Synthesis of the peptide moiety of the jamaicamides

The jamaicamides, isolated from cyanobacterium Lyngbya majuscula in Jamaica, are unique mixed polyketide-peptides that are reported to be blockers of the sodium channels. The peptide moiety contains a pyrrolinone ring and a β-methoxy enone functionality. Herein, we report the stereoselective synthesis of the N-(Boc)₂-protected peptide moiety of the jamaicamides by utilizing Meldrum’s acid starting from l-alanine and N-Boc-β-alanine.     

Two substituted 2‐pyrrolin‐5‐ones: chains built from a single N—H...O hydrogen bond

In each of methyl 2‐methyl‐5‐oxo‐2‐pyrroline‐3‐carboxylate, C₇H₉NO₃, and 3‐acetyl‐2‐methyl‐2‐pyrrolin‐5‐one, C₇H₉NO₂, the pyrrolinone ring is planar. In each structure, molecules are linked into simple chains by way of a single N—H...O hydrogen bond.     

Recyclization of enaminocarbonyl and enaminothiocarbonyl imidazolidine and pyrroline derivatives

It was shown that recyclization of enaminocarbonyl compounds in acid media affords pyrrolinone derivatives. 2-Methylthio-4-oxopyrroline-1-oxide reacts with NaBH₄ exclusively at the carbonyl group- and with methylmagnesium iodide, at the nitrone group- with substitution of the methylthiol group for a methyl group.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 2, pp. 437–443, February, 1991.     

Synthesis of polypyrrolinones on solid support

[reaction: see text] An efficient, three-step iterative synthesis of polypyrrolinones has been achieved on solid support, setting the stage for the construction of a wide variety of libraries based on the pyrrolinone scaffold. Central to the approach is an effective end-game sequence featuring pyrrolinone ring construction with traceless release from the solid support.     

A novel diacetylenic bilirubin

An etiobilirubin‐IIβ analog with the central C(10) CH₂ group replaced by a diacetylene unit ( 1 ) was synthesized by base‐catalyzed condensation of bis‐[3‐methyl‐4‐ethyl‐5‐formylpyrrol‐2‐yl]‐diacetylene ( 3 ) with 3‐methyl‐4‐ethyl‐5‐p‐toluenesulfonyl‐2‐pyrrolinone ( 10 ). Diacetylenic rubin 1 is a dark red solid, giving orange solutions with uv‐visible absorption maxima near 460 nm.     

Enantioselective synthesis of antiinfluenza compound A-315675

Drug discovery efforts at Abbott Laboratories have led to the identification of influenza neuraminidase inhibitor A-315675 (1) as a candidate for development as an antiinfluenza drug. A convergent, stereoselective synthesis of this highly functionalized pyrrolidine is reported that utilizes pyrrolinone 2 as the key intermediate. The C5, C6 stereochemistry was established through a diastereoselective condensation of chiral imine compound 3 with silyloxypyrrole 4 to give pyrrolinone 2. The stereochemical outcome of this reaction depended critically on the choice of the imine functional group (FG), with tritylsulfenyl and (R)-toluenesulfinyl providing the desired products in good yields as crystalline intermediates. Conversion of pyrrolinone 2 into 1 was accomplished in seven subsequent steps, including Michael addition of cis-1-propenylcuprate at C4 and introduction of a cyano group as a carboxylic acid equivalent at C2.     

Architecturally diverse heterocycle formation by N-acyliminium ion initiated cyclization

Enaminoesters containing a tethered indole or aryl moiety on the amine react with substituted maleic anhydrides or acryloyl chlorides to provide pyrrolinone or dihydropyridone products, respectively. The indole-tethered dihydropyridones can be induced to undergo a one-pot cyclization whereas, the indole-tethered pyrrolinone intermediates are readily cyclized with HCl. The aryl-tethered pyrrolinones or dihydropyridones can be isolated and subsequently induced to cyclize with triflic acid. This methodology culminates in the synthesis of erythrane-like and other natural products that are readily amenable to combinatorial library production.     

Total synthesis of antibiotic althiomycin

Antibiotic althiomycin was totally synthesized from d-cysteine via the procedures of the coupling with sodium salt of pyrrolinone, hydroxymethylation, and the coupling with the thiazole part, successively.     

Total synthesis of cyclopiamide A and speradine E

Described is a total synthesis of the related alkaloids, cyclopiamide A and speradine E, via a unified strategy that also delivers the natural product aspergilline A. Key steps include metal-free conversion of a malonyl chloride and propargylamine to an intermediate pyrrolinone and a palladium catalyzed decarboxylation/aromatization sequence that delivers the requisite tetracyclic core.     

A second-generation synthesis of polypyrrolinone nonpeptidomimetics: prelude to the synthesis of polypyrrolinones on solid support

[reaction: see text] A second-generation asymmetric synthesis of polypyrrolinones (3) has been achieved exploiting scalemic alpha-aminolactones (1) as building blocks. Imine formation between an appropriate lactone (1) and aldehyde (2), followed in turn by pyrrolinone ring construction promoted by KHMDS in the presence of 18-crown-6 and modified Swern oxidation furnished pyrrolinone aldehyde 3. This iterative, efficient three-step protocol paves the way for the synthesis of polypyrrolinones on solid support.     

Design, synthesis, and binding affinities of pyrrolinone-based somatostatin mimetics

[structure: see text] Tetrapyrrolinone somatostatin (SRIF) mimetics (cf. 1), based on a heterochiral (D,L-mixed) pyrrolinone scaffold, were designed, synthesized, and evaluated for biological activity. The iterative synthetic sequence, incorporating the requisite functionalized coded and noncoded amino acid side chains, comprised a longest linear synthetic sequence of 23 steps. Binding affinities at two somatostatin receptor subtypes (hsst 4 and 5) reveal micromolar activity, demonstrating that the d,l-mixed pyrrolinone scaffold can be employed to generate functional mimetics of peptide beta-turns.     

Beiträge zur Chemie der Pyrrolpigmente, 20. Mitt.: Untersuchungen über das Deprotonierungsgleichgewicht und die Bildung von Metallkomplexen von Gallenpigment-Partialstrukturen

By spectrophotometric measurements in the systemDMSO/H₂O/Me ₄NOH pK _a-values for several model compounds representing bile pigment partial structures were established. The acidic protons of pyrrole and lactame type nitrogen atoms are removed by bases governed by the electronic properties of the substituents on these ring systems. The pK _a-values for both types lie in the same region. In the pyrromethenones the lower one corresponds to the lactame type NH as was deduced by comparison with specifically methylated derivatives.The complexation of these ligands is determined by the possibility of removing an acidic proton and achieving a chelate structure by means of an adjacent pyrrolinone type nitrogen atom. Complexes are favoured in the series pyrromethenes > lactim ethers > pyrromethenones. With the latter there are two possibilities: one observed with BF₂-chelation where the lactime form becomes stabilized, the other one with zink where both acidic centers are involved in the bonding.

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19. Mitt.:H. Falk, A. Leodolter undG. Schade, Mh. Chem.109, 183 (1978).     

Synthesis and Reactions of New Dithiolopyrroles

The title compounds were prepared starting from pyrrolinone 4 . Nucleophilic‐displacement and ring‐closure reactions yielded the dithiolopyrrole 5a , which formed salts with electrophiles ( 7, 8 ) as well as with bases. The crystal structure of 5a was determined. Oxidation of the dithioles 5a and 6a led to S(2)‐oxides ( 10a, 11a ) and the corresponding S(2)‐dioxides ( 10b, 11b ) depending on reaction conditions. The thiosulfinate 10a was converted by a ring‐opening/ring‐closure reaction sequence to the bicyclic sulfinamide 12 . The oxidative addition reactions of [Pt(η²‐C₂H₄) (PPh₃)₂] ( 14 ) with the disulfides 5a and 13 led to the dithiolatoplatinum(II) complexes 15 and 16 , respectively. Complex 16 was characterized structurally. The sulfenato‐thiolato complex 17 was synthesized via reaction of 14 with the thiosulfinate 10a . The thiosulfonato Pt^II complex 18 was prepared by an oxidative insertion of Pt⁰ into the C? S bond of the corresponding thiosulfonate 10b . Furthermore, complex 18 was characterized by single‐crystal X‐ray‐diffraction studies.     

Ethylcyclopentane ring opening reaction over PtGe/Al2O3 catalysts prepared by controlled surface reaction

Platinum-germanium catalysts supported on a non-acidic Al₂O₃ have been prepared by adding Ge in amounts corresponding nominally to 1/8 (PtGe1/8/Al₂O₃); 1/2 (PtGe1/2/Al₂O₃); 1 (PtGe1/Al₂O₃) and 2 (PtGe2/Al₂O₃) monolayers by controlled surface reaction of Ge(n-C₄H₉)₄ to Pt/Al₂O₃. These catalysts were characterized by electron microscopy (TEM), FTIR of CO adsorption and H₂ chemisorption. The ring opening of ethylcyclopentane (ECP) was studied as a test reaction between 543 and 633 K. PtGe1/8/Al₂O₃ catalyst produced the most ring opening products (ROP) in the whole temperature range. A good agreement with statistical values of ROP was observed at low temperature, but at higher temperature, the opening became selective, producing mostly heptane. Bimetallic catalysts PtGe1/Al₂O₃ and PtGe2/Al₂O₃ led to a nonselective hydrogenolysis, similar to the monometallic platinum catalyst Pt/Al₂O₃. The catalysts PtGe1/Al₂O₃ and PtGe2/Al₂O₃ produced ROP with the lowest selectivity; instead, much aromatics and fragments were formed, in increasing amounts above 600 K.     

Substitution of 3H-furan-2-ones in amination and hydroamination reactions

The amination and hydroatnination of 5-alkyl-3H-furan-2-ones and their 3-benzylidene- and 3 formyl-derivatives were studied. The characteristics of the reactions, the requirements for the nature of the nucleophilic reagents, and the reaction conditions leading to the destruction of the furan ring and recyclization to pyrrolidinone and pyrrolinone structures are indicated.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 349–352, March, 1994.     

Synthesis of amino derivatives of 5-aralkylidene-3-pyrrolin-2-ones

Preparation of some derivatives of 5-aralkylidene-3-pyrrolin-2-ones is reported. Compounds with an amino group on the phenyl ring at the 3-position of the pyrrolinone ring showed suitable properties as potential UV-A filters. Some of the compounds were quaternarized to enhance their solubility in aqueous solvents.     

New method for synthesis of 3-pyrrolin-2-one derivatives

We propose a method for synthesis of derivatives of pyrrolinone by reaction of the methyl ester of 3-substituted 2-oxo-3-pentonoic acid with primary amines or acetylhydrazine.Institute of Organic Chemistry, National Academy of Sciences of the Armenian Republic, Yerevan 375094. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1345–1350, October, 1994. Original article submitted July 4, 1994.     

Hydrolytic Heterocyclization of the 1,1,2,3,3‐Pentacyanopropene Salts

Salts of 5‐amino‐4‐cyano‐3‐dicyanomethylene‐2‐pyrrolinone are formed by action of dilute aqueous solutions of alkalis on pentacyanopropenide‐anion salts. These cyclic salts are transformed to 2,6‐diamino‐3,5‐dicyanoisonicotinates by subsequent action of alkalis.     

Short Synthesis of Pulchellalactam

tert‐Butyl 4‐methyl‐2‐oxo‐2,5‐dihydro‐1H‐pyrrole‐1‐carboxylate 4 was synthesized by a short two‐step procedure: regioselective 1,3‐dipolar diazomethane cycloaddition to N‐Boc‐pyrrolinone 2 and thermolysis of the adduct. The compound 4 could be converted in one step into pulchellalactam.     

Novel heterocycles derived from 3-acyloxy- and 3-acetamidoquinuclidines

New quinuclidine derivatives with 3-spiro annelated oxathioline, furanone, and pyrrolinone heterocycles have been synthesized from 3-mesyloxy-, 3-acetoxy-, and 3-acetamidoquinuclidine-3-carbonitrile, respectively, by treatment with base. Treatment of 3-acetamidoquinuclidine-3-carbonitrile ( 3 ) with potassium hydride resulted in decyanation whereas alkyllithium reagents attacked the cyano group in 3 to produce the corresponding imines. Oxidative cyclization of the N-benzylated derivative of 3 with palladium acetate gave the tetracyclic compound 5-acetyl-1,4-ethano-1,2,3,4,5,6-hexahydrobenzo[c]-1,5-naphthyridine.