Preparative resolution of (±)-trans-1,2-diaminocyclohexane by means of preferential crystallization of its citrate monohydrate

Even if (±)-trans-1,2-diaminocyclohexane crystallizes as a conglomerate, its low melting point (?10 °C) and its sensitivity to light, CO₂, O₂, and moisture make this molecule difficult to resolve. It has been shown that the citrate monohydrate of this compound crystallizes as a stable conglomerate with a high thermal stability (up to 163 °C) with no drawbacks as to those listed above for the pure diamine. The crystal structure of this salt, resolved by single crystal X-ray diffraction, reveals structural features consistent with the thermal stability of this phase. Several preferential crystallization attempts (AS3PC) have been performed at a 100 ml scale and at a one liter scale in water with and without additives. Finally a productivity of 40 g per batch per liter of solvent per hour was achieved with a crude enantiomeric purity better than 90%. A simple recrystallization of the crude crops gives quantitatively the crystalline compound with an ee >99% proving the absence of partial solid solution at room temperature.     

Efficient resolution of (±)-pantolactone by inclusion crystallization with the use of chiral 1,1,2-triphenylethane-1,2-diol

Enantioselective formation of crystalline 1 : 1 host—guest complexes with (R)-or (S)-1,1,2-triphenylethane-1,2-diol as a host compound allows efficient preparative resolution of (±)-pantolactone. Optically active pantolactones (98%ee) were obtained in 65–67% yield. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1489–1490, August, 2000.     

Enzymatic resolution of (±)-1-ferrocenylethylamine

(±)-1-Ferrocenylethylamine was resolved by a highly enantioselective acetylation catalyzed by Candida antarctica B lipase.     

Enantiomeric resolution of (±)-licarin A by high-performance liquid-chromatography using a chiral stationary phase

(±)-Licarin A (1), a neolignan obtained by the oxidative coupling reaction of isoeugenol, had in this study its enantiomers resolved. A novel, quick and efficient enantiomeric resolution of 1 was directly performed by chiral high-performance liquid chromatography (HPLC-PDA) protocol (CHIRALPACK^® AD column; 9:1 (v/v) n-hexane:2-propanol; 1.0 mL/min). This method provided a chromatogram profile with a well-resolved peak separation. After isolation of each enantiomer with ee > 99.9%, they were analysed in a polarimeter. Compound 2, which showed a retention time (t_r) of 12.13 min, was the (+)-enantiomer and compound 3 (t_r = 18.90 min) was the (−)-enantiomer.     

Enzymatic resolution of (±)-cis- and (±)-trans-1-aminoindan-2-ol and (±)-cis- and (±)-trans-2-aminoindan-1-ol

Pseudomonas cepacia lipase (PSL) efficiently catalyses the kinetic resolution of (±)-cis- and (±)-trans-1-aminoindan-2-ol through the O-acylation reaction of the corresponding N-benzyloxycarbonyl derivative using vinyl acetate as the acyl donor. In a similar way, cis-N-Cbz-2-aminoindan-1-ol is resolved when isopropenyl acetate is used as the acylating agent. The enantioselectivity of the reaction was lower for (±)-trans-N-Cbz-2-aminoindan-1-ol due to the different steric requirements for the two conformers of this substrate.     

An efficient large scale resolution of (±)-threo-methylphenidate hydrochloride (Ritalin® hydrochloride)

An efficient and large scale preparation of (2R,2′R)-(+)-threo-methylphenidate hydrochloride (3) by the resolution of (±)-threo-methylphenidate hydrochloride (1) salt with O,O′-dibenzoyl-d-(+)-tartaric acid in the presence of 4-methylmorpholine is described.     

Efficient kinetic resolution of (±)-4-methyl-Hajos–Parrish ketone by baker’s yeast reduction

Kinetic resolution of (±)-4-methyl-Hajos–Parrish ketone (±)-2a using baker’s yeast reduction was investigated. The reaction rate and enantiomeric purity depended on the concentration of substrate and yeast. Under concentrated conditions, (−)-2a and the alcohol (+)-3 were obtained in high enantiomeric excess.     

Enzymatic resolution of (±)-2-(Nβ-t-butoxycarbonyl-Nα-methylhydrazino)cycloalkanols

Racemates of cis- and trans-2-(N_β-t-butoxycarbonyl-N_α-methylhydrazino)cyclopentanols and -cyclohexanols 1–4 were resolved through lipase PS- or Novozym 435-catalysed asymmetric acylation of the secondary OH group at the (R)-stereogenic centre. High enantioselectivity (E >200) was observed when vinyl acetate or vinyl butyrate was used in diisopropyl ether, resulting in the enantiopure hydrazino esters 1a–4a and hydrazino alcohols 1b–4b. Methanolysis of the esters 1a–4a afforded the corresponding 2-hydrazinocycloalkanols 1c–4c (ee usually >95%).     

Highly substituted oxabicyclic derivatives from furan: synthesis of (±)-platensimycin

A stereocontrolled approach to a key platensimycin intermediate was achieved from a commercially available furylcarboxylate. Key to our approach is the highly efficient formal [4 + 3] cyclocondensation of a substituted furan with tetrabromocyclopropene along with an intramolecular γ-alkylation to construct the final ring of the caged intermediate.     

Preparation of (±)-α-alkylated amino acid derivatives via imidazoles

Photooxidatlon of N-methoxy-2,4-disubstituted imidazoles, readily available by way of a three component cyclization followed by O-alkylation, leads to stable acyl Imines which react with various organometallics to afford α,α-disubstituted amino acid bis-amides in good yields.     

An Expeditious Total Synthesis of (±)-Sempervirol, (±)-Sugiol and (±)-Xanthopherol Methyl Ether by Acid-Catalyzed Cyclialkylation Route

An expeditious total synthesis of (±)-sempervirol (7) (±)-sugiol (8), and (±)-xanthopherol methyl ether (9) by extension of a simple general route is described. The stereochemical results of the cyclialkylation of 2-(2-p) and (2-m-isopropylphenylethyl)-1,3,3-trimethylcyclohexanols (1e) and (1f) follow the general pattern observed earlier.     

Facile Syntheses of (±)-Curcuphenol, (±)-Curcudiol, (±)-Curcuhydroquinone,and (±)-Curcuquinone

The syntheses of (±)-curcuphenol 1, (±)-curcudiol 2, (±)-curcuhydroquinone 3, and (±)-curcuquinone 4 have been achieved. The key steps involved in the syntheses were the Reformatsky reaction and hydrogenation reaction.     

Total Synthesis of (±)-Boschnialactone and (±)-Tetrahydroanhydrodesoxyaucubigenin

A total synthesis of (±)-boschnialactone ( 1 ) and (±)-tertahydroanhydrodesoxyaucubigenin ( 2 ) is described and trisubstitued cyclopentenoid 3 is a key intermediate.     

Total synthesis of (±)-maistemonine and (±)-stemonamide

The first total synthesis of polycyclic Stemona alkaloid maistemonine has been achieved. The efficient approach features a stereoselective intramolecular Schmidt reaction, a ketone-ester condensation, and a Reformatsky reaction. Additionally, another Stemona alkaloid stemonamide was divergently synthesized from a common intermediate.     

Enzymatic resolution of (±)-conduritol-B,a key intermediate for the synthesis of glycosidase inhibitors

Lipases from porcine pancreas, Candida cylindracea and Mucor miehei (adsorbed on support, Lipozyme^® IM) catalysed in t-butylmethylether the alcoholysis of rac-conduritol-B peracetate, (±)-1, by n-butanol to give enantiopure (2S,3S)-diacetoxy-(1R,4R)-dihydroxycyclohex-5-ene, (−)-3, and (1S,2R,3R,4S)-tetraacetoxy-cyclohex-5-ene, (+)-1. The enantioforms (+)- and (−)-conduritol-B, obtained after chemical hydrolysis of (−)-3 and (+)-1, respectively, may be employed to prepare both the enantiomers of conduritol-B epoxide and cyclophellitol, powerful inhibitors of glycosidases.