A Convenient Synthesis of 1-Ether-2-acylamido-2-deoxy-sn-glycerophospholipids

A series of 1 -ether-sn-2-acylamidoglycerophospholipids, bearing different polar heads in sn-3-position such as phosphoglycol, -serine, -ethanolamine or -choline, have been prepared. Except for the choline derivative which was synthesized from a ß-carbamate alcohol derivative, the remaining compounds were obtained from ß-amidoalcohols.     

Research on 2- acyl-3-aminobenzofurans II. Synthesis of heterocyclic systems from 2-acyl-3-aminobenzofuran derivatives

Various condensed heterocyclic systems were obtained from 2-acyl-3-aminobenzofuran derivatives.See [1] for communication I.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1319–1321, October, 1975.     

Synthesis of chiral 2-oxazolidinones, 2-oxazolines, and their analogs

Chiral five-membered ring 2-oxazolidinones and six-membered ring 1,3-oxazinan-2-ones are synthesized from the corresponding amino alcohols with complete inversion or retention of stereochemistry. Chiral 5-substituted 2-oxazolines and 6-substituted 2-oxazines are also synthesized from the same starting materials with inversion of stereochemistry through an intramolecular S_N2 reaction. These compounds are useful intermediates in organic synthesis and crucial building blocks for many pharmaceutical compounds.     

Synthesis of 3-acyl-1-alkyl-2-alkylseleno-1-cyclobutene using alkyneselenolate

The reaction of lithium alkyneselenolate with alpha,beta-unsaturated ketone and then alkyl or acyl halide afforded 3-acyl-1-alkyl-2-alkylseleno-1-cyclobutene. The structure of the cyclobutene was elucidated by IR, MS, (1)H, (13)C, and (77)Se NMR, COSY, HMQC, and HMBC data and X-ray analysis.     

Synthesis of 1-acyl-5-aryl biurets

Fourteen new 1-acyl-5-aryl biurets were synthesized by the reaction of aryl ureas with acylisocynantes. The latter was obtained from acyl chloride and lead cyanate in dichloromethane, using pyridine as catalyst. The structures of compounds 3a-n were confirmed by IR,1H NMR and MS spectra.     

Synthesis of 1-alkyl(aralkyl)-4-acyl-2-piperazinones

1-Alkyl(aralkyl)-4-acyl-2-piperazinones are formed in high yields during selective acylation of N-monosubstituted ethylenediamines by benzoyl and cyclohexylcarbonyl chlorides in the presence of pyridine hydrochloride and treatment of the reaction products with chloroacetyl chloride in the presence of potassium tert-butylate.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 514–517, April, 1986.     

Synthesis and stereochemistry of 1-acyl-2-alkyl-1,2,3,4-tetrahydroquinoline-3,4-epoxides

Summary Analogous to the recently described synthesis of Reissert epoxides the treatment of 1-acyl-2-alkyl-1,2-dihydroquinolines withm-chloroperoxybenzoic acid gave diasteromeric pure epoxides which are stable in crystalline state, but reactive in solution versus nucleophiles. Acting as useful intermediates to stereocontrolled functionalized 1,2,3,4-tetrahydroquinolines an X-ray analysis was performed to confirm the relative stereochemistry of the epoxides.

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Synthese und Stereochemie von 1-Acyl-2-alkyl-1,2,3,4-tetrahydrochinolin-3,4-epoxiden

Zusammenfassung Analog zu der kürzlich beschriebenen Synthese von Reissert-Epoxiden liefern 1-Acyl-2-alkyl-1,2-dihydrochinoline bei Behandlung mitm-Chlorperbenzoesäure diastereomerenreine Epoxide, die sich als Festsubstanzen außerordentlich stabil, in Lösung aber reaktiv gegenüber Nucleophilen erweisen. Da sie wertvolle Ausgangsverbindungen zu 1,2,3,4-substituierten Tetrahydrochinolinen mit definierter relativer Konfiguration darstellen, wurde die Stereochemie der Epoxide mittels Röntgenstrukturanalyse abgesichert.

     

Triazole antifungals. II. Synthesis and antifungal activities of 3-acyl-4-methyloxazolidine derivatives

Triazole compounds with an oxazolidine ring were designed and synthesized as a potential inhibitor of the fungal cytochrome P450 14 alpha-demethylase. In testing for antifungal activity against a mouse systemic Candida albicans infection, (4R,5R)-3-acyl-4-methyloxazolidine derivatives 4 exhibited remarkably high efficacy after oral or parenteral dosing. The potent activity of 4 is hypothesized to be a consequence of a structural similarity between 4 and lanosterol, a target molecule of the cytochrome P450 14 alpha-demethylase. Highly stereoselective synthesis of these oxazolidines is also described.     

Synthesis of novel lysophosphatidylcholine analogues using serine as chiral template

Four novel lysophosphatidylcholine (lysoPC) analogues, (S)-N-stearoyl-O-phosphocholineserine methyl ester [(S)-1a], (R)-1-lyso-2-stearoylamino-2-deoxy-sn-glycero-3-phosphatidylcholine [(R)-2a], (R)-N-stearoyl-O-phosphocholineserine methyl ester [(R)-1b], and (S)-1-lyso-2-stearoylamino-2-deoxy-sn-glycero-3-phosphatidylcholine [(S)-2b], were synthesized starting from serine as a chiral template. These synthetic compounds exhibited greatly enhanced hyphal transition inhibitory activity in Candida as compared to the natural lysoPC.     

Synthesis of 2-acyl-3-methylthiofurans from 3-methylthio-2-pentene-1,5-dione enolates

2-Acyl-3-methylthiofurans 3 are obtained in fair yields from 3-methylthio-2-pentene-1,5-dione enolates 1 by reaction with iodine. In a similar reaction 1-phenyl-3-methylthio-4-nitro-2-buten-1-one gave 3-methylthio-2-nitro-5-phenylfuran 11. In the crystalline state the 2-benzoyl-3-methylthio-5-phenylfuran 3b showed a non-bonded sulfur-oxygen interaction as inferred from an X-ray diffraction determination, with a S····O distance of 2.871(5)Å.     

Total synthesis of thienamycin analogs. II Synthesis of 2-alkyl and 2-aryl thienamycin nuclei

A new general synthesis leading to 2-alkyl and 2-aryl-1-carba-2-penem-3-carboxylic acids involves the preparation of a key thiolester intermediate 3. This is reacted with Me₂CuLi or (C₆H₅)₂MgCuX to give the corresponding methyl or phenyl ketone which undergoes a Wittig reaction to give the desired penems, which can be deblocked photolytically or by hydrogenolysis to give acids with good antibacterial activity.     

Rearrangements of 1-oxa-2-azoles. 7. Synthesis and heterocyclization of 3-acyl-1,2,4-oxadiazole oxime

The reaction of 1,2,4-oxadiazole-3-carbonitrile oxide with 2-(ethoxycarbonylmethylene)imidazolidine gives an acyclic addition product, which cyclizes in basic medium into an isoxazole derivative, while in an acid medium it rearranges into an aminofurazan derivative.For Communication 6, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1121–1122, August, 1991.     

Synthesis and synthetic utility of 1-acyl-2-alkyl-4-trimethylstannyl-1,2-dihydropyridines

1-Acyl-2-alkyl-1,2-dihydropyridines were prepared from 4-trimethylstannylpyridine and Grignard reagents. This methodology was utilized in the synthesis of N-methyl-2-azatricyclo[5.3.1.0]undecane.     

Benzothiazoline derivatives. II. Preparation of N-substituted derivatives of 2-benzothiazolinethione by thiation of the 2-oxo analogs

Thuiation of the benzoate and acetate esters of 3-(2-hydroxyethyl)-2-benzothiazolinone (Ig) gave the corresponding thiones. The benzoate was then deblocked to yield 3-(2-hydroxyethyl)-2-benzothiazolinethione (Ik), a compound not accessible by direct addition or substitution. Attempts to introduce a chlorine (or bromine) atom in place of the hydroxy 1 group in the latter compound or its S-isomer, 2-(2-hydroxyethylthio)benzothiazole (11a), gave 2,3-dihydrothiazolo-[2,3-b ] benzothiazolium chloride (or bromide) (IIIa or b). The latter compound undergoes dihydrothiazolo ring opening when treated with sodium hydroxide or sodium sulfide to give bis[2-(2-benzolhiazolinon-,3-yl)ethyl]disulfide (IVc) or bis[2-(2-benzothiazolinethion-3-yl)ethyl] disulfide (lVb),respectively. 2-Benzothiazolinethione reacted with ethylenimine and with N-phenylethylenimine to give S-substituted derivatives. Addition to vinyl n-butyl ether gave the expected N-substituted derivative, which was found to undergo removal of the butyoxyethyl group when subjected to conventional conditions for ether cleavage.     

New chiral acyclic analogs of 2′-deoxynucleosides

Convenient methods for the synthesis of chiral 2,3-seco-2-deoxynucleosides were developed. An isopropylidene protective group was used to block the 3,5-hydroxy groups in 2,3-seco-uridine. Conversion of the hydroxymethyl group to a methyl group was accomplished by chlorination with a mixture of CCl₄ and Ph₃P with subsequent reduction with n-Bu₃SnH. 2,3-seco-2-Deoxyuridine was obtained after deacetonation. The (S) enantiomer was similarly synthesized starting from 1-(-D-arabinofuranosyl)uracil. 3-O-tert-Butyldimethylsilyl-5-O-(p-monomethoxytrityl)-2,3-seco-2-deoxyuridine, which has optically active centers at C₍₁₎ and C₍₄₎, was also synthesized.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 822–826, June, 1988.The authors thank Professor M. Ya. Karpeiskii for his constant interest in this research.     

Rh(II)-Catalysed reactions of 2H-azirines with ethyl 2-acyl-2-diazoacetates. Synthesis of novel photochromic oxazines

Photochromic non-fused 2H-1,4-oxazines are synthesised by a Rh₂(OAc)₄-catalysed reaction of 2Н-azirines with ethyl 2-acyl-2-diazoacetates. The reaction proceeds via the formation of an azirinium ylide which undergoes ring-opening to a 2-azadiene followed by 1,6-electrocyclisation.     

Acyclic analogs of nucleosides. Synthesis of chiral 1,5-dihydroxy-4-methyl-3-oxapent-2-yl derivatives of uracil

A convenient method has been developed for the synthesis of optically active 1-[1,5-dihydroxy-4-(R)-methyl-3-oxapent-2(R and S)-yl]uracils. 5-Deoxyuridine is obtained from 2,3-O-isopropylideneuridine, and its periodate oxidation followed by reduction with sodium tetrahydroborate leads to the desired 4(R), 2(R)-isomer. The acetonide of -uridine is converted into the 4(R),2(S)-isomer analogously.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 91–94, January, 1988.The authors thank Prof. M. Ya. Karpeiskii for constant interest in this work.