxy-5-hydroxymethyl-1-(uracil-1-yl)-3,8-dioxabicyclo[3.2.1]octane: synthesis and incorporation into oligodeoxynucleotides

The novel bicyclic nucleoside (1S,5S,6S)-6-hydroxy-5-hydroxymethyl-1-(uracil-1-yl)-3,8-dioxabicyclo[3.2.1]octane [2'-deoxy-1'-C,4'-C-(2-oxapropano)uridine] (15), expected to be restricted into an O4'-endo furanose conformation, was synthesized from the known 1-(3'-deoxy-beta-D-psicofuranosyl)uracil 5. The phosphoramidite derivative of 15 was successfully incorporated into oligodeoxynucleotides using standard methods, and thermal denaturation studies showed moderate decreases in duplex stabilities of -2.1 and -1.5 degrees C per modification toward complementary DNA and RNA, respectively.     

An asymmetric synthesis of (2S,5S)-5-substituted azepane-2-carboxylate derivatives

To facilitate a drug discovery project, we needed to develop a robust asymmetric synthesis of (2S,5S)-5-substituted-azepane-2-carboxylate derivatives. Two key requirements for the synthesis were flexibility for elaboration at C5 and suitability for large scale preparation. To this end we have successfully developed a scalable asymmetric synthesis of these derivatives that starts with known hydroxy-ketone 8. The key step features an oxidative cleavage of aza-bicyclo[3.2.2]nonene 14, which simultaneously generates the C2 and C5 substituents in a stereoselective manner.     

Totally selective synthesis of enantiopure (3S,5S)- and (3R,5R)-4-amino-3,5-dihydroxypiperidines from aminodiepoxides derived from serine

The transformation of enantiopure (2R,4R)- and (2S,4S)-N,N-dibenzyl-1,2:4,5-diepoxypentan-3-amine, 1 and 2, into the corresponding enantiopure (3S,5S)- and (3R,5R)-3,5-dihydroxy-3-aminopiperidines, 3 and 4 respectively, is described. The opening of the two epoxide rings with a range of amines takes place with total regioselectivity and high yields, in the presence of LiClO4. A mechanism to explain this transformation is proposed.     

5-(S)-孟氧基-3,4-二卤-2(5H)-呋喃酮与4-硝基邻苯二胺的Michael加成―消除反应

在Et3N作为碱的温和条件下,5-(S)-孟氧基-3,4-二卤-2(5H)-呋喃酮与芳香胺4-硝基邻苯二胺发生串联的Michael加成―消除反应,生成了新的含有苯环结构的5-孟氧基-4-氨基-3-卤-2(5H)-呋喃酮类化合物。新化合物的结构通过紫外―可见光谱(UV-Vis)、红外光谱(IR)、质谱(MS)、核磁共振氢谱(1H NMR)、核磁共振碳谱(13C NMR)和元素分析等表征证实。该多环结构卤代2(5H)-呋喃酮化合物的合成,能为某些多官能团的结构复杂的2(5H)-呋喃酮化合物的合成提供新途径。     

A Convenient Approach to the Enantiopure (1S,2S,4S,5S)-and (1R,2S,4R,5S)-2,5-Bis(phenylmethyl)-1,4-diazabicyclo[2.2.2]-octane

Introduction1,4 Diazabicyclo[2 .2 .2 ]octane (DABCO)wasre portedtocatalyzeorganicreactionsduetoitsstrongbasici ty .1,2 Severalchiraltrans 2 ,3 disubstitutedDABCOshavebeensynthesizedandappliedtotheasymmetricBaylis Hillmanreaction3andvicinalhydroxylation .4ThefirstsynthesisofthetitlecompoundwasreportedbySoai5from (2S ,5S) bis(phenylmethyl)piperazine (1) ,asshowninScheme 1.Butthisprocedureislengthy ,andtheoverallyieldisnotsosatisfactory .Besides ,thereport edmethodforthepreparationof 1is…     

Stereoselective synthesis of the nonproteinogenic amino acid (2S,3R)-3-amino-2-hydroxydecanoic acid from (4S,5S)-4-formyl-5-vinyl-2-oxazolidinone

(4S,5S)-4-Formyl-5-vinyl-2-oxazolidinone (4b), which is readily obtained via a zinc-silver-mediated reductive elimination of alpha-d-lyxofuranosyl phenyl sulfone (3b), is successfully converted to the naturally occurring, nonproteinogenic amino acid (2S,3R)-3-amino-2-hydroxydecanoic acid (2). Also in this study, a facile "oxazolidinone rearrangement" reaction is uncovered during the attempted formation of the (methylthio)thiocarbonate derivative of the oxazolidinone alcohol 7.