Reaction of 3-Carene with Some Nitrating Agents

From the reaction products obtained by treating 3-carene with dinitrogen tetroxide a crystalline compound N-[(1R,6R)-3-methyl-6-(1-methyl-1-nitroxyethyl)cyclohex-3-enyl]-N'-{1S,6S)-4- methyl-6(1- methyl-1-nitroxyethyl)cyclo-hex-3-enyl]-E-diazene-N,N'-dioxide was isolated. Mainly nitrate of -terpineol formed in reaction of 3-carene with 70% nitric acid.     

Structure and conformational features of tetrahydrothienothiepinoisoxazole as a novel heterocyclic system

The crystal and molecular structure of a novel heterocyclic system, 8-methyl-3,3a,4,5-tetrahydrothieno[3,2:6,7]thiepino[4,5-c]isoxazole, has been determined by X-ray analysis. The seven-membered ring has the boat conformation (B), while the isoxazoline cycle has the flat chair conformation (₃E). There are strong steric strains between the vicinal protons at the C(3a), C(3), and C(4) atoms.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1795–1797, October, 1994.     

Concise, enantiospecific synthesis of (3S,4R)-3-amino-4-ethylpiperidine as partner to a non-fluoroquinolone nucleus

An enantiospecific, eight-step synthesis of (3S,4R)-3-amino-4-ethylpiperidine 3 starting from readily available (S)-(−)-α-methyl-4-pyridinemethanol 6 has been achieved utilizing an Overman rearrangement of a chiral allylic trichloroacetimidate 13 as the key step. A diastereoselective hydrogenation of the resulting chiral allylic amine 15 afforded predominantly the desired trans-substituted piperidine. The conformation of the piperidine along with the directing nature of the amino function are implicated in the selectivity observed.     

Chiral β-hydroxycarbonyl compounds based on (−)-menthone: structure and behavior in liquid crystalline systems

It has been established by X-ray structural analysis that 2-(1-biphenyl-4-yl-1-hydroxy)methyl-p-menthan-3-one, one of the products of the reaction of (–)-menthone triisopropyloxytitanium enolate with 4-phenylbenzaldehyde, has a 1R,2S,4S,1S configuration. In crystals, this -hydroxyketone adopts a chair conformation with equatorial methyl and isopropyl groups and an axial 2-(1-biphenyl-4-yl-1-hydroxy)methyl substituent. Unlike the stereoisomeric compound with the 1R,2S,4S,1S configuration, the exocyclic fragment of which has an intramolecular >C=O...H-O- hydrogen bond in crystals and solutions, in the crystals of the 1R,2S,4S,1S ketol under study, molecules are linked by a network of cooperative -O-H...O-H...O-H... hydrogen bonds. Based on the results of molecular mechanics calculations and experimental data of¹H NMR and IR spectroscopy, conformations of molecules of this compound, which are in equilibrium in solution, have been characterized. Based on data on spatial structures of stereoisomeric -hydroxyketones and the character of H-bonds formed by these compounds, the characteristic features of the effect of these chiral alloying additives on the supramolecular structure and macroscopic properties of liquid crystalline systems have been interpreted.The results of a study of stereoselectivity of the reactions of different (–)-menthone enolates with aromatic aldehydes will be published later.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1247–1255, July, 1995.The work was supported by the Foundation for Basic Research of the State Science and Engineering Committee of Ukraine (Project No. 93-3.2/75).     

Synthesis of Enantiomerically Pure 2-Isoxacephems

Summary. (R,6R,7R)-7-(1-Acetoxyethyl)-3-methyl-2-isoxacephem-4-carboxylic acid and its enantiomer have been prepared. The ring systems were formed from the corresponding enantiomerically pure N-unsubstituted -lactams. The reduction of methyl [(R,2S,3R)-3-(1-acetoxyethyl)-1-(4-methoxyphenyl)-4-oxoazetidine-2-carboxylate] has been solved via a hemi-acetal. The structure and the configuration of a new stereogenic center in this intermediate was predicted by using 2D NMR technique and unambiguously proven by x-ray.     

Synthesis of Enantiomerically Pure 2-Isoxacephems

(R,6R,7R)-7-(1-Acetoxyethyl)-3-methyl-2-isoxacephem-4-carboxylic acid and its enantiomer have been prepared. The ring systems were formed from the corresponding enantiomerically pure N-unsubstituted -lactams. The reduction of methyl [(R,2S,3R)-3-(1-acetoxyethyl)-1-(4-methoxyphenyl)-4-oxoazetidine-2-carboxylate] has been solved via a hemi-acetal. The structure and the configuration of a new stereogenic center in this intermediate was predicted by using 2D NMR technique and unambiguously proven by x-ray.     

Asymmetric Synthesis of Highly Enantiomerically Enriched (S)(-)-β-Bisabolene

(S)-β-Bisabolene, (S)-1, was synthetized by a synthetic route in which (S)-4-methyl-3-cyclohexene carboxylic acid, (S)-10, which was the key intermediate, was prepared via a highly diastereoselective TiCl₄-catalyzed Diels-Alder reaction between isoprene and the acrylate of commercial (R)-pantolactone, followed by hydrolysis. Compound (S)-10 was then converted into ketone (S)-13 using two different procedures. The best one of these, as regards the degree of stereospecificity, involved the reaction of (S)-10 with 2 equiv of 4-methyl-3-penten-1-yllithium, 14, in the presence of CeCl₃, and gave (S)-13 having ca. 84% ee. The Zr-promoted methylenation of this ketone afforded highly enantiomerically enriched (S)-1.     

Zur Stereochemie der aromatischen Claisen-Umlagerung. Thermische Umlagerung von erythroiden und threoiden ortho-Dienonen

On the Stereochemistry of the Aromatic Claisen Rearrangement. Thermal Rearrangement of erythroid and threoid ortho-Dienones. Erythro- and threo-1-methyl-1-(1′-methyl-2′-propynyl)-2-oxo-1,2-dihydronaph-thalene (erythro- and threo- 6 ) as well as erythro- and threo-2,6-dimethyl-6-(1′-methyl-2′-propynyl)-cyclohexa-2,4-dien-1-one (erythro- and threo- 8 ) were obtained together with the corresponding aromatic ethers 5 and 7 by alkylation of 1-methyl-2-naphthol and 2,6-dimethyl-phenol, respectively in alcoholic potassium hydroxide solution with 1-methyl-2-propynyl p-toluenesulfonate (Scheme 2). The diastereoisomeric dienones 6 and 8 were easily separated by column chromatography on silica gel and its relative configuration at C(1) or C(6) and C(1′) deduced from the chemical shifts in their ¹H-NMR.-spectra (Table 1). Hydrogenation of 6 and 8 using Lindlar catalyst yielded the corresponding erythro- and threo-configurated (1′-methyl-2′-propenyl)-dienones 10 and 13 , respectively (Scheme 3) the thermal rearrangement of which were studied. The following results were obtained: threo- 10 rearranged in benzene at 85–105° preferentially via a chair-like (C) transition state to yield 99,5% (E)- and 0,5% (Z)-(2′-butenyl) 1-methyl-2-naphthyl ether ((E)- and (Z)- 14 ; ΔΔG (C/B) = ?4,0 kcal/mol). On the other hand, erythro- 10 when heated at 105-125° in benzene gave 84,7% (E)- and 15,3% (Z)- 14 , i.e. in this case a boat-like (B) transition state is favoured (G (C/B) = + 1,3 kcal/mol) (Scheme 5 and Table 2). The thermal rearrangement of dienones 13 led to the corresponding ethers 12 as well as p-allyl-phenols 11 . Thus, heating of threo- 13 at 20–42° in cyclohexane resulted in the formation of 2,5% of ether 12 , consisting of 98% of the (E)- and 2% of the (Z)-isomer, and 97,5% of (E)- 11 which contained, at a maximum, 0,5% of the (Z)-isomer, (Scheme 6 and Table 3). This means that both rearrangements occurred with a strong preference of the C transition state (G ( C/B , phenol) = ?3,3 kcal/mol). On the contrary, erythro- 13 when heated at 42–68° in cyclohexane yielded a 3:2 mixture of ether 12 and phenol 11 (Scheme 6). The ethereal part consisted of 88,0% of the (E)- and 12,0% of the (Z)-isomer which again shows that the B geometry predominated in the erythro transition state leading to the ether (G ( C / B )= + 1,3 kcal/mol). In the phenolic part 36–40% of the (E)-isomer and 64–60% of (Z)-isomer were found which means that in the para-Claisen rearrangement of erythro- 13 the C arrangement is only slightly favoured (ΔΔG ( C / B )= ?0,36 kcal/mol).     

Polar steroidal compounds from the Far-Eastern starfish Lethasterias nanimensis chelifera

In addition to the salts described previously (with a sulfated steroid as the anion and the alkaloid salsolinol as the cation), nine other steroidal compounds including three new compounds were isolated from the Far-Eastern starfish Lethasterias nanimensis chelifera collected near the coast of the Onekotan island (Kuril isles). A nonsteroidal compound found in this starfish is (1S,3S)-1-methyl-1,2,3,4-tetrahydro--carboline-3-carboxylic acid. The structures of the isolated compounds were determined by NMR spectroscopy and mass spectrometry.     

A study of methylation of inorganic tin by iodomethane in an aquatic environment with 13C carbon isotope tracer technique

The methylation of tin(II) [Sn(II)] by iodomethane (CH₃I) under environmental conditions has been further demonstrated by a ¹³C carbon isotope tracer method. Methylation products are mainly monomethyltin, and very small amounts of dimethyltin. The reaction of Sn(II) and CH₃I was investigated at pH 2, 4, 6, 8, 10 and salinity (S) 8, 15, 22, 28, 35%; it has been found the reaction was affected by pH and salinity, the tin methylation activity being highest at about pH 6 and S = 28% . The methylation reaction is first-order for both CH₃I and Sn(II), and the rate equation has been obtained as follows: .     

Reactions of (1R,2S)-1,2-di(2-furyl)-1,2-di(3-guaiazulenyl)ethane and (1R,2S)-1,2-di(3-guaiazulenyl)-1,2-di(2-thienyl)ethane with tetracyanoethylene (TCNE) in benzene: comparative studies on the products and their spectroscopic properties

Reactions of the title meso forms, (1R,2S)-1,2-di(2-furyl)-1,2-di(3-guaiazulenyl)ethane (1) and (1R,2S)-1,2-di(3-guaiazulenyl)-1,2-di(2-thienyl)ethane (2), with a two molar amount of TCNE in benzene at 25 °C for 5 h (for 1) and 48 h (for 2) under oxygen give new compounds, 2,2,3,3-tetracyano-4-(2-furyl)-8-isopropyl-6-methyl-1,4-dihydrocyclohepta[c,d]azulene (3) and 2,2,3,3-tetracyano-8-isopropyl-6-methyl-4-(2-thienyl)-1,4-dihydrocyclohepta[c,d]azulene (4), respectively, in 74 and 21% isolated yields. Comparative studies on the above reactions as well as the spectroscopic properties of the unique products 3 and 4, possessing interesting molecular structures, are reported and, further, a plausible reaction pathway for the formation of these products is described.     

Synthesis of (5R)- and (5S)-5-Methyl-5, 6-dihydrouridine Derivatives

The hydrogenation of 2′, 3′-O-isopropylidene-5-methyluridine (1) in water over 5% Rh/Al₂O₃ gave (5 R)- and (5 S)-5-methyl-5, 6-dihydrouridine (2) , separated as 5′-O-(p-tolylsulfonyl)- (3) and 5′-O-benzoyl- (5) derivatives by preparative TLC. on silica gel and ether/hexane developments. The diastereoisomeric differentiation at the C(5) chiral centre depends upon the reaction media and the nature of the protecting group attached to the ribosyl moiety. The synthesis of iodo derivatives (5 R)- and (5 S)- 4 is also described. The diastereoisomers 4 were converted into (5 R)- and (5 S)-2′, 3′,-O-isopropylidene-5-methyl-2, 5′-anhydro-5, 6-dihydrouridine (7) .     

Preparation and reactions of optically active cyanohydrins using the (R)-hydroxynitrile lyase from Prunus amygdalus

Cyanuration of 2-naphthaldehyde (1) and 5-methyl-2-furaldehyde (2) yielded the racemic 2-hydroxy-2-(β-naphthyl)ethanenitrile (R,S)-3 and 2-hydroxy-2-(5-methyl-2-furyl)ethanenitrile (R,S)-5, respectively. The same reaction can be completed by using acetone cyanohydrin (4) as a transcyanating agent. The optically active (R)-3 and (S)-5 could be respectively obtained by hydrocyanation of 1 and 2 using (R)-hydroxynitrile lyase (R)-PaHNL [EC 4.1.2.10] from almonds (Prunus amygdalus) as a chiral catalyst. Cyanohydrins 3 and 5 in their racemic and optically active forms undergo a number of transformations which involve either the hydroxyl group or the cyanide function. Moreover, derivatization of 3 and 5 with (S)-Naproxen®chloride (S)-14 gave the respective diastereoisomers. The optical activity of (R)-3 and (S)-5 as well as their derivatives were recorded. The postulated structures for the new products were supported with compatible elementary and spectroscopic (IR, ¹H NMR, ¹³C NMR, MS, and single crystal X-Ray crystallography) analyses. The antimicrobial activity of some selected racemic new products and their respective optically active analogues were also undertaken.     

Reactions of (1S,3S)-3-acetoxymethyl-1-(2-acetoxyvinyl)-2,2-dimethylcyclopropane with haloforms under conditions of phase-transfer catalysis

Heating of (1S,3S)-3-acetoxymethyl-1-(2-acetoxyvinyl)-2,2-dimethylcyclopropane with bromoform under phase-transfer catalysis affords dibromocyclopropane viaaddition of dibromocarbene to the double bond. In an analogous reaction with chloroform, the trichloromethyl anion adds to the double bond in the -position with respect to the acetoxy group.     

A mechanistic study on the intramolecular ionic Diels-Alder reaction of 2-methyl-3,9,11-tridecatriene-2-ol and 2,11-dimethyl-1,3,9,11-dodecatetraene

Intramolecular ionic Diels-Alder reaction of 2-methyl-3,9,11-tridecatriene-2-ol (1) was studied under acidic conditions. Treatment of 2-methyl-3,9,11-tridecatriene-2-ol (1) with trifluoromethanesulfonic acid yielded 7-methyl-8-isopropenyl-1,2,3,4,4aR^∗,7R^∗,8R^∗,8aS^∗-octahydronaphthalene (4) and (1Z)-1-((E)-but-2-enylidene)-2-(2-methylpropenyl)cyclohexane (5) through regioselective intramolecular ionic Diels-Alder reaction. The reaction appeared to proceed partly through a stepwise mechanism involving a carbocation intermediate. However, a concerted pathway rather than a stepwise one is suggested to be involved in the acid-catalyzed intramolecular Diels-Alder reaction of 2,11-dimethyl-1,3,9,11-dodecatetraene (13).     

Synthesis of ‘thianthrene dimer’ by the coupling reaction of stannylthianthrenes in the presence of copper catalysts

The coupling reaction of 1-tributylstannylthianthrene (5) and 2-tributylstannylthianthrene (7) in the presence of copper catalysts at rt afforded the thianthrene dimer 1,1′-bithianthrene (3), 2,2′-bithianthrene (8), and 1,2′-dithianthrene (9) in high yields. Also we obtained thianthrene oxide dimer (R,R) (S,S)-1-(10-S-monoxythianthrene-1-yl)thianthrene-10-S-monoxide (12) and (R,S) (S,R)-1-(10-S-monoxythianthrene-1-yl)thianthrene-10-S-monoxide (13) from 1-tributylstannyl-10-S-monoxythianthrene (10) under the same reaction condition. The final structural conformation of 3, 8, 9, and 12 was performed by X-ray crystallographic analysis. Further, the solvent effects in the coupling reactions were also examined.     

Complexation and hydrogenation of methionine-containing N-acetyle-dehydrodipeptides

The hydrogenation of the Fe^II complex ofN-Ac-Phe-(S)- or -(R)-Met over a Pd/C catalyst affords mainlyN-Ac-(R)-Phe-(S)-Met orN-Ac-(S)-Phe-(R)-Met, correspondingly. In the reaction of mixed dipeptide complexes with Ca^II and Fe^II the predominance of one of the diastereomers increases from 26 % (for complexes with Fe ions) to 38 %.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 545–546, March, 1994.The work was financially supported by the Russian Foundation for Basic Research (project No. 93-03-4646).     

Synthesis of (4R,8R)- and (4S,8R)-4,8-dimethyldecanal: the common aggregation pheromone of flour beetles

The synthesis of (4R,8R)- and (4S,8R)-4,8-dimethyldecanal 1 and 1a has been achieved connecting the chiral building block (R)-2-methyl-1-bromobutane 4 with (R)- and (S)-citronellol derivatives. The key intermediate 4 was obtained optically pure in five steps from methyl (S)-3-hydroxy-2-methylpropionate 2.     

Conformational analysis 29: Preparation and1H and13C NMR,FTIR, MS,and crystallographic conformational and configurational study of 3-Oxo-1,3-oxathiane and its monomethyl derivatives

3-Oxo-1,3-oxathiane (1) and its monomethyl derivatives were prepared by oxidation of the corresponding 1,3-oxathianes. The structural analysis was carried out by¹H and¹³C NMR, FTIR, and mass spectrometry. At 298 K compound1 was a 1 1 (at 173 K a 3 1) mixture of the SO(ax) and SO(eq) chair forms. The major oxidation products of methyl 1,3-oxathianes attained exclusively the SO(ax), Me(eq) chair forms except that of the 5-methyl derivative, which consisted of 7% of the SO(eq), Me(ax) chair conformation in CDCl₃ solution. The minor products of oxidation existed in anancomeric SO(eq), Me(eq) chair conformations. The oxidation of 2-methyl- 1,3-oxathiane, however, led to 3,3-dioxo derivative (6) in addition to thetrans [SO(eq)] monoxide. The crystal structures of6 andtrans-3-oxo-5-methyl-1,3-oxathiane were solved by X-ray diffractometry.     

Synthesis of modified ether phospholipids

A number of modified ether phospholipids with additional substituents in the 2 position of the C(1)-alkyl chain, 1-O-[2-(R,S)-hydroxyhexadecyl]-2-O-methyl-rac-glycero-3-phosphocholine, 1-O-[2-(R,S)-acetoxyhexadecyl]-2-O-methyl-rac-glycero-3-phosphocholine, 1-O-[2-(R,S)-hydroxyhexadecyl]-2-chloro-2-deoxy-rac-glycero-3-phosphocholine, and 1-O-[2-(R,S)-acetoxyhexadecyl]-2-chloro-2-deoxy-rac-glycero-3-phosphocholine, have been synthesized.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 974–978, May, 1995.We thank Dr. V. S. Pashkov for spectroscopic measurements and Dr. M. V. Anikin for spectroscopic measurements and scientific discussions.This work was partially supported by the Russian Foundation for Basic Research (Project No. 94-03-08166).