Amino Lactones Research Articles

A Novel Potassium-Binding Hydrolysis Product of Ascidiacyclamide: A Cyclic Octapeptide Isolated from the Ascidian Lissoclinum patella.

A new octapeptide has been isolated and characterized as its potassium complex from acidic aqueous methanol solutions of ascidiacyclamide, a cyclic peptide isolated from the ascidian Lissoclinum patella. Crystals suitable for X-ray structure determination were orthorhombic, space group P2(1)2(1)2(1), with a = 15.442(3) Å, b = 36.167(1) Å, c = 9.567(3) Å, V = 5343(2) Å(3), Z = 4, and R = 0.069. The structure consists of the macrocyclic cation, three perchlorate anions, and two water molecules. The macrocyclic ring of ascidiacyclamide remains intact, but two oxazoline rings have been opened to form two amino lactones, with the amine protonated. A potassium ion is bound to the N atoms of the thiazole rings (K(1).N(1), 2.47(2) Å; K(1).N(5), 2.50(2) Å) and to the adjacent O (amide) atoms (K(1).O(1), 2.34(1) Å; K(1).O(5), 2.34(1) Å). Two perchlorate anions, located on either side of the plane of the macrocyclic ring, are weakly associated with the potassium cation (K(1).O(10), 2.72(3) Å; K(1).O(16), 2.48(3) Å). This cyclic octapeptide reacts with copper(II) to give a purple solution (lambda(max) 590 nm).

2,6-Di-O-pentyl-3-O-propionyl-γ-cyclodextrin as an enantiomeric stationary phase for capillary gas chromatography

2,6-Di-O-pentyl-3-O-propionyl-γ-cyclodextrin has been synthesized and used for enantiomer separation in capillary gas chromatography. Experimental results showed that the stationary phase has good enantiomer selectivity toward amino acids, amines, alcohols, diols, epoxides, and lactones,etc. 2,6-Di-O-pentyl-3-O-propionyl-γ-cyclodextrin has good thermal stability: the highest recommended temperature isca 170°C.

Synthesis of a peptidyl 2,2-difluoro-4-phenylbutyl ketone and its evaluation as an inhibitor of interleukin-1β converting enzyme.

An efficient way of preparing the peptidyl 2,2,-difluoro-4-phenylbutyl ketone ( 1) is described that utilizes condensation of the 2,2-difluoro-5-phenylpentanoyl chloride ( 6) with the oxazolone derivative 9, followed by isomerization and decarboxylation to provide the difluoro compound 12. Treatment of the ketone 12 with NaBH 4 followed by 6% Na/Hg afforded the amino lactone 14. This amino lactone was coupled to N-(3-phenylpropionyl)valylalanine to provide the lactone 15. Hydrolysis of the lactone 15 and oxidation of the resulting alcohol afforded the target compound 1 in good yield.

Tetrahydrofurane und γ‐Lactone, VI. Optisch aktive N‐Boc‐δ‐Amino‐γ‐lactone aus Cyclooctin und Furan

Tetrahydrofurans and γ‐Lactones, VI. – Optically Active N‐Boc‐δ‐Amino‐γ‐lactones from Cyclooctyne and FuranThe stereoselective synthesis of the title compounds (−)‐(2′R,8S)‐2b and (+)‐(2′S,8R)‐2b from (2′R,8R)1a and (2′S,8S)‐1a is described. The unprotected amino lactone 2c undergoes rearrangement to the γ‐hydroxy‐δ‐lactam 3a by treatment with hydrogen chloride.

Intramolecular photoreactions of 2-formylbenzamides and 2-formylbenzylamines

Irradiation of 2-formylbenzylamine 7 in the presence of fumarates affords adducts corresponding to trapping of quinodimethane intermediate 9, while photolysis of 2-formylbenzamides leads to amino lactones 16.

Stereoselective synthesis of sperabillins and related compounds

Baker's yeast reduction of methyl (4S)-4-(tert-butoxycarbonylamino)-3-oxopentanoate 6 stereoselectively afforded methyl (3R,4S)-erythro-4-Boc-amino-3-hydroxypentanoate 7, which was converted into the erythro keto δ-lactone 3a in three steps. The threo keto δ-lactones 3b–c were diastereoselectively prepared by cyclocondensation of N-Boc D- and L-alaninal 4 with 1 -methoxy-1, 3-bis(trimethylsiloxy)buta-1,3-diene 9 in the presence of a catalytic amount of tin(II) chloride. Recluctive amination of the keto lactones 3 using 5% platinum on carbon as catalyst in an acidic medium stereoselectively afforded the N-protected 3,6-diamino-5-hydroxyheptanoic acid lactones 1 with 3,5-anti stereochemistry. These were transformed into the enantiomerically pure sperabillin 17 and negamycin 20 derivatives in good yields. The configuration of sperabillin B and D was determined to be (3R,5R,6R) by comparison of the synthetic amino lactone 1e with a degradation product of sperabillin B and by the successful transformation of the synthetic amino lactone 1b into sperabillin D.

Separation of enantiomers in thin-layer chromatography

Up to now in thin-layer chromatography a series of retention mechanisms for the determination of enantiomeric compositions have been applied. Subject of this paper is a corresponding survey with a focal point on ligand exchange chromatography. In connection with this retention mechanism most successfully used in TLC for the separation of optical antipodes, some additional findings of the authors are included. Retention mechanisms in question are: - Formation of inclusion complexes within the cavities of cyclodextrins. Substance classes separated by this system are e.g. dansyl amino acids or metallocenes. - Interaction with so-called “brush type” phases. In this case, chiral groups with π-acceptor of π-donor properties are chemically or physically bonded to an aminomodified silica gel matrix. Chiral compounds, like aromatic alcohols, were separated on these stationary phases. - Differences in retention of diastereomers formed previously or during the chromatographic process on an achiral stationary phase. Some examples for the manifold applicability of this principle are the separation of chiral amines from biological matrices, hydroxy-fatty acids, and amino acids. - Selective interactions with the helical structures of cellulose or cellulose triacetate. Referring to this technique, separations of several amino acids and of the analgesic agent Oxidanac in the R-and S-species are described. - Enantioselective ligand exchange, based on reversed phase silica gels impregnated with copper salts and optically active amino acid derivatives. In thin-layer chromatography this is the most important principle used mainly for the separation of racemic mixtures of free amino acids and amino acid derivatives. The recently developed HPTLC pre-coated plate CHIR with concentrating zone is also based on this retention mechanism. Aside from the applications mentioned above, dipeptides, hydroxy-carboxylic acids, α-halogenated carboxylic acids, amino lactones, and thiazolidine derivatives have been separated on this plate up to now. Furthermore, this new pre-coated layer is particularly suitable for an optical in situ evaluation and quantitative determinations of optical antipodes.

A New Synthesis of 5-Phenyl-2,3-dihydro- and 2,3,4,5-Tetrahydro-1H-2-benzazepin-1-ones

It was shown that 3-phenyl-3-(2-aminoethyl)phthalide (6, R = H) and its N-methyl analog (6, R = CH3) existed in the amino lactone form in solution at room temperature. In the absence of solvents, however, these compounds underwent a spontaneous transformation into the 5-phenyl-2,3,4,5-tetrahydro-1H-2-benzazepin-1-ones (8, R = H, CH3) which suffered dehydration in sulfuric acid with the formation of 5-phenyl-2,3-dihydro-1H-2-benzazepin-1-ones (9, R = H, CH3).This benzazepine synthesis can be considered to be analogous to the known (12–15) conversion of 1-aminomethylphthalides (11) to 4-hydroxy-3,4-dihydroisocarbostyrils (13).

The synthesis of homoprotoberberines

Three approaches to the homoprotoberberines have been developed. Mannich condensation of amine 7 with formaldehyde gave homoprotoberberine 9. In the homophthalide approach, treatment of amino lactones 13 and 14 with base gave lactam alcohols 15 and 16, which could in turn be converted to amino alcohols 18 and 19. Furthermore, lactam alcohols 15 and 16 underwent catalytic hydrogenolysis to lactam 20. Reduction of 20 with LAH furnished homoprotoberberine base 21. In the Dieckmann sequence, cyclization of diester 24 afforded α-amino ketone 25 which was readily reduced to the homoprotoberberine alcohol 26. The homoprotoberberine bases prepared were found to be cis B/C fused. Homoprotoberberines unsubstituted at C-9 undergo catalytic hydrogenolysis with cleavage of the N 7C 8 bond.