The synthesis of β-heteroarylamino-α,β-dehydro-α-amino acid and β-heteroarylamino-α-amino acid derivatives

From heteroarylaminomethyleneoxazolones 4 , obtained from N-heteroarylformamidines 2 and 2-phenyl-5-oxo-4,5-dihydro-1,3-oxazole ( 3 ), the following β-heteroarylamino-α,β-dehydro-α-amino acid derivatives were prepared: methyl 8 and ethyl esters 9 , amides 10 and 11 , hydrazides 12 , and azides 15 . By catalytic hydrogenation the compounds 4 were converted into β-heteroarylamino substituted amides 18 and β-heteroarylamino-α-amino acids 20 .     

Reaction of α,β-unsaturated carbodiimides with enamines leading to fused pyridine derivatives

The treatment of (5,5-dimethyl-3-oxo-1-cyclohexenyl)iminotriphenylphosphorane ( 2 ) with phenyl isocyanate ( 3a ) gave N-(5,5-dimethyl-3-oxo-1-cyclohexenyl)-N'-phenylcarbodiimide ( 4a ) in situ. The reaction of 4a with enamines proceeded smoothly to afford the pyridine ring formation with the elimination of amine. This means that 4a is regarded as a new class of 2-aza-1,3-butadiene. The scopes and limitation of this reaction are also discussed.     

The synthesis of β-heteroarylamino-α,β-dehydro-α-amino acid derivatives via thiazolones

2-Alkoxy-4-heteroarylaminomethylene-5(4H)-thiazolones 4 were converted with various nucleophiles into β-heteroarylamino-α,β-dehydro-α-amino acid derivatives 11, 14, 15, 16, 17, 18 , and 19 . Reduction of 4 with sodium borohydride in ethanol saturated with gaseous ammonia afforded the corresponding β-heteroaryl-amino substituted alanyl amides 20 . Thiazoledione derivative 7a was transformed with sodium methoxide in methanol into 1-(4,6-dimethylpyrimidinyl-2)-4-mercaptocarbonylimidazol-2(3H)-one ( 8a ).     

Reaction of α,β-poly(N-hydroxyethyl)-DL-aspartamide with derivatives of carboxylic acids

Benzoic acid, acetylsalicylic acid, and 4-acetamidobenzoic acid have been covalently linked by ester bonds to α,β-poly(N-hydroxyethyl)-DL -aspartamide (PHEA), a water soluble and nontoxic polymer, in order to study PHEA as a drug carrier.     

γ-Lactones from malonic acid derivatives

The acid catalyzed cyclization of isopropylidene malonate derivatives of ketones to form α-earboxy-γ-lactones has been shown to occur with boron trifluoride etherate or p-toluenesulfonic acid, as well as with concentrated sulfuric or polyphosphoric acids. A similar cyclization of a diethyl ylidenemalonate to a lactone ester, in relatively poor yield, has also been accomplished. Acid catalyzed cyclization of the ylidenemalononitrile derived from pinacolone to form an α-carbamoyl-γ-lactone has been shown to occur with rearrangement. However, that derived from 2,2-dimethyleyclohexanone cyclized to the secondary carbon of the ring without rearrangement. The isopropylidene malonate derivatives of several ring-substituted and bridged ketones have been converted to α-earboxy-γ-laetones without rearrangement.     

Preparation and antibacterial activity of aromatic derivatives of β-aminopropionic and γ-aminobutyric acid

Ten aromatic derivatives of β-aminopropionic acid and γ-aminobutyric acid were prepared.Their compositions and structures were identified by elemental analysis,IR,and 1H NMR.They have been examined for their antibacterial action against Staphylococcua aurens and Escherichia coli.These compounds showed higher activity than the aromatic derivatives of ct-amino acid which were reported previously.The general conclusion to be drawn is that the distance between amino and carboxylic group in these molecules could affect their antibacterial activity.Furthermore,those compounds with p-methyl substituent in phenyl ring exhibit higher activity than the others,and all the compounds exhibit higher activity against Escherichia coli and against Staphylococcua aureus.     

Room-temperature polycondensation of β-amino acid derivatives. V. Synthesis of hydrophilic polyamide by the polycondensation of β-amino acid derivatives

N-(Hydroxyalkyl) β-alanine ester which was obtained from amino alcohol and acrylate yielded polyamide at room temperature in the presence of a basic catalyst. Alkali and alkali earth metal alkoxides had a strong catalytic effect on the room-temperature polycondensation of N-(hydroxyethyl)-β-alanine esters. The catalytic activity of metal alkoxides decreased in the order: Li > Na > K > Cs and Ca > Zn > Mg. Aluminum and titanium alkoxide had a weak catalytic effect, while boron (III), tin (IV), antimony (V), and tellurium (VI) alkoxides did not show any catalytic activity for the polycondensation. It was also found that solvent had an effect on the course of the polycondensation of N-(hydroxyethyl)-β-alanine esters, and the highest molecular weight polymer was formed only in methanol solution. The solid-phase polycondensation of the low molecular weight prepolymer resulted in a high molecular weight polymer with an inherent viscosity of 1.0 in the presence of a catalytic amount of phosphoric acid. The polymer obtained is hydrophilic and its moisture absorption is more than twice that of nylon 6.     

Reaction of singlet oxygen with α,β-unsaturated aldimines

The reaction of singlet oxygen with N-1-(2-alkenylidene)-t- butylamines ( and ) gives the unsaturated hemiperacetal derivatives ( and 4) of the hydroperoxy aldimines ( and ). Several α, β-unsaturated aldimines which are held in the s-trans conformation failed to react with singlet oxygen.     

The chemistry of coumarin derivatives,part 2. Reaction of 4-hydroxycoumarin with α,β-unsaturated aldehydes

4-Hydroxycoumarin (= 4-hydroxy-2H-1-benzopyran-2-one) reacts with enals to give 1,2- or 1,4-addition products, depending on the nature and relative location of the substituents on the olefinic double bond (Scheme 2). The resulting adducts further react intra- or intermolecularly, affording dimeric coumarins or pyranocoumarins in the case of 1,2-addition and acetalic pyranocoumarins in the case of 1,4-addition. With enals bearing alkyl groups at C(β), 2H-pyrano[3,2-c]coumarins are the only products formed, and the reaction represents an easy and straightforward entry into this class of recently described biologically active natural products.     

Reaction of ninhydrin with β-dicarbonyl compounds

The reactions of ninhydrin ( 1 ) with β-ketoesters and β-diketones were studied. Two kinds of products were observed, which were either simple adducts of the dicarbonyl compounds to the center carbonyl group of ninhydrin, or tricyclic indeno[1,2-b]furans. Treatment of methyl 3-aminocrotonate ( 2 ) with ninhydrin led in analogous fashion to an indeno[1,2-b]pyrrole ( 3 ) which was reduced to a complex tetracyclic dihydropyridine 12 . A mechanism for the production of 12 is presented. Structures for the novel heterocycles are supported by high resolution nmr studies and X-ray crystallography.     

Four oxoindole‐linked α‐alkoxy‐β‐amino acid derivatives

Four structures of oxoindolyl α‐hydroxy‐β‐amino acid derivatives, namely, methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐methoxy‐2‐phenylacetate, C₂₄H₂₈N₂O₆, (I), methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐ethoxy‐2‐phenylacetate, C₂₅H₃₀N₂O₆, (II), methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐[(4‐methoxybenzyl)oxy]‐2‐phenylacetate, C₃₁H₃₄N₂O₇, (III), and methyl 2‐[(anthracen‐9‐yl)methoxy]‐2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐phenylacetate, C₃₈H₃₆N₂O₆, (IV), have been determined. The diastereoselectivity of the chemical reaction involving α‐diazoesters and isatin imines in the presence of benzyl alcohol is confirmed through the relative configuration of the two stereogenic centres. In esters (I) and (III), the amide group adopts an anti conformation, whereas the conformation is syn in esters (II) and (IV). Nevertheless, the amide group forms intramolecular N—H...O hydrogen bonds with the ester and ether O atoms in all four structures. The ether‐linked substituents are in the extended conformation in all four structures. Ester (II) is dominated by intermolecular N—H...O hydrogen‐bond interactions. In contrast, the remaining three structures are sustained by C—H...O hydrogen‐bond interactions.     

Transformations of isomeric naphthopyranones. The synthesis of substituted β-naphthyl-α,β-dehydro-α-amino acid derivatives

The opening of the pyranone ring in 2H-naphtho[1,2-b]pyran-2-one derivative (1) and 3H-naphtho[2,1-b]-pyran-3-one derivatives 8 and 20 with nucleophiles afforded 3-(naphthyl-1)- and 3-(naphthyl-2)propenoates (substituted β-naphthyl-α,β-dehydro-α-amino acid derivatives) 7, 13, 14, 15, 24 , and 35 .     

The Reaction of Singlet Oxygen with α- and β-Pinenes

The reaction of photogenerated singlet oxygen with α- and β-pinenes has been carefully re-examined. α-Pinene almost exclusively (99.3% yield) furnishes trans-3-hydroperoxy-pin2(10)-ene. However, detectable amounts of the three other possible products are also found, viz., cis-3-hydroperoxypin-2 (10)-ene (?0.8%), and cis- and trans-2-hydroperoxypin-3 (4)-ene (?0.04%). β-Pinene gives 99.9% of 10-hydroperoxypin-2 (3)-ene and a trace (?0.01%) of norpinan-2-one. Rates of reaction and product composition are treated by modal analysis and reflect the operation of steric and stereoelectronic factors in a reactant-like transition state.     

Applications of 1,4-addition of grignard reagents to α,β-unsaturated acid derivatives. III—configuration studies of α,β-diaryl-α,β-dialkylpropionitriles

The configuration of twenty-four different α,β-diaryl-α,β-dialkylpropionitriles has been determined using nuclear magnetic resonance spectra. The erythro form showed greater deshielding of the methine hydrogen and alkyl groups in its spectra than the corresponding threo isomer. The former, however, showed less deshielding of the aryl groups than the threo isomer. Infrared spectra were not suitable for assignments of configuration.     

An effective synthesis of α-glycosides of -acetylneuraminic acid derivatives by use of 2-deoxy-2β-halo-3β-hydroxy-4,7,8,9-tetra- -acetyl- -acetylneuraminic acid methyl ester

Condensation of a new glycosyl donor, methyl 5-acetamido-4, 7,8,9-tetra- -acetyl-2,3-dibromo-2,3,5-trideoxy-β- -2-nonulopyranosonate with various acceptors such as methyl 2,3,4-tri- -benzyl-α- -glucopyranoside, cholesterol, methyl 2,4,6-tri- -bonzyl-α- -galactopyranoside, and nethyl 5-acetamido-4,7,9-tri- -acetyl-2,6-anhydro-3,5-dideoxy- -non-2-enopyranosonate gave only the corresponding β-glycosides. The 3α-bromo group of the glycoaides obtained above was reduced with tributylstannane to the corresponding glycosids, which were deprotected to give the free glycoaides in high yields.     

Reaction of α,β-unsaturated acid chlorides with β-diketones. Synthesis of 4,6,7,8-tetrahydro-2H-1-benzopyran-2,5(3H)-diones

Reaction of an α,β-unsaturated acid chloride with the anion of 5,5-dimethyl-1,3-cyclohexane-dione ( 2 ) gives either the enol ester ( 4 ) or a cyclized product ( 5 ), depending upon the reaction conditions. When the acid chloride is in excess, the ester is obtained. When the anion is in excess and the acid chloride is acryloyl or crotonyl, the cyclized product is obtained. A similar cyclized product ( 9 ) was formed from acryloyl chloride and an excess of the anion of 4-hydroxy-6-methyl-2-pyrone ( 8 ).     

Reaction products of 2-aminobenzenethiol with some β-diketones

2-Aminobenzenethiol undergoes condensation reactions with several β-diketones (CH₃, CF₃ and C₆H₅ substituents) to form benzothiazolines. Conversion to benzothiazines and benzothiazoles occurs in some instances, as documented by the isolation and spectroscopic characterization of the products.     

[3+3] Cyclization reactions of β-nitroenamines and β-enaminonitriles with α,β-unsaturated carboxylic acid chlorides

New indolizidines, quinolizidines, and octahydro-pyrido[1,2-a]azepines of lactam type were synthesized from 2-nitromethylene-pyrrolidine, -piperidine, and -hexahydroazepine, respectively, by [3+3] cyclizations with α,β-unsaturated carboxylic acid chlorides. In the case of quinolizidines, a double bond migration was observed, and explained in terms of amidity percentage. Cyanomethylene-pyrrolidine gave indolizidines of lactam type, while transformations of 1-cyanomethylene-tetrahydoisoquinoline resulted in lactams as well as ketones, when simple open-chain acid chlorides or cinnamoyl chloride were used, respectively.     

A Mild Isomerization Reaction for β,γ‐Unsaturated Ketone to α,β‐Unsaturated Ketone

A series of β,γ‐unsaturated ketones were isomerized to their corresponding α,β‐unsaturated ketones by the introduction of DABCO in iPrOH at room temperature. The endo‐cyclic double bond (β,γ‐position) on ketone was rearranged to exo‐cyclic double bond (α,β‐position) under the reaction conditions.