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.     

Stereospecific radical addition of isopropanol andn-butanal to (5R)-(l-menthyloxy)furan-2(5H)-one

The radical addition of PrⁱOH andn-butanal to (5R)-5-(l-menthyloxy)furan-2(5H)-one occurs regio- and diastereospecifically at position 4 of the furanone ring.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 345–536, March, 1995.This work was carried out with the financial support of the Russian Foundation for Basic Research (Project No. 93-03-04497).     

Syntheses of (R) [4-2H2] 2-Amino-3-Butenoic Acid (Vinylglycine) and (R) [4-2H2, 5-2H3] Methionine

Treatment of (R) methionine sulfoxide with NaOD led to exchange of the C-4 methylene and C-5 methyl protons; exchange of the chiral C-2 proton did not occur. Reducation with mercaptoacetic acid gave (R)-[4-²H₂, 5-²H₃] methionine. The latter was converted into its carbobenzyloxy methyl ester sulfoxide, pyrolysis of which followed by deprotection yielded (R)-[4-²H₂] vinylglcine as the hydrochloride.     

Synthesis of (2S,3S)-[3-(2)H1]-4-methyleneglutamic acid and (2S,3R)-[2,3-(2)H2]-4-methyleneglutamic acid

(2S,3S)-[3-(2)H1]-4-Methyleneglutamic acid 1a and (2S,3R)-[2,3-(2)H2]-4-methyleneglutamic acid 1b have been synthesised for use in biosynthetic and metabolic studies.     

Asymmetric conjugate reductions with samarium diiodide: asymmetric synthesis of (2S,3R)- and (2S,3S)-[2-2H,3-2H]-leucine-(S)-phenylalanine dipeptides and (2S,3R)-[2-(2)H,3-2H]-phenylalanine methyl ester

The highly diastereoselective samarium diiodide and D(2)O-promoted conjugate reduction of homochiral (E)- and (Z)-benzylidene and isobutylidene diketopiperazines (E)-5,7 and (Z)-6,8 has been demonstrated. This methodology allows the asymmetric synthesis of methyl (2S,3R)-dideuteriophenylalanine 27 in > or = 95% de and >98% ee, and (2S,3R)- or (2S,3S)-dideuterioleucine-(S)-phenylalanine dipeptides 37 and 38 in moderate de, 66% and 74% respectively. A mechanism is proposed to account for this process.     

(3R,11aR)-3-Phenyl-2,3,11,11a-tetrahydro-[1,3]oxazolo[3,2-b]-[2]benzazepin-5(10H)-one as a chiral building block for the asymmetric synthesis of 3-substituted 2-benzazepines

A five-step synthesis of the chiral building block cis-2 is described. Key steps in the synthesis were a Heck reaction of 1-bromo-2-iodobenzene with allyl alcohol, the introduction of a carboxy group after Br/Li-exchange, and the diastereoselective formation of the tricyclic oxazolidine system cis-2. Activation of cis-2 with TiCl₄ led to formation of a carbenium ion, which was attacked by allyltrimethylsilane exclusively from the Re-face leading to the (3S)-configured 2-benzazepinone 8 in 65% yield. The configuration of the new stereogenic center was determined by X-ray crystal structure analysis, which is the basis for the proposed mechanism of this transformation. Enantiomerically pure 3-substituted 2-benzazepines represent interesting drug candidates.     

Asymmetric Diels-Alder, Michael, and aldol reactions using a planar chiral 1,3-oxazol-2(3H)-one derived from (R)-(+)-4-hydroxy-[2.2]paracyclophane

(+)-(R)-[2.2]Paracyclophane[4,5-d]-1,3-oxazol-2(3H)-one exhibiting planar chirality has been used as a chiral auxiliary in asymmetric Diels-Alder, Michael, and aldol reactions of alpha,beta-unsaturated carboxy and enolate imides, respectively. The endo-exo- and face-diastereoselectivity is good and is controlled by the spatial relationship between the prochiral center and the C9-C10 ethylene bridge of the [2.2]paracyclophane moiety. The chiral auxiliary is easily removed and quantitatively recovered.     

2-Methyl-s-triazolo[1,5-b]isoquinolin-5(10H)-one

Acetamidrazone hydrochloride reacts with homophthalic anhydride to give 3-o-carboxybenzyl-5-methyl-1,2,4-triazole 1, which can be cyclised to 2-methyl-s-triazolo[1,5-b] isoquinolin-5(10H)-one 2. Reduction with lithium aluminium hydride gives 5,10-dihydro-2-methyl-s-triazolo [1,5-b] isoquinoline, while condensation with aromatic aldehydes gives 10-arylmethylene derivatives. Coupling with arenediazonium salts gives the 10-arylhydrazones of 5,10-dihydro-2-methyl-s-triazolo [1,5-b] isoquinoline-5,10-diones, while condensation with p-nitrosodimethylaniline gives the 10-imino derivative. Alkylation of 2 produces the corresponding 10,10-dialkyl derivatives.     

手性5-(R)-(1′R,2′S,5′R)-孟氧基丁内酯并[3,4-b]-2(S)-6(R)-1-N-环己基氮杂环丙烷的合成及晶体结构

环己胺与手性元5-(R)-(1′R,2′S,5′R)-孟氧基-3-溴-2(5H)-呋喃酮的不对称M ichael加成/分子内亲核取代反应,得到含有两个新手性中心的氮杂环丙烷/稠合丁内酯标题化合物。对其进行了谱学表征和X-射线单晶衍射测定。标题化合物分子式为C20H33NO3,M r=335.47,三斜晶系,P1空间群,晶胞参数:a=5.438(11)。A,b=8.117(2)。A,c=11.572(2)。A,α=96.84(3)°,β=94.48(3)°,γ=101.86(3),°V=493.5(2)。A3,Z=1,D c=1.129g/cm3,R=0.0867,wR=0.2344。     

Synthesis of (5S)-5-methylfuran-2(5H)-one and its dihydro derivative

(5S)-5-Methylfuran-2(5H)-one and (5S)-5-methyltetrahydrofuran-2-one were synthesized starting from L-lactic acid ethyl ester.     

Synthesis of imidazo[4,5-c]quinolin-4(5H)-one via radical cyclization

The tributyltin radical-induced cyclization of N-(2-bromophenyl)-Nbutyl-1H-1-methylimidazole-4-carbox-amide 3 gave 5-butyl-3-methyl-3H-imidazo[4,5-c]quinolin-4(5H)-one 5 via [1,2]-acyl rearrangement.     

Mesogenic properties of chiral compounds derived from 2( S )-[2( S )-ethylhexyloxy] propionic acid and its ( S, R )-diastereomer

Two acids, 2( S )-[2( S )-ethylhexyloxy] propionic acid and 2( S )-[2( R )-ethylhexyloxy] propionic acid, were used as the chiral building block for the preparation of four liquid crystals 5, 6, 7 and 8 . The diastereomers of the biphenyl ring system, 5 and 6 , possess the phase sequence I-N * -SmC * -Cr1-Cr2, while the diastereomers of the naphthalene ring system, 7 and 8 , exhibit the sequence I-SmA-SmC * -Cr. The temperature ranges of the SmC * phase for 5 and 6 are wider than those for 7 and 8 ; the phase transition temperatures of the SmC * phase for 7 and 8 are lower than those for 5 and 6 . In the case of the diastereomers of naphthalene ring system, the larger the size of the lateral substituent at the second chiral centre, i.e. ethyl or methyl group, the wider the temperature range of the SmC * phase.