Synthesis,stereochemical characterisation and absolute configuration of enantiomerically pure complexes of sexidentate ligands

Summary The optically active sexidentate Schiff bases [H₃ L ⁵] and [H₃ L ⁶] were prepared from tris[(S)-2-aminopropyl]amine and 5-chlor- and 5-isopropylsalicylaldehyde, respectively. Reaction of rhodium trichloride with [H₃ L ⁶] gave an enantiomerically pure [RhL ⁶] complex with an absolute configuration of for the octahedral arrangement. The chiroptical properties are given.

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Synthese, stereochemische Charakterisierung und Absolutkonfiguration enantiomerenreiner Komplexe sechszähniger Liganden (Kurze Mitt.)

Zusammenfassung Ausgehend von Tris[(S)-2-aminopropyl]amin und 5-Chlor- beziehungsweise 5-Isopropylsalicylaldehyd wurden die optisch aktiven sechszähnigen Schiffschen Basen [H₃ L ⁵] und [H₃ L ⁶] hergestellt. Die Umsetzung von Rhodiumtrichlorid mit [H₃ L ⁶] ergab einen enantiomerenreinen Komplex [RhL ⁶] mit einer Absolutkonfiguration von für die oktaedrische Anordnung des Liganden. Die chiroptischen Eigenschaften werden angegeben.

     

Synthesis of enantiomerically pure (E)-1,1,3,3,6,6-hexamethyl-1-sila-4-cycloheptene and its absolute configuration

The title compound 1, a highly strained (E)-cycloalkene, was prepared in enantiomerically pure form from the corresponding trans-1,2-diol 4 via the thionocarbonate 5. The racemic 4 was separated by enantioselective HPLC on an amylose tris(3,5-dimethylphenylcarbamate) column. The absolute configuration of 1 was determined by circular dichroism spectroscopy in connection with theoretical calculations; the (+)-enantiomer has the (S)- and the (−)-enantiomer the (R)-configuration.     

First preparation of enantiomerically pure sibutramine and its major metabolite,and determination of their absolute configuration by single crystal X-ray analysis

Racemic sibutramine was resolved with dibenzoyl-d-tartaric acid, and the absolute stereochemistry of sibutramine was determined by single crystal X-ray crystallography of its dibenzoyl d-tartrate. The major active metabolite (desmethylsibutramine) was obtained by demethylation of sibutramine with DEAD. Enantiomeric purity of sibutramine was determined by HPLC on an Ultron ES-OVM column.     

Synthesis and determination of the absolute configuration of chiral tetracosanaphthalenes

Tetracosanaphthalenes with diethylaminocarbonylmethoxy side chains were constructed by bottom-up synthesis, and their absolute configurations were determined by an exciton chirality method.     

Synthesis of chiral isoquinuclidines and determination of their absolute configuration

A route to 1,2-dihydropyridines N¹-substituted with chiral auxiliaries has been developed starting from commercially available chiral amines. Cycloaddition between these dihydropyridines and methyl acrylate gave, in moderate d.e., isoquinuclidines of good enantiomeric purity whose absolute configuration has been established.     

Stereoselective synthesis of kurzilactone and determination of its absolute configuration

Both (5S,7S)- and (5R,7S)-isomers of kurzilactone were synthesized from a ‘chiral epoxy-aldehyde synthon’ through the coupling of an acyl anion equivalent and the dianion of acetoacetate, followed by formation of the Kawa-type lactone by cyclization and elimination. Comparing the spectral data of the synthesized and naturally occurring kurzilactone, the C(5)- and C(7)-stereogenic centers of the natural kurzilactone was assigned a corrected anti-relationship with (5R,7S)-absolute configuration.     

Synthesis of the saccharomicin fucose-aglycon conjugate and determination of absolute configuration

[reaction: see text] Schmidt glycosylation of the appropriately protected 3,4-dihydroxycinnamate methyl ester with 2,3,4-triacetoxyfucopyranosyltrichloroacetimidate gives aryl glycoside in high yield and diastereoselectivity. 2-Sulfation of fucose, installation of taurine, and global deprotection of the remaining protecting groups affords the fucose-aglycon conjugate of saccharomicin. This synthesis which arises from L-fucose also establishes the absolute configuration of the reducing terminus of the saccharomicin oligosaccharide.     

Synthesis of enantiomerically pure 3-aminochroman derivatives

Enantiomerically pure (3R)-amino-5-methoxy-3,4-dihydro-2H-1-benzopyran was successfully synthesised in nine steps starting from l-serine. The same synthetic pathway was used to prepare the (3S)-aminochroman derivative starting from d-serine. The enantiomeric purity of the final aminochroman derivatives was determined by capillary electrophoresis using β-cyclodextrin as the chiral selector.     

A route to enantiomerically pure 5-(2′-hydroxyethyl)cyclopent-2-en-1-ol and its absolute configuration by Mosher esters

The (±)-5-(2′-hydroxyethyl)cyclopent-2-en-1-ol 1 was prepared in a one-pot procedure, and was resolved using lipase AK and vinyl acetate with high ee. This provides a readily available chiral synthon for the synthesis of a wide variety of biologically interesting molecules. Further, the absolute configuration of diol 1 was confirmed directly by the Mosher ester method.     

Synthesis of eupomatilone-6 and assignment of its absolute configuration

[Reaction: see text]. The Zn-mediated Barbier reaction of the biarylaldehyde 8 with crotyl bromide followed by hydroboration and oxidation provided the gamma-butyrolactones 4 and 5. The stereoselective installation of methyl group at C-3 by using LiHMDS and MeI completed the synthesis of racemic eupomatilone-6 (2) and its diastereomer 3. The spectroscopic data of 2 was in full agreement with reported spectra of natural product, thus confirming the revised relative configuration of eupomatilone-6. Similarly, an optically active (3R,4R,5S)-isomer of eupomatilone-6 (23) was prepared in which the aldol reaction with thiazolidinethione as a chiral auxiliary was employed as a key step. On the basis of the spectroscopic data and optical rotation values of 23, the absolute configuration of eupomatilone-6 was proposed.     

Total synthesis of colombiasin A and determination of its absolute configuration

The total synthesis of the recently reported marine natural product colombiasin A (1) and determination of its absolute configuration are reported. Two Diels-Alder cycloadditions and a palladium-catalyzed rearrangement are employed as key reactions to construct the tetracyclic framework of the target molecule. The enantioselective synthesis of colombiasin A utilizes Mikami's [(S)-BINOL-TiCl2] catalyst to asymmetrically introduce the first chiral center during the initial Diels-Alder reaction and, in conjunction with X-ray crystallographic analysis of a bromine containing derivative, led to the assignment of the absolute configuration of the natural product.     

Synthesis and determination of the absolute configuration of the macrodiolide (+)-conglobatin

(+)-Conglobatin is synthesized from (-)-(2S,4R)-2.4-dimethyl glutaric acid half-ester in 15 steps (total yield 4.4%). The synthesis proves the sense of chirality of the natural (-)-conglobatin to be opposite to the one previously assigned.     

Synthesis of novel enantiomerically pure tetra-carbohydrazide cyclophane macrocycles

A total of twelve novel enantiomerically pure tetra-carbohydrazide cyclophane macrocycles have been synthesised in quantitative yields by reacting chiral (4R,5R)- and (4S,5S)-1,3-dioxolane-4,5-dicarbohydrazides with aromatic bis-aldehydes in a [2 + 2]-cyclocondensation reaction. The compounds show a dynamic behaviour in solution, which has been rationalized in terms of an unprecedented conformational interconversion between two conformers one stabilised by intramolecular hydrogen bonding and π-π stacking interactions.     

Synthesis of enantiomerically pure vinylcyclopropylboronic esters via cross-metathesis

The potent antibiotic ambruticin caused us to investigate two new aspects of cyclopropylboronic ester chemistry: we established the analytical basics for all 1,2,3-trisubstituted diastereoisomers as well as the cross-metathesis as a tool to synthesise vinylcyclopropylboronic esters.     

Synthesis of 1-deoxy-D-galactohomonojirimycin via enantiomerically pure allenylstannanes

1-Deoxy-D-galactohomonojirimycin was synthesized in seven steps from optically pure allenylstannane 4 and L-lactate-derived aldehyde 5 in 48% overall yield. The key step was the Lewis acid catalyzed reaction of 4 and 5 to give the syn-amino alcohol in excellent yield and very high diastereoselectivity.     

The first total synthesis of putaminoxin and determination of its absolute configuration

Asymmetric synthesis of putaminoxin, a phytotoxic macrolide from the cultured dinoflagellate Amphidinium sp., has been accomplished. Absolute configuration of putaminoxin was concluded to be 1 from comparison of the NMR data and [α]_D values of synthetic and natural putaminoxin.     

Synthesis of enantiomerically pure cis- and trans-cyclopentane analogues of phenylalanine

For the first time, all stereoisomers of 1-amino-2-phenylcyclopentanecarboxylic acid—c₅Phe—have been synthesised. A Strecker reaction on 2-phenylcyclopentanone and further transformations of each amino nitrile into the amino acid provides cis-c₅Phe and trans-c₅Phe with high efficiency. A divergent synthetic route was then developed to obtain the target compounds cis- and trans-c₅Phe in their racemic form. The preparation of the final enantiomerically pure amino acids and their corresponding N-protected derivatives was also achieved by HPLC resolution of one of the intermediates using a cellulose-derived chiral stationary phase. The relative stereochemistry of each amino acid and its precursors have been unambiguously assigned.     

Synthesis and absolute configuration of annuionone A

Synthesis of both enantiomers of annuionone A (1), an allelopathic agent isolated from Helianthus annuus (sunflower), was accomplished. The absolute configuration of the naturally occurring 1 was determined to be 1S,5R,8R.