O‐Benzyl‐N‐tert‐butoxy­carbonyl‐N‐methyl‐l‐tyrosine

The crystal structure of the title compound, alternatively called 3‐[4‐(benzyl­oxy)­phenyl]‐2‐(N‐tert‐butoxy­car­bonyl‐N‐methyl­amino)­propi­onic acid, C₂₂H₂₇NO₅, has been studied in order to ex­amine the role of N‐methyl­ation as a determinant of peptide conformation. The conformation of the tert‐butoxy­carbonyl group is trans–trans. The side chain has a folded conformation and the two phenyl rings are effectively perpendicular to one another. The carboxyl­ate hydroxyl group and the urethane carbonyl group form a strong intermolecular O—H?O hydrogen bond.     

Enantioselective Synthesis of Ethyl 4,5,7,8,9‐Penta‐O‐acetyl‐2,6‐anhydro‐ 3‐deoxy‐D‐erythro‐L‐gluca‐nononate: a 2‐Monodeoxygenated Derivative of `2‐Keto‐3‐deoxy‐D‐glycero‐D‐galacto‐nononic Acid'

A study aimed at developing an enantioselective synthesis of the title compound 23 , a 2‐monodeoxy analogue of the naturally occurring (+)‐2‐keto‐3‐deoxy‐D ‐glycero‐D ‐galacto‐2‐nononic acid (KDN), is reported. From D ‐mannose as starting material, the chiral 1,3‐diene 10 , activated by a silyloxy substituent at C(2), was prepared in six steps (Scheme 1). However, the intermediates were often contaminated with varying amounts of by‐products arising from overoxidation during cleavage with periodic acid. An alternative route starting from the inexpensive and readily available D ‐isoascorbic acid ( 12 ), though a little longer than the first, satisfactorily circumvented the purification problem and led to the desired dienes 17 in good yields (scheme 2). The [Co^II(S,S)‐(+)‐salen]‐catalyzed hetero‐Diels‐Alder reactions of the aforementioned dienes with ethyl glyoxylate proceeded smoothly at room temperature, giving the dihydropyrano adducts 18 in moderate yields (Scheme 3). Dihydroxylation of 18a followed by reduction of the keto function gave the desired 4,5‐trans dihydroxy moiety of the KDN framework (Scheme 4, see 21 ). The spectroscopic data of the penta‐O‐acetylated 2‐deoxy‐KDN ethyl ester 23 were consistent with those reported for the corresponding methyl ester derived from natural KDN.     

Neue molekulare Indium‐Zinn‐Sauerstoff‐ und Indium‐Zinn‐Natrium‐Sauerstoff‐Chlor‐Cluster

Abstract. The five‐membered heteroelement cluster THF · Cl₂In(O^tBu)₃Sn reacts with the sodium stannate [Na(O^tBu)₃Sn]₂ to produce either the new oxo‐centered alkoxo cluster ClInO[Sn(O^tBu)₂]₃ ( 1 ) (in low yield) or the heteroleptic alkoxo cluster Sn(O^tBu)₃InCl₃Na[Sn(O^tBu)₂]₂ ( 2 ). X‐ray diffraction analyses reveal that in compound 1 the polycyclic entity is made of three tin atoms which together with a central oxygen atom form a trigonal, almost planar triangle, perpendicular to which a further indium atom is connected through the oxygen atom. The metal atoms thus are arranged in a Sn₃In pyramid, the edges of which are all saturated by bridging tert‐butoxy groups. The indium atom has a further chloride ligand. Compound 2 has two trigonal bipyramids as building blocks which are fused together at a six coordinate indium atom. One of the bipyramids is of the type SnO₃In with tert‐butyl groups on the oxygen atoms, while the other has the composition InCl₃Na with chlorine atoms connecting the two metals. The sodium atom in 2 has further contacts to two plus one alkoxide groups which are part of a[Sn(O^tBu)₂]₂ dimer disposing of a Sn₂O₂ central cycle. The hetero element cluster in 2 thus combines three closed entities and its skeleton SnO₃InCl₃NaO₂Sn₂O₂ consists of three different metallic and two different non‐metallic elements.     

5‐Acetyl‐2‐amino‐6‐methyl‐4‐phenyl‐4H‐pyran‐3‐carbonitrile and 2‐amino‐5‐benzoyl‐6‐methyl‐4‐phenyl‐4H‐pyran‐3‐carbonitrile acetonitrile solvate

The syntheses, X‐ray structural investigations and calculations of the conformational preferences of the carbonyl substituent with respect to the pyran ring have been carried out for the two title compounds, viz. C₁₅H₁₄N₂O₂, (II), and C₂₀H₁₆N₂O₂·C₂H₃N, (III), respectively. In both mol­ecules, the heterocyclic ring adopts a flattened boat conformation. In (II), the carbonyl group and a double bond of the heterocyclic ring are syn, but in (III) they are anti. The carbonyl group forms a short contact with a methyl group H atom in (II). The dihedral angles between the pseudo‐axial phenyl substituent and the flat part of the pyran ring are 92.7 (1) and 93.2 (1)° in (II) and (III), respectively. In the crystal structure of (II), inter­molecular N—H⋯N and N—H⋯O hydrogen bonds link the mol­ecules into a sheet along the (103) plane, while in (III), they link the mol­ecules into ribbons along the a axis.     

An efficient synthesis of a class of novel N‐Alkyl‐N‐aryl‐4‐hydroxy‐1‐methyl‐2‐oxo‐1,2‐dihydro‐3‐quinolinecarbothioamides

The novel title compounds have been prepared in high yield by an optimized amide coupling followed by a Dieckmann cyclization. Additionally, this new route is amenable to preparative scale synthesis.     

Synthesis of 15‐Cyano‐12‐oxopentadecano‐15‐lactone and 15‐Cyano‐ 12‐oxopentadecano‐15‐lactam

15‐Cyano‐12‐oxopentadecano‐15‐lactone was synthesized in 59% total yield starting from 2‐nitrocyclododecanone by Michael addition to acrylaldehyde, followed by reaction with trimethylsilylcyanide, hydrolysis, ring‐expansion, and Nef reaction. A two‐step, one‐pot synthesis of intermediate 2‐hydroxy‐4‐(1‐nitro‐2‐oxycyclododecyl)butanenitrile from 3‐(1‐nitro‐2‐oxocyclododecyl)propanal was developed and the conditions for the Nef reaction were studied. 15‐Cyano‐12‐oxopentadecano‐15‐lactam was synthesized in 40% total yield starting from 2‐nitrocyclododecanone by Michael addition to acrylaldehyde, followed by Strecker reaction, ring‐expansion, and Nef reaction. The conditions for the Strecker and Nef reactions were studied. The structures of the target compounds, intermediates, and by‐product were characterized by IR, ¹H‐ and ¹³C‐NMR, and elemental analysis or MS.     

4‐Ethynyl‐4‐hydroxycyclohexan‐1‐one and 4‐ethynyl‐4‐hydroxy‐2,3,5,6‐tetramethylcyclohexa‐2,5‐dien‐1‐one

The title compounds, C₈H₁₀O₂, (I), and C₁₂H₁₄O₂, (II), occurred as by‐products in the controlled synthesis of a series of bis­(gem‐alkynols), prepared as part of an extensive study of synthon formation in simple gem‐alkynol derivatives. The two 4‐(gem‐alkynol)‐1‐ones crystallize in space group P2₁/c, (I) with Z′ = 1 and (II) with Z′ = 2. Both structures are dominated by O—H?O=C hydrogen bonds, which form simple chains in the cyclo­hexane derivative, (I), and centrosymmetric dimers, of both symmetry‐independent mol­ecules, in the cyclo­hexa‐2,5‐diene, (II). These strong synthons are further stabilized by C[triple‐bond]C—H?O=C, C_methylene—H?O(H) and C_methyl—H?O(H) interactions. The direct intermolecular interactions between donors and acceptors in the gem‐alkynol group, which characterize the bis­(gem‐alkynol) analogues of (I) and (II), are not present in the ketone derivatives studied here.     

Synthesis of Novel 3‐Acetyl‐2‐Aryl‐5‐(3‐Aryl‐1‐Phenyl‐Pyrazol‐4‐yl)‐2,3‐Dihydro‐1,3,4‐Oxadiazoles

A series of novel pyrazolyl‐substituted 1,3,4‐oxadiazole derivatives ( 4a‐4o ) were prepared by cyclization of the intermediate N′‐((3‐aryl‐l‐phenyl‐pyrazol‐4‐yl)methylene)arylhydrazide with acetic anhydride. The structures of the new compounds were confirmed by IR, ¹H NMR, MS and elemental analysis. Furthermore, preliminary bioassay of some of the title compounds indicated that they exhibited moderate inhibition against HIV‐1 PR.     

Synthesis of 1‐Amino‐5,6‐diaryl‐3‐cyano‐1H‐pyridin‐2‐ones and 6,7‐Diaryl‐4‐cyano‐3‐hydroxy‐1H‐[1,2]diazepines from Isoflavones

The one‐step cyclocondensation of substituted isoflavones (=3‐phenyl‐4H‐1‐benzopyran‐4‐ones) with cyanoacetohydrazide in the presence of KOH afforded a mixture of 1‐amino‐5,6‐diaryl‐3‐cyano‐1H‐2‐pyridin‐2‐ones and 6,7‐diaryl‐4‐cyano‐3‐hydroxy‐1H‐[1,2]diazepines.     

4‐Acetyl‐5‐methyl‐2‐phenyl‐1,2‐di­hydro‐3H‐pyrazol‐3‐one hydrate

The title compound, C₁₂H₁₂O₂N₂·H₂O, is described. Although the keto–enol form of the ligand in solution is known, the compound crystallized in the orthorhombic space group P2₁2₁2₁ with only the monohydrated 1,3‐diketo form. The intermolecular hydrogen bond between the imino N—H group of the ligand and O atom of the water mol­ecule recorded an H?O distance of 1.73 (3) Å.     

A New Solution—phase Parallel Synthesis of 2—Alkyamino—3—aryl—5—phenylmethylene—3,5—dihydro—4H—imidazol—4—ones

Thirteen new 2-alkylaminoimidazolones(4) wre rapidly synthesized by a new solution-phase parallel synthetic method,which includes aza-Wittig reaction of iminophosphorane(1) with aromatic isocyanate to give carbodi-imide(2) and subsequent reaction of 2 with various aliphatic primary amine in a parallel fashion.The products were confirmed by ^1H NMR,MS,IR and X-ray crystallographic analysis.The unusual selectivity of the cyclization was probably due to the deometry of the guanidine intermediate.     

Cyclization of 2‐benzoylamino‐N‐methyl‐thiobenzamides to 3‐methyl‐2‐phenylquinazolin‐4‐thiones

Acylation of 2‐amino‐N‐methyl‐thiobenzamide with substituted benzoyl chlorides has been used to synthesize the corresponding 2‐benzoylamino‐N‐methylthiobenzamides. Subsequent sodium methoxide‐catalyzed ring closure gives the corresponding 3‐methyl‐2‐phenylquinazoline‐4‐thiones. These compounds were characterized by means of their ¹H‐ and ¹²C‐NMR spectra. The kinetics of the cyclization reaction has been followed with UV‐VIS spectroscopy at 100 °C in methanolic solutions of sodium methoxide.     

rac‐5‐Diphenylacetyl‐2,2,4‐trimethyl‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepine and rac‐5‐formyl‐2,2,4‐trimethyl‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepine

rac‐5‐Diphenylacetyl‐2,2,4‐trimethyl‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepine, C₂₆H₂₇NOS, (I), and rac‐5‐formyl‐2,2,4‐trimethyl‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepine, C₁₃H₁₇NOS, (II), are both characterized by a planar configuration around the heterocyclic N atom. In contrast with the chair conformation of the parent benzothiazepine, which has no substituents at the heterocyclic N atom, the seven‐membered ring adopts a boat conformation in (I) and a conformation intermediate between boat and twist‐boat in (II). The molecules lack a symmetry plane, indicating distortions from the perfect boat or twist‐boat conformations. The supramolecular architectures are significantly different, depending in (I) on C—H...O interactions and intermolecular S...S contacts, and in (II) on a single aromatic π–π stacking interaction.     

Synthesis of Well‐Defined Rod‐Coil‐Rod Polyhexylisocyanate‐block‐polystyrene‐block‐polyhexylisocyanate via One‐Pot Anionic Polymerization

A rod‐coil‐rod block copolymer, polyhexylisocyanate‐block‐polystyrene‐block‐polyhexylisocyanate, of controlled molecular weight was synthesized quantitatively via living anionic polymerization using potassium naphthalenide in the presence of sodium tetraphenylborate. The use of K⁺ as the counterion for the polymerization of styrene, and Na⁺ (NaBPh₄) for the polymerization of isocyanate leads to the formation of a well‐controlled novel triblock copolymer.

     

Synthesis of some new 1‐acyl‐5‐aryl‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐4,5‐dihydro‐1H‐pyrazole

Some new compounds (E)‐3‐aryl‐1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐prop‐2‐en‐1‐ones 5a–e were prepared by 1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐ethanone and various aromatic aldehydes. Then one pot reaction was happened by compounds 5a–e with hydrazine hydrate in acetic acid or propionic acid, respectively, to give the title compounds 1acyl‐5‐aryl‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐4,5‐dihydro‐1H‐pyrazoles 6a–i . All structures were established by MS, IR, CHN, ¹H‐NMR and ¹³C‐NMR spectral data. J. Heterocyclic Chem., (2012).     

A simple synthesis of 5‐ethoxycarbonyl‐6‐phenyl‐1,3‐dioxin‐4‐ones and ethyl 3‐benzoyl‐4‐oxo‐2,6‐diphenylpyran‐5‐carboxylate

4‐Ethoxycarbonyl‐5‐phenyl‐2,3‐dihydrofuran‐2,3‐dione 1 reacts with aldehydes via the acylketene intermediate 2 giving the 1,3‐dioxin‐4‐ones 3a‐e and the 1,4‐bis(5‐ethoxycarbonyl‐4‐oxo‐6‐phenyl‐4H‐1,3‐dioxin‐2‐yl)benzene 4 , and a one step reaction between dibenzoylmethane and oxalylchloride gave 3,5‐dibenzoyl‐2,6‐diphenyl‐4‐pyrone 7 . The reaction of 1 with dibenzoylmethane, a dicarbonyl compound, provided ethyl 3‐benzoyl‐4‐oxo‐2,6‐diphenylpyran‐5‐carboxylate derivative 9 . Compound 9 was converted into the corresponding ethyl 3‐benzoyl‐4‐hydroxy‐2,6‐diphenylpyridine‐5‐carboxylate derivative 10 via its reaction with ammonium hydroxyde solution in 1 ‐butanol.     

3‐O‐Acetyl‐4‐deoxy‐4‐iodo‐β‐d‐fructo­furan­osyl 2,3,6‐tri‐O‐acetyl‐4‐chloro‐4‐deoxy‐α‐d‐gluco­pyran­oside

At 160 K, the gluco­pyran­osyl ring of the title compound, C₂₀H₂₈ClIO₁₃, has a near‐ideal ⁴C₁ conformation and the fructo­furan­osyl ring has a twist ⁴T₃ conformation. The two hydroxy groups are involved in intra‐ and intermolecular hydrogen bonds, with the latter interactions linking the mol­ecules into infinite one‐dimensional chains. The absolute configuration of the mol­ecule has been determined.     

Synthesis of pinacol esters of 1‐alkyl‐1H‐pyrazol‐5‐yl‐ and 1‐alkyl‐1H‐pyrazol‐4‐ylboronic acids

Starting from 1H‐pyrazol, a wide number of 1‐alkyl‐1H‐pyrazol‐4‐yl and 1‐alkyl‐1H‐pyrazol‐5‐ylboronic acids and their pinacol esters were synthesized and characterized. The key step in the described methodology is the regioselective lithiation of the pyrazole ring. The synthesized pinacolates are stable under prolonged storage and can be used as convenient reagents in organic synthesis.     

Synthesis and anti‐HIV activity of n‐(3‐amino‐3,4‐dihydro‐4‐oxopyrimidin‐2‐yl)‐4‐chloro‐2‐mercapto‐5‐methylbenzenesulfonamide derivatives

A series of N‐(3‐amino‐3,4‐dihydro‐4‐oxopyrimidin‐2‐yl)‐4‐chloro‐2‐mercapto‐5‐methylbenzenesulfonamide derivatives 10‐17 have been synthesized as potential anti‐HIV agents. The in vitro anti‐HIV‐1 activity of these compounds has been tested at the national Cancer Institute (Bethesda, MD), and the structure‐activity relationships are discussed. The selected N‐[3‐amino‐3,4‐dihydro‐6‐(tert‐butyl)‐4‐oxothieno[2,3‐e]pyrimidin‐2‐yl]‐4‐chloro‐2‐metcapto‐5‐methylbenzenesulfonamide ( 14 ) showed good anti‐HIV‐1 activity with 50% effective concentration (EC₅₀) value of 15 μM and weak cytotoxic effect (IC₅₀ = 106 μM).