Induced Folding of Protein‐Sized Foldameric β‐Sandwich Models with Core β‐Amino Acid Residues

The mimicry of protein‐sized β‐sheet structures with unnatural peptidic sequences (foldamers) is a considerable challenge. In this work, the de novo designed betabellin‐14 β‐sheet has been used as a template, and α→β residue mutations were carried out in the hydrophobic core (positions 12 and 19). β‐Residues with diverse structural properties were utilized: Homologous β³‐amino acids, (1R,2S)‐2‐aminocyclopentanecarboxylic acid (ACPC), (1R,2S)‐2‐aminocyclohexanecarboxylic acid (ACHC), (1R,2S)‐2‐aminocyclohex‐3‐enecarboxylic acid (ACEC), and (1S,2S,3R,5S)‐2‐amino‐6,6‐dimethylbicyclo[3.1.1]heptane‐3‐carboxylic acid (ABHC). Six α/β‐peptidic chains were constructed in both monomeric and disulfide‐linked dimeric forms. Structural studies based on circular dichroism spectroscopy, the analysis of NMR chemical shifts, and molecular dynamics simulations revealed that dimerization induced β‐sheet formation in the 64‐residue foldameric systems. Core replacement with (1R,2S)‐ACHC was found to be unique among the β‐amino acid building blocks studied because it was simultaneously able to maintain the interstrand hydrogen‐bonding network and to fit sterically into the hydrophobic interior of the β‐sandwich. The novel β‐sandwich model containing 25 % unnatural building blocks afforded protein‐like thermal denaturation behavior.     

Identification of (6R)‐5,6,7,8‐Tetrahydro‐D‐monapterin (=(6R)‐2‐Amino‐5,6,7,8‐tetrahydro‐6‐[(1R,2R)‐1,2,3 ‐trihydroxypropyl]pteridin‐4(3H)‐one) as the Native Pteridine in Tetrahymena pyriformis

The structure of the native pteridine in Tetrahymena pyriformis was determined as (6R)‐5,6,7,8‐tetrahydro‐D ‐monapterin (=(6R)‐2‐amino‐5,6,7,8‐tetrahydro‐6‐[(1R,2R)‐1,2,3‐trihydroxypropyl]pteridin‐4(3H)‐one; 4 ). First, the configuration of the 1,2,3‐trihydroxypropyl side chain was confirmed as D ‐threo by the fluorescence‐detected circular dichroism (FDCD) spectrum of its aromatic pterin derivative 2 obtained by I₂ oxidation (Fig. 1). The configuration at the 6‐position of 4 was determined as (R) by comparison of its hexaacetyl derivative 6 with authentic (6R)‐ and (6S)‐hexaacetyl‐5,6,7,8‐tetrahydro‐D ‐monapterins 6 and 7 , respectively, in the HPLC, LC/MS, and LC‐MS/MS (Figs. 3 – 6). (6R)‐5,6,7,8‐Tetrahydro‐D ‐monapterin ( 4 ) is a newly discovered natural tetrahydropterin.     

Metabolism of Deuterated Isomeric 6,7‐Dihydroxydodecanoic Acids in Saccharomyces cerevisiae – Diastereo‐ and Enantioselective Formation and Characterization of 5‐Hydroxydecano‐4‐lactone (=4,5‐Dihydro‐5‐(1‐hydroxyhexyl)furan‐2(3H)‐one) Isomers

The chemical synthesis of deuterated isomeric 6,7‐dihydroxydodecanoic acid methyl esters 1 and the subsequent metabolism of esters 1 and the corresponding acids 1a in liquid cultures of the yeast Saccharomyces cerevisiae was investigated. Incubation experiments with (6R,7R)‐ or (6S,7S)‐6,7‐dihydroxy(6,7‐²H₂)dodecanoic acid methyl ester ((6R,7R)‐ or (6S,7S)‐(6,7‐²H₂)‐ 1 , resp.) and (±)‐threo‐ or (±)‐erythro‐6,7‐dihydroxy(6,7‐²H₂)dodecanoic acid ((±)‐threo‐ or (±)‐erythro‐(6,7‐²H₂)‐ 1a , resp.) elucidated their metabolic pathway in yeast (Tables 1–3). The main products were isomeric ²H‐labeled 5‐hydroxydecano‐4‐lactones 2 . The absolute configuration of the four isomeric lactones 2 was assigned by chemical synthesis via Sharpless asymmetric dihydroxylation and chiral gas chromatography (Lipodex ^® E). The enantiomers of threo‐ 2 were separated without derivatization on Lipodex ^® E; in contrast, the enantiomers of erythro‐ 2 could be separated only after transformation to their 5‐O‐(trifluoroacetyl) derivatives. Biotransformation of the methyl ester (6R,7R)‐(6,7‐²H₂)‐ 1 led to (4R,5R)‐ and (4S,5R)‐(2,5‐²H₂)‐ 2 (ratio ca. 4 : 1; Table 2). Estimation of the label content and position of (4S,5R)‐(2,5‐²H₂)‐ 2 showed 95% label at C(5), 68% label at C(2), and no ²H at C(4) (Table 2). Therefore, oxidation and subsequent reduction with inversion at C(4) of 4,5‐dihydroxydecanoic acid and transfer of ²H from C(4) to C(2) is postulated. The 5‐hydroxydecano‐4‐lactones 2 are of biochemical importance: during the fermentation of Streptomyces griseus, (4S,5R)‐ 2 , known as L‐factor, occurs temporarily before the antibiotic production, and (?)‐muricatacin (=(4R,5R)‐5‐hydroxy‐heptadecano‐4‐lactone), a homologue of (4R,5R)‐ 2 , is an anticancer agent.     

Two 17‐hydroxy‐9(10→5)‐abeo‐estr‐4‐ene‐3,10‐diones

(5S,9S,17S)‐17‐Hydroxy‐9(10→5)‐abeo‐estr‐4‐ene‐3,10‐dione, C₁₈H₂₆O₃, (II), and (5R,9R,17S)‐17‐hydroxy‐9(10→5)‐abeo‐estr‐4‐ene‐3,10‐dione, C₁₈H₂₆O₃, (III), are equimolecular products of the Fe^II‐induced transposition of 10β‐hydro­peroxy‐17β‐hydroxyestr‐4‐en‐3‐one, (I). With respect to reagent mol­ecules, the configuration at C9 is retained for (II) while it is inverted in (III). The conformations of the five‐ and six‐membered rings are compared.     

Enantioselective Synthesis of β‐Amino Acids,Part 13

Inexpensive acryloyl chloride was converted in 91% overall yield to two derivatives of β‐alanine, (R,R,R)‐ 6 and (R,R,S)‐ 6 , containing two chiral auxiliaries. C‐Alkylation of (R,R,R)‐ and (R,R,S)‐ 6 via a dianion derivative, was performed by direct metallation with 2.2 equiv. of lithium hexamethyldisilazane (LHMDS) in THF at ?78°. C‐Alkylation of (R,R,S)‐ 6 ‐Li₂ (‘matched' pair of chiral auxiliaries) afforded the mono‐alkylated products 8 – 11 in 29–96% yield and 54–95% stereoselectivity. Employment of LiCl as an additive generally increased stereoselectivities, whereas the effect of HMPA as a cosolvent was erratic. Chemical correlation of the major diastereoisomer from the alkylation reactions with (S)‐α‐alkyl‐β‐alanine ( 12 – 15 ) showed that addition of the electrophile preferentially takes place on the enolate's Si‐face. This conclusion is also supported by molecular‐modeling studies (ab initio HF/3‐21G), which indicate that the lowest‐energy conformation for (R,R,S)‐ 6 ‐Li₂ presents the more sterically hindered Re‐face of the enolate. The theoretical studies also predict a determining role for N? Li? O chelation in (R,R,S)‐ 6 ‐Li₂, giving rise to an interesting ‘ion‐triplet' configuration for the dilithium dianion.     

Metabolism of Deuterated threo‐Dihydroxy Fatty Acids in Saccharomyces cerevisiae: Enantioselective Formation and Characterization of Hydroxylactones and γ‐Lactones

Biotransformation of (±)‐threo‐7,8‐dihydroxy(7,8‐²H₂)tetradecanoic acids (threo‐(7,8‐²H₂)‐ 3 ) in Saccharomyces cerevisiae afforded 5,6‐dihydroxy(5,6‐²H₂)dodecanoic acids (threo‐(5,6‐²H₂)‐ 4 ), which were converted to (5S,6S)‐6‐hydroxy(5,6‐²H₂)dodecano‐5‐lactone ((5S,6S)‐(5,6‐²H₂)‐ 7 ) with 80% e.e. and (5S,6S)‐5‐hydroxy(5,6‐²H₂)dodecano‐6‐lactone ((5S,6S)‐5,6‐²H₂)‐ 8 ). Further β‐oxidation of threo‐(5,6‐²H₂)‐ 4 yielded 3,4‐dihydroxy(3,4‐²H₂)decanoic acids (threo‐(3,4‐²H₂)‐ 5 ), which were converted to (3R,4R)‐3‐hydroxy(3,4‐²H₂)decano‐4‐lactone ((3R,4R)‐ 9 ) with 44% e.e. and converted to ²H‐labeled decano‐4‐lactones ((4R)‐(3‐²H₁)‐ and (4R)‐(2,3‐²H₂)‐ 6 ) with 96% e.e. These results were confirmed by experiments in which (±)‐threo‐3,4‐dihydroxy(3,4‐²H₂)decanoic acids (threo‐(3,4‐²H₂)‐ 5 ) were incubated with yeast. From incubations of methyl (5S,6S)‐ and (5R,6R)‐5,6‐dihydroxy(5,6‐²H₂)dodecanoates ((5S,6S)‐ and (5R,6R)‐(5,6‐²H₂)‐ 4a ), the (5S,6S)‐enantiomer was identified as the precursor of (4R)‐(3‐²H₁)‐ and (2,3‐²H₂)‐ 6 ). Therefore, (4R)‐ 6 is synthesized from (3S,4S)‐ 5 by an oxidation/keto acid reduction pathway involving hydrogen transfer from C(4) to C(2). In an analogous experiment, methyl (9S,10S)‐9,10‐dihydroxyoctadecanoate ((9S,10S)‐ 10a ) was metabolized to (3S,4S)‐3,4‐dihydroxydodecanoic acid ((3S,4S)‐ 15 ) and converted to (4R)‐dodecano‐4‐lactone ((4R)‐ 18 ).     

α‐Propargyl amino acid‐derived optically active novel substituted polyacetylenes: Synthesis,secondary structures,and responsiveness to ions

Novel optically active substituted acetylenes HC? CCH₂CR¹(CO₂CH₃)NHR² [(S)‐/(R)‐ 1 : R¹ = H, R² = Boc, (S)‐ 2 : R¹ = CH₃, R² = Boc, (S)‐ 3 : R¹ = H, R² = Fmoc, (S)‐ 4 : R¹ = CH₃, R² = Fmoc (Boc = tert‐butoxycarbonyl, Fmoc = 9‐fluorenylmethoxycarbonyl)] were synthesized from α‐propargylglycine and α‐propargylalanine, and polymerized with a rhodium catalyst to provide the polymers with number‐average molecular weights of 2400–38,900 in good yields. Polarimetric, circular dichroism (CD), and UV–vis spectroscopic analyses indicated that poly[(S)‐ 1 ], poly[(R)‐ 1 ], and poly[(S)‐ 4 ] formed predominantly one‐handed helical structures both in polar and nonpolar solvents. Poly[(S)‐ 1a ] carrying unprotected carboxy groups was obtained by alkaline hydrolysis of poly[(S)‐ 1 ], and poly[(S)‐ 4b ] carrying unprotected amino groups was obtained by removal of Fmoc groups of poly[(S)‐ 4 ] using piperidine. Poly[(S)‐ 1a ] and poly[(S)‐ 4b ] also exhibited clear CD signals, which were different from those of the precursors, poly[(S)‐ 1 ] and poly[(S)‐ 4 ]. The solution‐state IR measurement revealed the presence of intramolecular hydrogen bonding between the carbamate groups of poly[(S)‐ 1 ] and poly[(S)‐ 1a ]. The plus CD signal of poly[(S)‐ 1a ] turned into minus one on addition of alkali hydroxides and tetrabutylammonium fluoride, accompanying the red‐shift of λ_max. The degree of λ_max shift became large as the size of cation of the additive. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Confirmation of the Absolute (3R,3′S,6′R)‐Configuration of (all‐E)‐3′‐Epilutein

Circular dichroism (CD) spectroscopy was used to distinguish between the isomeric (all‐E)‐configured 3′‐epilutein ( 2 ) and 6′‐epilutein ( 8 ) to establish the absolute configuration of epilutein samples of different (natural and semisynthetic) origin, including samples of 2 obtained from thermally processed sorrel. Thus, the CD data of lutein ( 1 ) and epilutein samples ( 2 ) were compared. Our results unambiguously confirmed the (3R,3′S,6′R)‐configuration of all epilutein samples. Compound 2 was thoroughly characterized, and its ¹³C‐NMR data are published herewith for the first time.     

Synthesis of the Spermidine Alkaloids (−)‐(2R,3R)‐ and (−)‐(2R,3S)‐3‐Hydroxycelacinnine: Macrocyclization with Oxirane‐Ring Opening and Inversion via Cyclic Sulfamidates

The two epimers (?)‐ 1a and (?)‐ 1b of the macrocyclic lactam alkaloid 3‐hydroxycelacinnine with the (2R,3R) and (2R,3S) absolute configurations, respectively, were synthesized by an alternative route involving macrocyclization with the regio‐ and stereoselective oxirane‐ring opening by the terminal amino group (Schemes 2 and 6). Properly N‐protected chiral trans‐oxirane precursors provided (2R,3R)‐macrocycles after a one‐pot deprotection‐macrocyclization step under moderate dilution (0.005–0.01M ). The best yields (65–85%) were achieved with trifluoroacetyl protection. Macrocyclization of the corresponding cis‐oxiranes was unsuccessful for steric reasons. Inversion at OH? C(3) via nucleophilic displacement of the cyclic sulfamidate derivative with NaNO₂ led to (2R,3S)‐macrocycles. The synthesized (?)‐(2R,3S)‐3‐hydroxycelacinnine ((?)‐ 1b ) was identical to the natural alkaloid.     

Chiral Heterospirocyclic 2H‐Azirin‐3‐amines as Synthons for 3‐Amino‐2,3,4,5‐tetrahydrofuran‐3‐carboxylic Acid and Their Use in Peptide Synthesis

The heterospirocyclic N‐methyl‐N‐phenyl‐5‐oxa‐1‐azaspiro[2.4]hept‐1‐e n‐2‐amine (6 ) and N‐(5‐oxa‐1‐azaspiro[2.4]hept‐1‐en‐2‐yl)‐(S)‐proline methyl ester ( 7 ) were synthesized from the corresponding heterocyclic thiocarboxamides 12 and 10 , respectively, by consecutive treatment with COCl₂, 1,4‐diazabicyclo[2.2.2]octane, and NaN₃ (Schemes 1 and 2). The reaction of these 2H‐azirin‐3‐amines with thiobenzoic and benzoic acid gave the racemic benzamides 13 and 14 , and the diastereoisomeric mixtures of the N‐benzoyl dipeptides 15 and 16 , respectively (Scheme 3). The latter were separated chromatographically. The configurations and solid‐state conformations of all six benzamides were determined by X‐ray crystallography. With the aim of examining the use of the new synthons in peptide synthesis, the reactions of 7 with Z‐Leu‐Aib‐OH to yield a tetrapeptide 17 (Scheme 4), and of 6 with Z‐Ala‐OH to give a dipeptide 18 (Scheme 5) were performed. The resulting diastereoisomers were separated by means of MPLC or HPLC. NMR Studies of the solvent dependence of the chemical shifts of the NH resonances indicate the presence of an intramolecular H‐bond in 17 . The dipeptides (S,R)‐ 18 and (S,S)‐ 18 were deprotected at the N‐terminus and were converted to the crystalline derivatives (S,R)‐ 19 and (S,S)‐ 19 , respectively, by reaction with 4‐bromobenzoyl chloride (Scheme 5). Selective hydrolysis of (S,R)‐ 18 and (S,S)‐ 18 gave the dipeptide acids (R,S)‐ 20 and (S,S)‐ 20 , respectively. Coupling of a diastereoisomeric mixture of 20 with H‐Phe‐O^tBu led to the tripeptides 21 (Scheme 5). X‐Ray crystal‐structure determinations of (S,R)‐ 19 and (S,S)‐ 19 allowed the determination of the absolute configurations of all diastereoisomers isolated in this series.     

Stereoselective Reduction of `Capsanthol‐3′‐ones' (=3,6′‐Dihydroxy‐β,κ‐caroten‐3′‐ones) by Complex Hydrides

The (3R,5′R,6′R)‐ and (3R,5′R,6′S)‐capsanthol‐3′‐one (=3,6′‐dihydroxy‐β,κ‐caroten‐3′‐one; 4 and 5 , resp.) were reduced by different complex metal hydrides containing organic ligands. The ratio of the thus obtained diastereoisomeric (3′S)‐capsanthols 2 and 3 or (3′R)‐capsanthols 6 and 7 , respectively, was investigated. Four complex hydrides showed remarkable stereoselectivity and produced the (3′R,6′S)‐capsanthol ( 6 ) in 80 – 100% (see Table 1). The starting materials and the products were characterized by UV/VIS, CD, ¹H‐ and ¹³C‐NMR, and mass spectra.     

Enzyme‐Catalyzed Stereoselective Synthesis of Two Novel Carbasugar Derivatives

Enzymatic resolution of racemic 1,4,5,6‐tetrachloro‐2‐(hydroxymethyl)‐7,7‐dimethoxybicyclo[2.2.1]hept‐5‐ene (rac‐ 1 ) using various lipases in vinyl acetate as acetyl source was studied. The obtained enantiomerically enriched (+)‐(1,4,5,6‐tetrachloro‐7,7‐dimethoxybicyclo[2.2.1]hept‐5‐en‐2‐yl)methyl acetate ((+)‐ 2 ; 94% ee), upon treatment with Na in liquid NH₃, followed by Amberlyst‐15 resin in acetone, provided (−)‐5‐(hydroxymethyl)bicyclo[2.2.1]hept‐2‐en‐7‐one ((−)‐ 7 ), which is a valuable precursor for the synthesis of carbasugar derivatives. Subsequent Baeyer–Villiger oxidation afforded a nonseparable mixture of bicyclic lactones, which was subjected to LiAlH₄ reduction and then acetylation. The resultant compounds (−)‐ 11 and (+)‐ 12 were submitted to a cis‐hydroxylation reaction, followed by acetylation, to afford the novel carbasugar derivatives (1S,2R,3S,4S,5S)‐4,5‐bis(acetoxymethyl)cyclohexane‐1,2,3‐triyl triacetate ((−)‐( 13 )) and (1R,3R,4R,6R)‐4,6‐bis(acetoxymethyl)cyclohexane‐1,2,3‐triyl triacetate ((−)‐( 14 )), respectively, with pseudo‐C₂‐symmetric configuration. The absolute configuration of enantiomerically enriched unreacted alcohol (−)‐ 1 (68% ee) was determined by X‐ray single‐crystal analysis by anchoring optically pure (R)‐1‐phenylethanamine. Based on the configurational correlation between (−)‐ 1 and (+)‐ 2 , the absolute configuration of (+)‐ 2 was determined as (1R,2R,4S).     

The Absolute Configuration of (+)‐Ethyl cis‐1‐Benzyl‐3‐hydroxypiperidine‐4‐carboxylate and (+)‐4‐Ethyl 1‐Methyl cis‐3‐Hydroxypiperidine‐1,4‐dicarboxylate; a Revision

Discrepancies between chiroptical data from the literature and our determination of the structure of the title compounds (+)‐ 5 and (+)‐ 9a were resolved by an unambiguous assignment of their absolute configuration. Accordingly, the dextrorotatory cis‐3‐hydroxy esters have (3R,4R)‐ and the laevorotatory enantiomers (3S,4S)‐configuration. The final evidences were demonstrated on both enantiomers (+)‐ and (?)‐ 5 by biological reduction of 4 by bakers' yeast and stereoselective [Ru^II(binap)]‐catalyzed hydrogenations of 4 (Scheme 2), by the application of the NMR Mosher method on (+)‐ and (?)‐ 5 (Scheme 3), as well as by the transformation of (+)‐ 5 into a common derivative and chiroptical correlation (Scheme 4).     

Synthesis and Absolute Configuration at C(8) of ‘p‐Menthane‐3,8,9‐triol’ Derived from (–)‐Isopulegol

Two diastereoisomers of the new, potentially insecticidal ‘p‐menthane‐3,8,9‐triol’ (=(2S)‐ and (2R)‐ 2‐[(1R,2R,4R)‐2‐hydroxy‐4‐methylcyclohexyl]propane‐1,2‐diol; (8S)‐ and (8R)‐ 1 ), have been synthesized from (–)‐isopulegol by both conventional dihydroxylation and catalytic Sharpless dihydroxylation (Scheme). The absolute configuration at C(8) of the corresponding orthoformate adduct (8S)‐ 3a was determined by ¹H‐NMR and X‐ray crystallographic analysis (Figure).     

Reaction of Elemol with Acetic Acid/Perchloric Acid: Characterization of a Novel Oxide and (+)‐β‐Cyperone

The minor unidentified compounds of the acetic acid/perchloric acid dehydration of elemol ( 1 ) were fully characterized. The structure and relative configuration of the less polar fragrant compound 2 , named elemoxide, was deduced by 1D‐ and 2D‐NMR data including C,C‐connectivity, NOE, and NOESY experiments. The absolute configuration was established as (3S,3aR,7aR)‐1,3,3a,4,7,7a‐hexahydro‐6‐isopropyl‐1,1,3,3a‐tetramethylisobenzofuran ( 2 ) on the basis of its preparation from elemol ( 1 ). (+)‐β‐cyperone ( 3 ), a known sesquiterpene, was also identified as a minor product of the reaction. A plausible mechanistic explanation for the formation of elemoxide ( 2 ) and (+)‐β‐cyperone ( 3 ) is presented.     

Precursor‐Directed Biosynthesis: Stereospecificity for Branched‐Chain Diketides of the β‐Ketoacyl‐ACP Synthase Domain 2 of 6‐Deoxyerythronolide B Synthase

Modular polyketide synthases such as 6‐deoxyerythronolide B synthase (DEBS) catalyze the biosynthesis of structurally complex natural products. Streptomyces coelicolor CH999/pJRJ2 harbors a plasmid encoding DEBS(KS1⁰), a mutant form of 6‐deoxyerythronolide B synthase that is blocked in the formation of 6‐deoxyerythronolide B ( 1 , 6‐dEB) due to a mutation in the active site of the ketosynthase (KS1) domain that normally catalyzes the first polyketide chain‐elongation step of 6‐dEB biosynthesis. Administration of (2S,3R,4S)‐ and (2S,3R,4R)‐3‐hydroxy‐2,4‐dimethylhexanoic acid N‐acetylcysteamine (SNAC) thioesters (= S‐[2‐(acetylamino)ethyl] (2S,3R,4S)‐ and (2S,3R,4R)‐3‐hydroxy‐2,4‐dimethylhexanethioates) 3 and 4 in separate experiments to cultures of Streptomyces coelicolor CH999/pJRJ2 led to production of the corresponding (14S)‐ and (14R)‐14‐methyl analogues of 6‐dEB, 10 and 11 , respectively. Unexpectedly, when a 3 : 2 mixture of 4 and 3 was fed under the same conditions, exclusively branched‐chain macrolactone 11 was isolated. In similar experiments, feeding of 3 and 4 to S. coelicolor CH999/pCK16, an engineered strain harboring DEBS1+TE(KS1⁰), resulted in formation of the branched‐chain triketide lactones 13 and 14 , while feeding of the 3 : 2 mixture of 4 and 3 gave exclusively 14 . The biochemical basis for this stereochemical discrimination was established by using purified DEBS module 2+TE to determine the steady‐state kinetic parameters for 3 and 4 , with the k_cat/K_M for 4 shown to be sevenfold greater than that of 3 .     

Diastereoselective Electrophilic Amination of Chiral 1‐Benzoyl‐2,3,5,6‐tetrahydro‐3‐methyl‐2‐(1‐methylethyl)pyrimidin‐4(1H)‐one for the Asymmetric Syntheses of α‐Substituted α,β‐Diaminopropanoic Acids

The chiral compounds (R)‐ and (S)‐1‐benzoyl‐2,3,5,6‐tetrahydro‐3‐methyl‐2‐(1‐methylethyl)pyrimidin‐4(1H)‐one ((R)‐ and (S)‐ 1 ), derived from (R)‐ and (S)‐asparagine, respectively, were used as convenient starting materials for the preparation of the enantiomerically pure α‐alkylated (alkyl=Me, Et, Bn) α,β‐diamino acids (R)‐ and (S)‐ 11 – 13 . The chiral lithium enolates of (R)‐ and (S)‐ 1 were first alkylated, and the resulting diasteroisomeric products 5 – 7 were aminated with ‘di(tert‐butyl) azodicarboxylate’ (DBAD), giving rise to the diastereoisomerically pure (≥98%) compounds 8 – 10 . The target compounds (R)‐ and (S)‐ 11 – 13 could then be obtained in good yields and high purities by a hydrolysis/hydrogenolysis/hydrolysis sequence.     

A Case Study on the Resolution of the 1‐i‐Butyl‐3‐methyl‐3‐phospholene 1‐Oxide via Diastereomeric Complex Formation Using TADDOL Derivatives and via Diastereomeric Coordination Complexes Formed from the Calcium Salts of O,O′‐Diaroyl‐(2R,3R)‐tartaric Acids

The resolution of 1‐i‐butyl‐3‐methyl‐3‐phospholene 1‐oxide was studied applying TADDOL [(−)‐(4R,5R)‐4,5‐bis(diphenylhydroxymethyl)‐2,2‐dimethyldioxolane], spiro‐TADDOL [(−)‐(2R,3R)‐α,α,α′,α′‐tetraphenyl‐1,4‐dioxaspiro[4.5]decan‐2,3‐dimethanol], or the acidic and neutral Ca²⁺ salts of (−)‐O,O′‐dibenzoyl‐ and (−)‐O,O′‐di‐p‐toluoyl‐(2R,3R)‐tartaric acid as the resolving agent. The absolute configuration of the P‐asymmetric center was determined by circular dichroism spectroscopy and related quantum chemical calculations. In one instance, the single crystal of the diastereomeric complex incorporating i‐butyl‐3‐phospholene oxide and spiro‐TADDOL was subjected to X‐ray analysis, which suggested a feasible hypothesis for the efficiency of the resolution process under discussion that may be an example for the “solvent‐inhibited” resolution.     

Asymmetric anionic polymerization of N‐1‐naphthylmaleimide with chiral ligand‐organometal complexes in toluene

Asymmetric anionic homopolymerizations of N‐1‐naphthylmaleimide (1‐NMI) were performed with chiral ligand/organometal complexes to form optically active polymers. Poly(1‐NMI)s obtained with methylene‐bridged bisoxazoline derivatives (Rbox)‐diethylzinc (Et₂Zn) complexes showed high specific optical rotations ([α]) from +152.3 to +191.4°. Circular dichroism spectra of the polymers exhibited a split Cotton effect in the UV absorption‐band region. According to the exciton chirality method, the absolute configuration of the polymer main chain was determined according to the following method: (+)‐poly[N‐substituted maleimides (RMI)] main chains can contain more (S,S)‐ than (R,R)‐configurations. (?)‐Poly(RMI) main chains can contain more (R,R)‐ than (S,S)‐configurations. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3556–3565, 2001     

Elucidation of the absolute configuration of rhizopine by chiral supercritical fluid chromatography and vibrational circular dichroism

The absolute configuration of rhizopine, an opine‐like natural product present in nitrogen‐fixing nodules of alfalfa infected by rhizobia, is elucidated using a combination of state‐of‐the‐art analytical and semi‐preparative supercritical fluid chromatography and vibrational circular dichroism spectroscopy. A synthetic peracetylated racemate was fractionated into its enantiomers and subjected to absolute configuration analysis revealing that natural rhizopine exists as a single enantiomer. The stereochemistry of non‐derivatized natural rhizopine corresponds to (1R,2S,3R,4R,5S,6R)‐4‐amino‐6‐methoxycyclohexane‐1,2,3,5‐tetraol.