Direct resolution of (+/-)-ephedrine and atropine into their enantiomers by impregnated TLC

Direct resolution of (+/-)-ephedrine and atropine into their enantiomers was achieved by normal-phase thin layer chromatography on silica gel plates impregnated with optically pure L-tartaric acid and L-histidine, respectively, as chiral selectors. The mobile phases enabling successful resolution were different combinations of acetonitrile-methanol-water. The spots were detected with iodine vapours and the detection limits were 2 and 6 microg, respectively, in terms of the racemate. The effects of concentration of the impregnating reagent, temperature and pH on resolution have been studied.     

Direct enantiomeric resolution of (+/-)-atenolol, (+/-)-metoprolol,and (+/-)-propranolol by impregnated TLC using L-aspartic acid as chiral selector

Resolution of three commonly used beta-blockers, (+/-)-atenolol, (+/-)-metoprolol and (+/-)-propranolol, into their enantiomers has been achieved using normal-phase TLC on silica gel plates impregnated with L-aspartic acid as the chiral selector. Different combinations of acetonitrile-methanol-water as mobile phase were found to be successful in resolving the enantiomers. The spots were detected with iodine and the detection limits were found to be 0.26 microg for atenolol and 0.23 microg for each of metoprolol and propranolol as racemate.     

Fluorescence spectroscopy of jet-cooled chiral (+/-)-indan-1-ol and its cluster with (+/-)-methyl- and ethyl-lactate

The laser-induced fluorescence excitation, dispersed fluorescence, and IR-UV double resonance spectra of chiral (+/-)-indan-1-ol have been measured in a supersonic expansion. Three low energy conformers of the molecule have been identified, and the ground state vibrational modes of each conformer are tentatively assigned with the aid of quantum chemistry calculations. The frequencies of the nu(OH) and nu(CH) stretch modes of the two most abundant conformers have been measured by fluorescence dip IR spectroscopy and have been used for their assignment. The dispersed fluorescence spectra clearly indicate the coupling of low-frequency modes, as was seen in other substituted indanes such as 1-aminoindan and 1-amino-2-indanol. (R)- and (S)-indan-1-ol distinctly form different types of clusters with (R)- and (S)- methyl- and ethyl-lactate. Both hetero- and homochiral clusters are characterized by complex spectra which exhibit a progression built on low-frequency intermolecular modes.     

A simple method of synthesis of (+/-)-2,3-diarylpiperazines and a novel method of resolution of (+/-)-2,3-diphenylpiperazine

Intramolecular reductive coupling of diimines in the presence of Zn/Ti(O(i)Pr)2Cl2 gives the corresponding (+/-)-2,3-diarylpiperazines in 73-83% yields with dl/meso ratio >99%:<1%. The (+/-)-2,3-diphenylpiperazine obtained in this way was readily resolved partially using L-(+)-tartaric acid, and the enantiomeric purity was enhanced to >99% ee via preparation of hydrogen-bonded salt aggregates using oxalic acid.     

Use of Conjugated Dienones in Cyclialkylations: The Total Syntheses of (+/-)-Barbatusol, (+/-)-Pisiferin, (+/-)-Deoxofaveline, (+/-)-Xochitlolone, and (+/-)-Faveline

Concise syntheses of five tricyclic diterpenoids are reported. The key reaction in each synthesis is a cyclialkylation of a functionalized arene with a Lewis acid-activated conjugated dienone to generate a 6,7,6-fused tricycle.     

Improved synthesis of (+/-)-4,12-dihydroxy[2.2]paracyclophane and its enantiomeric resolution by enzymatic methods: planar chiral (R)- and (S)-phanol

(+/-)-4,12-Dihydroxy[2.2]paracyclophane [(+/-)-PHANOL] is readily prepared from [2.2]paracyclophane by an improved synthetic protocol. Enzymatic kinetic resolution of its bis-acetate proceeds with good enantioselection. Separation, hydrolysis, and recrystallization provides both enantiomers of PHANOL in high enantiopurity.     

A formal total synthesis of the sesterterpenoid (+/-)-dysidiolide and approaches to the syntheses of (+/-)-6-epi-, (+/-)-15-epi-, and (+/-)-6,15-bisepidysidiolide

A formal total synthesis of the sesterterpenoid (+/-)-dysidiolide (1), a structurally novel sponge metabolite that inhibits the cdc25A protein phosphatase, and approaches to the syntheses of (+/-)-15-epi- (34), (+/-)-6-epi- (36), and (+/-)-6, 15-bisepidysidiolide (39) are described.     

Kinetic resolution and parallel kinetic resolution of methyl (+/-)-5-alkyl-cyclopentene-1-carboxylates for the asymmetric synthesis of 5-alkyl-cispentacin derivatives

Conjugate addition of lithium dibenzylamide to methyl 5-isopropyl, 5-phenyl- and 5-tert-butyl-cyclopentene-1-carboxylates occurs with high levels of substrate control (>88% de), with preferential addition to the face of the cyclic alpha,beta-unsaturated acceptor anti- to the stereodirecting 5-alkyl substituent. Treatment of a range of methyl (+/-)-5-alkyl-cyclopentene-1-carboxylates with both lithium (+/-)-N-benzyl-N-alpha-methylbenzylamide and lithium (+/-)-N-3,4-dimethoxybenzyl-N-alpha-methylbenzylamide indicates significant enantiorecognition in their mutual kinetic resolutions, with preferential addition anti- to the 5-alkyl substituent, giving the 1,2-syn-1,5-anti-arrangement (E >16) after enolate protonation anti- to the amino functionality. The kinetic resolution of a range of methyl (+/-)-5-alkyl-cyclopentene-1-carboxylates with lithium (S)-N-benzyl-N-alpha-methylbenzylamide, and their efficient parallel kinetic resolution with a pseudoenantiomeric mixture of lithium (S)-N-benzyl-N-alpha-methylbenzylamide and lithium (R)-N-3,4-dimethoxybenzyl-N-alpha-methylbenzylamide are also demonstrated, giving a range of 5-alkyl-cispentacin derivatives in >98% de and high ee after N-deprotection.     

Direct enantiomeric TLC resolution of dl-penicillamine using (R)-mandelic acid and l-tartaric acid as chiral impregnating reagents and as chiral mobile phase additive

DL-Penicillamine has been resolved into its enantiomers by normal-phase TLC using L-tartaric acid as chiral impregnating reagent as well as chiral mobile phase additive, while (R)-mandelic acid has been found to be successful as a chiral impregnating reagent. The solvent system acetonitrile-methanol-water (5:1:1, v/v) was found to be successful when L-tartaric acid was used as impregnating agent while the solvent combination acetonitrile-methanol-(0.5% l-tartaric acid in water, pH 5)-glacial acetic acid (7:1:1.1:0.7, v/v) was successful as mobile phase as it contained L-tartaric acid as the chiral additive. (R)-mandelic acid was successful as chiral impregnating reagent with ethyl acetate-methanol-water (3:1:1, v/v), as the mobile phase. The effects of concentration of chiral selectors, temperature and pH were examined on enantiomeric resolution. The spots were detected with iodine vapors and the detection limits were found to be 0.12 microg for each enantiomer of penicillamine with L-tartaric acid, under both the conditions, and 0.11 microg with (R)-mandelic acid.     

Synthesis of (+/-)-5-epi-citreoviral and (+/-)-citreoviral and the kinetic resolution of an allylic silane by a [3 + 2] annulation

[reaction: see text] The [3 + 2] annulation reaction of allylsilane 1 with an alpha-keto ester provided the highly substituted tetrahydrofuran 2 as a single diastereomer in high yield. The synthesis of (+/-)-5-epi-citreoviral and (+/-)-citreoviral has been accomplished with this annulation reaction as the key step. Using the pantolactone-derived alpha-keto ester, the allylsilane 1 has been resolved with high enantiomeric purity.     

Recent advances of optically active helical polymers as adsorbents and chiral stationary phases for chiral resolution

Chiral resolution is very important and still a big challenge due to different biological activity and same physicochemical property of one pair (R)- and (S)-isomer. There is no doubt that chiral selectors are essentially needed for chiral resolution, which can stereoselectively interact with a pair of isomers. To date, a large amount of optically active helical polymers as chiral selectors have been synthesized via two strategies. First, the target helical polymers are derived from natural polysaccharide such as cellulose and amylose. Second, they can be synthesized by polymerization of chiral monomers. Alternatively, an achiral polymer is prepared first followed by static or dynamic chiral induction. Furthermore, a part of them is harnessed as chiral stationary phases for chromatographic chiral separation and as chiral adsorbents for enantioselective adsorption/crystallization, resulting in good enantioseparation efficiency. In summary, the present review will focus on recent progress of the polymers with optical activity for chiral resolution, especially the literature published in the past 10 years. In addition, development prospects and future challenges of optically active helical polymers will be discussed in detail.     

General and efficient strategy for erythrinan and homoerythrinan alkaloids: syntheses of (+/-)-3-demethoxyerythratidinone and (+/-)-erysotramidine

[reaction: see text] A general and efficient strategy to both aromatic-type and nonaromatic-type erythrinan and homoerythrinan alkaloids has been developed. This approach involves a key two-step sequence, an alkylation of a ketone with various N-substituted iodoacetamides followed by a N-acyliminium ion promoted intramolecular cyclization, and represents one of the shortest routes to erythrinan and homoerythrinan alkaloids. As the application, the formal total synthesis of (+/-)-3-demethoxyerythratidinone and the total synthesis of (+/-)-erysotramidine have been achieved, respectively.     

General route to 4a-methylhydrofluorene diterpenoids: total syntheses of (+/-)-taiwaniaquinones d and h, (+/-)-taiwaniaquinol B, (+/-)-dichroanal B, and (+/-)-dichroanone

A general and convergent route for the synthesis of the 4a-methylhydrofluorene diterpenoids has been established through a common hexahydrofluorenone intermediate (10) obtained via Pd(0)-catalyzed reductive cyclization of a substituted 2-(2-bromobenzyl) methylene cyclohexane (13). The strategy has been successfully utilized for the synthesis of (+/-)-taiwaniaquinones D (3) and H (5), (+/-)-taiwaniaquinol B (1), (+/-)-dichroanal B (7), and (+/-)-dichroanone (8).     

C-H insertion approach to the synthesis of endo,exo-furofuranones: synthesis of (+/-)-asarinin, (+/-)-epimagnolin A, and (+/-)-fargesin

A series of novel 5-aryl-4-aryloxymethyl-3-diazotetrahydrofuran-2-ones (12, 24, and 35a/b) have been prepared and found to undergo regio- and stereoselective C-H insertion reactions to afford 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane-8-ones (18, 26, and 36a/b) with endo,exo stereochemistry. Subsequent reduction of the lactone ring and cyclization of the resulting diols 27 and 37a/b permitted the synthesis of three endo,exo-furofuran lignans: asarinin (2), fargesin (3), and epimagnolin A (4). En route to the key diazo compounds 24 and 35a/b, a modified procedure for the Ghosez keteniminium-olefin cyclization was developed, which was required to minimize the decomposition of acid-sensitive functional groups such as electron-rich benzylic ethers that were present in the target compounds 2-4.     

Stereocontrolled synthesis of polyfunctionalized cis-decalins from 2-methoxyphenols: total syntheses of (+/-)-eremopetasidione, (+/-)-3 beta-angeloyloxyfuranoeremophilane, and (+/-)-3 beta-methacryloyloxyfuranoeremophilane

A four-step stereocontrolled synthesis of polyfunctionalized cis-decalins is described, involving oxidation of 2-methoxyphenol, intermolecular Diels-Alder reaction, olefination, and Cope rearrangement. Application of this efficient strategy to the total syntheses of (+/-)-eremopetasidione, (+/-)-3 beta-angeloyloxyfuranoeremophilane, and (+/-)-3 beta-methacryloyloxyfuranoeremophilane was accomplished from creosol and ethyl vinyl ketone via a common intermediate 21.