Synthesis and transformation of novel cyclic β-amino acid derivatives from (+)-3-carene

The regio- and stereoselective addition of chlorosulfonyl isocyanate to (+)-3-carene 1 resulted in β-lactam 2, which was converted to N-Boc-β-amino acid 4, β-amino ester 7, and carboxamide derivatives 18 and 20 via N-Boc activation and mild ring opening. The corresponding β-amino ester 7 was transformed to 2-thioxopyrimidin-4-one 11 and 2,4-pyrimidinedione 13. LAH reduction of 5 and 7 resulted in amino alcohols 6 and 8. The reaction of 8 with phenyl isothiocyanate, followed by cyclisation, furnished 1,3-oxazine 15.     

Photolysis of methyl ester of 1β,2β-epoxy-3-keto derivative of gibberellin A1

Conclusion A study was made of the photolytic opening of the epoxide ring in the methyl ester of the 1,2-epoxy-3-keto derivative of gibberellin A₁, which led to the formation of the methyl ester of 1,3-dihydroxyepial-logibberic acid and the methyl ester of the 1-hydroxy-3-keto derivative of gibberellin A₁.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 2, pp. 459–461, February, 1972.     

Cationic ring‐opening polymerization of six‐membered cyclic carbonates with ester groups

This work deals with the cationic ring‐opening polymerization of the ester‐substituted cyclic carbonates 5‐methyl‐5‐benzoyloxymethyl‐1,3‐dioxan‐2‐one ( CC1 ) and 4‐benzoyloxymethyl‐1,3‐dioxan‐2‐one ( CC4 ). The polymerization was carried out with trifluoromethanesulfonic acid, methyl trifluoromethanesulfonate, boron trifluoride etherate, or methyl iodide as the initiator. The reactivity of CC1 and CC4 was higher than that of 5,5‐dimethyl‐1,3‐dioxan‐2‐one, which had no ester moiety. These results suggest that this ring‐opening polymerization was accelerated by the intramolecular ester group. CC1 showed a higher polymerizability than CC4 , affording a polymer with a higher molecular weight. Additionally, using methyl iodide as the initiator was effective for increasing the molecular weight of the obtained polycarbonate and decreasing decarboxylation. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1305–1317, 2001     

Synthesis and aikylation of CIS-α-hydroxyisopropylindanone-2-carboxylic acid lactone

The Meldrum's acid adduct of isobutyrophenone was cyclized directly and in high yield to the title compound, which could then be alkylated at the 2-position with methyl iodide or ethyl 6-bromohexanoate. In the latter case, acid hydrolysis of the resultant ester gave the analogous acid, but alkaline hydrolysis resulted in ring opening of the indanone portion of the molecule.     

N- and O-carbamoyl and thiocarbamoyl derivatives of B-lactam antibiotics

New N-acylureido and N-acylthioureido derivatives of -lactam antibiotics were obtained by the reaction of 6-ureido and 6-thioureidopenicillanic and 7-thioreidodeacetoxycephalosporanic acids with acyl halides of carboxylic acids and benzoyl isocyanate. 6-Carbamoylhydroxypenicillanic acid, 6-thiocarbamoyl-hydroxypenicillanic acid, and its trichloroethyl ester were obtained by treatment of 6--hydroxypenicillanic acid and its trichloroethyl ester with isocyanatosilanes with subsequent hydrolysis of the N-silylcyanato groups.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 339–342, March, 1985.     

Die Umwandlung von Penicillinen in Cephalosporine. Modifikationen von Antibiotika, 3. Mitteilung

A new method for the degradation of the thiazolidine ring in penicillins is described. Penicillin V ( 8a ), penicillin G ( 8b ) and 6-t-butoxycarbonylaminopenicillanic acid ( 33 ) (BOC-6-APA) were converted via their acylazides and isocyanates ( 10 and 34 ) into 2,2,2-trichloroethyl urethanes ( 11 and 35 ). Reductive removal of the trichloroethoxycarbonyl groups in an aqueous medium gave the 3-hydroxy-penam-derivatives 13 and 36 . The structure and various reactions of these carbinolamides are discussed in detail. An oxidative radical fragmentation (using lead tetraacylates and light) followed by thermal treatment transformed the 3-hydroxy-penam-derivatives into the N-formyl-β-lactam-thio-enolethers 27 and 37 in which the formyl group could be replaced by hydrogen. Reactions of the β-lactam and thio-enolether functions are described. The BOC-derivative 37 can be transformed into the isomeric compound 3 , an intermediate in Woodward's total synthesis of cephalosporins.     

Ringerweiterung bei der Reaktion eines 1,3-Cyclohexandions mit Diphenylcyclopropenon

Ring Expansion during the Reaction of a 1,3-Cyclohexanedione with Diphenylcyclopropenone The reaction of 5,5-dimethyl-1,3-cyclohexanedione ( 1 ) in form of its Na-salt with diphenylcyclopropenone ( 2 ) in DMF yielded the bicyclic triketone 3 (58 %), the structure of which was deduced as an enolizeable bicyclo[5.2.0]nonane-β-diketone from spectral data and from the following reactions: hydrolysis or methanolysis of 3 cleaved the β-dicarbonyl moiety, thereby opening the 4-membered ring to yield the keto acid 9 or its methyl ester 10 . Methylation of 3 afforded the two enol ethers 4 and 5 . The ether 5 readily underwent a thermal electrocyclic ring opening to the monocyclic enol ether 8 , whereas the ether 4 was thermally stable. The same electrocylic ring opening (in boiling benzene) converted 3 (probably via 3b ) to the monocyclic triketone 7 , which was also the hydrolysis product of the ring-opened enol ether 8 . By heating 3 in DMF/H₂O, a partial (56 %) conversion to the lactone 6 took place. The tricyclic intermediate 11 was found useful to rationalize the ring expansion during the formation of 3 from 1 and 2 as well as the corresponding ring contraction during the conversion of 3 into 6 .     

Stereoselective Synthesis of Hydroxyethylene Dipeptide Isostere from Sugar

Regioselective opening of the aziridine ring in the carbohydrate-based precursor led to the stereoselective synthesis of N-Boc-O-benzyl-(4S,5S)-5-amino-4-hydroxy-6-phenylhexanoic acid methyl ester, the hydroxyethylene dipeptide isostere moiety of potent HIV-1 protease inhibitor.     

Development of hydrogenated ring‐opening metathesis polymers

New hydrogenated ring‐opening metathesis polymers with excellent thermal and optical properties were developed. These polymers were prepared by the ring‐opening metathesis polymerization of ester‐substituted tetracyclododecene monomers followed by the hydrogenation of the main‐chain double bond. The degree of hydrogenation was an important factor for the thermal stability of the polymers, and as complete hydrogenation as possible was necessary to obtain a thermally stable polymer. The completely hydrogenated ring‐opening polymer derived from 8‐methyl‐8‐methoxycarbonyl‐substituted monomer has a glass‐transition temperature of 171 °C and a 5% weight‐loss temperature of 446 °C. This polymer has excellent thermal and optical properties because of its bulky and unsymmetrical polycyclic structure in the main chain and is an alternative to glass or other transparent polymers such as poly(methyl methacrylate) and polycarbonate resin. This polymer has also been used in a wide variety of applications, such as optical lenses, optical disks, optical films, and optical fiber. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4661–4668, 2000     

Synthesis and biological activity of alkylidene-substituted cephems and penams

The condensation of tert-butyl esters of 3-methyl-7-oxoceph-3-em-4-carboxylic and 6-oxopenicillanic acids with a series of 2-oxoalkylidene(triphenyl)phosphoranes gave tert-butyl esters of new cephalosporin and penicillin analogs with an alkylidene substituent in the β-lactam ring. Most of these products were oxidized by meta-chloroperbenzoic acid to the corresponding sulfones. The cephemes and penams synthesized including the oxidized products displayed high cytotoxicity relative to cancer cells in vitro. Some of the alkylidene-substituted cephems as the free acids, similar to Tazobactam, inhibit the catalytic activity of Enterobacter cloacae penicillinase.     

Phenolic compounds from Scorzonera latifolia (Fisch. & Mey.) DC

A new 3-benzylphthalide, scorzoveratrin 4'-O-β-glucoside (1), together with the known 3-benzylphthalides, scorzoveratrin (2) and scorzoveratrozit (3), the caffeoyl derivatives, chlorogenic acid methyl ester (4), 4,5-dicaffeoylquinic acid (5), 4,5-dicaffeoylquinic acid methyl ester (6), 3,5-dicaffeoylquinic acid (7) and caffeic acid (8) were isolated from the subaerial parts of Scorzonera latifolia (Fisch. & Mey.) DC. All secondary metabolites were assigned using physicochemical and spectroscopic data. The known compounds 2-8 were isolated for the first time from this species.     

Enzymatic Synthesis of Amoxicillin via a One-pot Enzymatic Hydrolysis and Condensation Cascade Process in the Presence of Organic Co-solvents

A cascade reaction combining the enzymatic hydrolysis of Penicillin G potassium salt (PGK) with the kinetically controlled enzymatic coupling of in situ formed 6-aminopenicillanic acid (6-APA) with p-hydroxyphenylglycine methyl ester (D-HPGM) to give amoxicillin as the final product by using a single enzyme has been demonstrated successfully. Ethylene glycol (EG) was employed as a component of reaction buffer to improve the synthesis yield. Reaction parameters, including different cosolvents, EG content, the loading of immobilized penicillin G acylase (IPA), and reaction temperature and time were studied to evaluate their effects on the reaction. The best result of 55.2% yield was obtained from the reaction which was carried out in the mixed media containing 40% sodium dihydrogen phosphate buffer (apparent pH 6.0) and 60% EG (v/v), with the initial concentration 150 mM and 450 mM of PGK and D-HPGM, respectively, catalyzed by 50 IU/mL IPA at 25 °C for 10 h. The IPA could be recycled for nine batches without obviously losing of catalytic activity. The important strategy will have potential application in the β-lactam antibiotics industry due to the advantages of saving the effort of isolating 6-APA, reducing usual enzymatic steps and the industrial cost of amoxicillin synthesis.     

2, 4-Dimethyl -5 -nitrofuran -3 -carboxylic acid and its derivatives

It is found that 2, 4-dimethyl-5-nitrofuran-3-carboxylic acid and its methyl ester can give comparatively stable anionic groups, which are prepared electrochemically and investigated by EPR. Their lives (80–100 sec) are 4- 5 times greater than the lives of other anionic groups of the 5-nitrofuran series previously studied. Starting from 2, 4-dimethyl-5-nitrofuran-3-carboxylic acid and 2, 4-dimethylfuran-3-carboxylic acid, two new semisynthetic penicillins are prepared, with activities basically extending to Gram-positive microorganisms, including forms of staphylcocci resistant to benzylpenicillin. Introduction of the nitro group into the furan ring increases the stability of penicillin to acid 79-fold. Low toxicity penicillins are synthesized (LD₅₀ 1000–1500 mg/kg).     

Candida antarctica lipase B-catalyzed ring opening of 4-arylalkyl-substituted β-lactams

The Lipolase-catalyzed ring opening of racemic 4-benzyl- 3 and 4-phenylethyl-2-azetidinone 4 was performed with 0.5 equiv of H₂O in diisopropyl ether at 45 °C. The resulting (S)-β-amino acid 5 or 6 (ee ⩾ 87%) and (R)-β-lactam 7 or 8 (ee >99%) enantiomers could easily be separated. The ring opening of enantiomeric β-lactams with 18% aqueous HCl afforded the corresponding enantiopure β-amino acid hydrochlorides 9 and 10 (ee >99%).     

Synthetic transformations of higher terpenoids: XVII. Intramolecular cyclization of N-furfuryl amides of the labdane series

16-(Benzylaminomethyl)lambertianic acid methyl ester reacts with 2-methylprop-2-enoyl chloride to give unsaturated amide which readily undergoes intramolecular [4 + 2]-cycloaddition with formation of terpenoid derivatives of 10-oxa-3-azatricyclo[5.2.1.0^1,5]decenone. Acetylation of lambertianic acid methyl ester with acetic anhydride occurs preferentially at the 2-position of the furan ring and is accompanied by migration of the exocyclic double bond. Reductive amination of 16-acetyl-15,16-epoxylabda-8(9),13,14-triene and subsequent reaction of the resulting amine with 2-methylprop-2-enoyl chloride give intramolecular cyclization products in high yield without isolation of intermediate furfurylacryloyl derivative. Reactions of methyl 16-(benzylaminomethyl)-15,16-epoxylabda-8(9),13,14- and -8(17),13,14-trien-18-oates with maleic anhydride lead to the formation of the corresponding 10-oxa-3-azatricyclo[5.2.1.0^1,5]dec-8-ene-6-carboxylic acid derivatives as mixtures of diastereoisomers.     

The stereoselective synthesis of γ-lactam derivatives through N(1)-C(4) one carbon ring expansion of β-lactam derivatives

The base induced ring opening of β-lactam derivatives, 3, 5, 7, 9, 11 with LDA gave γ-lactam derivatives, 4, 6, 8, 10, 12 stereoselectively. The γ-lactam derivatives were formed stereoselectively depending on C-3 substituent of β-lactam derivatives.     

Plant-polyphenols and related compounds. A mass-spectrometric study of the trimethylsilyl derivatives of hydroxy- and/or methoxy-substituted cinnamic acids and of their methyl esters

The low resolution 70 eV mass spectra of the TMS (Trimethylsilyl) derivatives of eight naturally occurring hydroxy- and/or methoxycinnamic acids are presented in detail. The TMS derivatives studied are I, of o-coumaric acid; II, of m-coumaric acid; III, of p-coumaric acid; IV, of isoferulic acid; V, of ferulic acid; VI, of 3,4-dimethoxycinnamic acid; VII, of sinapic acid; VIII, of caffeic acid; Ia to Va, VIIa, of the corresponding methyl esters; and VIa, methyl 3,4-dimethoxycinnamate. The derivatives studied show a high degree of stability under conditions of electron-impact. The major fragmentation processes for the free acid TMS derivatives begin with methyl radical loss from either the ester or ring TMS group. The spectra of the methyl ester TMS derivatives have enabled the site of initial methyl loss to be determined. Accurate mass measurements and analysis of the second field-free region metastable peaks provide support for suggested fragmentation schemes. The spectra are sufficiently different to permit identification except between compounds IV and V (and IVa and Va) where the major fragmentation process involves a common ion, thought to be the silicon analogue of an acetonide.     

高效液相色谱-串联质谱法同时测定牛奶和奶粉中的青霉素类药物及其主要酶解代谢产物

建立了液相色谱-串联质谱法同时测定牛奶和奶粉中4种青霉素(青霉素G、青霉素V、阿莫西林、氨苄西林)及其4种 β-内酰胺酶酶解产物(青霉素G脱羧噻唑酸、青霉素V脱羧噻唑酸、阿莫西林脱羧噻唑酸、氨苄西林脱羧噻唑酸)残留的方法。样品采用乙腈-水提取,浓缩后经HLB柱净化,用液相色谱-串联质谱检测,外标法定量。结果表明,青霉素原药在4~200 μg/L,酶解产物在10~500 μg/L范围呈良好线性,线性相关系数均大于0.99;样品检出限为5~50 μg/kg(S/N≥3),定量限为8~100 μg/kg(S/N≥10);对牛奶和奶粉样品分别进行3个水平的加标回收实验(n=6),牛奶中青霉素及其酶解产物的平均回收率为83.48%~96.97%,相对标准偏差为3.86%~10.87%;奶粉中青霉素及其酶解产物的平均回收率为82.70%~95.14%,相对标准偏差为3.02%~9.81%。该方法稳定、可靠,适用于牛奶和奶粉中青霉素类药物及其酶解代谢产物的测定。     

A flow-injection system based on immobilized penicillinase and a linear pH-buffer for potentiometric determination of penicillin

Penicillin is determined in a flow-injection manifold by hydrolysis of the β-lactam ring by means of an on-line reactor containing immobilized penicillinase with detection of the produced acid by a glass electrode. The penicillin concentration is calculated as the difference in response between a sample passing through the enzyme reactor and a sample flowing directly to the glass electrode. The pH signal is made linearly dependent on the acid concentration by using a buffer mixture of constant buffer capacity and the reactor is designed so that hydrolysis of the penicillin is essentially complete in the reactor. The linear range is 0.1–15 mM penicillin and the sensitivity is 0.056 pH mM^?1. The sample throughput is 60 h^?1 and the relative standard deviation < 1%. The proposed method is primarily intended for the analysis of purified potassium salts of penicillins in pharmaceutical preparations.     

Ergoline derivatives—XIV : Synthesis of clavine alkaloids

The treatment of methyl lysergate with mercuric acetate in methanol yields, instead of the expected 10 - methoxy - 6 - methyl - ergoline - 8 β - carboxylic acid methyl ester (2), 10 - methoxy - 8,9 - didehydro - 6 - methyl - ergoline - 8 - carboxylic acid methyl ester (3), whose structure is demonstrated. From 3, penniclavine (14) and isosetoclavine (15) were prepared according to Scheme 1.