Practical Synthesis of (S)‐(+)‐3‐Octanol by Lipase‐Catalyzed Enantioselective Acetylation

(S)‐(+)‐3‐Octanol (S)‐1 was prepared in high enantiomeric excess through catalyzed acetylation of racemic alcohol 1 by using lipase from Candida antarctica (Chirazyme L‐2) in the presence of vinyl acetate in toluene at 30°C. The pure (S)‐1 was obtained in 73% isolated yield with 62% conversion. Moreover, acetate (R)‐2 was converted to (S)‐1 via mesylation and followed by hydrolysis using sodium bicarbonate solution in 44% yield.     

Enantioselective synthesis of β-amino-diacids

An efficient route to orthogonally protected β-amino-diacids is described: chiral derivative 3 was shown to be a precursor of enantiopure substituted β-amino acids. The key step of the procedure is a diastereoselective reduction of β-enaminolactones 5 by NaBH₃CN in CH₂Cl₂. A study concerning the regio- and diastereoselectivity of alkylation of β-enaminolactone 3 is also presented.     

First Enantioselective Synthesis of Daphneticin

An enantioselective total synthesis of chiral daphneticin is reported firstly.     

Chiral (S)‐(+) 1‐Substituted Aryl‐4‐(1‐phenyl) Ethylformamido‐5‐amino‐1,2,3‐triazole: A New Class of Chiral Ligands for the Silver(I)‐Promoted Enantioselective Allylation of Aldehydes

Some novel chiral ligands, (S)‐(+) 1‐substituted aryl‐4‐(1‐phenyl) ethylformamido‐5‐amino‐1,2,3‐triazoles, were prepared starting from 1‐substituted aryl‐4‐ethoxycarbonyl‐5‐amino‐1,2,3‐triazoles and other reagents. They were used as catalytic chiral ligands in the silver (I)‐promoted enantioselective allylation reaction of aldehydes with allyltributyltin.     

Enantioselective,Potentiometric Membrane Electrodes Based on Cyclodextrins for the Assay of L‐ and D‐2‐Hydroxyglutaric Acid

Abstract

Enantioselective, potentiometric membrane electrodes (EPMEs) based on immobilization of β‐, γ‐cyclodextrin (CD) or 2‐hydroxy‐3‐trimethylammoniopropyl‐β‐cyclodextrin (as chloride salt) (β‐CD‐derivative) in carbon paste have been designed. The β‐CD and β‐CD‐derivative‐based electrodes were applied in the 10^?8–10^?6 and 10^?7–10^?5 mol/L concentration ranges for the determination of L‐2‐hydroxyglutaric acid (L‐2‐HGA), whereas γ‐CD‐based electrode was applied for the determination of D‐2‐hydroxyglutaric acid (D‐2‐HGA) in the concentration range 10^?6–10^?4 mol/L. The β‐CD‐based EPME showed the lowest detection limit (1×10^?9 mol/L). The enantioselectivity and selectivity of the proposed electrodes for the assay of L‐2‐HGA and D‐2‐HGA, respectively, were determined over D‐2‐HGA/L‐2‐HGA, creatine, and creatinine. The proposed EPMEs can be applied for the enantioanalysis of 2‐hydroxyglutaric acid in urine samples.     

Enantioselective total synthesis of amphidinolide f

A common-intermediate approach is utilized in the total synthesis of amphidinolide?F to access both the C1-C8 and the C18-C25 portions of the macrolide. A silver-catalyzed rearrangement/cyclization was employed to construct the two tetrahydrofuran rings. A Felkin-controlled, dienyl lithium addition to an α-chiral aldehyde incorporated both the C9-C11 diene and the alcohol at C8. An umpolung sulfone alkylation/oxidative desulfurization sequence is employed to couple the two moieties.     

Enantioselective synthesis of functionalized γ-butyrolactones

Sharpless asymmetric dihydroxylation and aminohydroxylation of (E)-dimethyl-2-alkylidene glutarates 2 were shown to afford enantio-enriched or enantiopure highly functionalized γ-butyrolactones 3 and 7.     

Enantioselective Synthesis of (R)‐2‐Methylalkanoic Acids: A Convenient Approach to α‐Substituted Chiral Carboxylic Acid Derivatives

Abstract

Racemization‐free deacylation of N‐acylimidazolidine‐2‐ones using lithium hydroperoxide affords the corresponding α‐substituted chiral carboxylic acids in high yield while permitting recovery of the chiral auxiliary.     

An Efficient Synthesis of Derivatives of 2‐Acetamido‐4‐amino‐2,4,6‐trideoxy‐D‐galactopyranose

Abstract

Methyl 2‐acetamido‐4‐amino‐2,4,6‐trideoxy‐α‐D‐galactopyranoside (10) was synthesized from D‐glucosamine hydrochloride in eight steps in an overall yield of 31%. Key steps include the selective benzoylation at O‐3 of methyl 2‐acetamido‐2,6‐dideoxy‐α‐D‐glucopyranoside in 89% yield and the subsequent Mitsunobu reaction using diphenylphosphoryl azide as the azide source which proceeded in 92% yield. Di‐ and mono‐benzyloxycarbonyl derivatives of 10 were also prepared.     

Preparation of Some Derivatives of N‐tert‐Butyldecahydro‐3‐isoquinoline Carboxamide

N‐tert‐Butyldecahydro‐3‐isoquinoline carboxamide (1) is a key structural fragment present in a variety of medicinally important HIV protease inhibitors. Derivatives of this carboxamide were prepared by alkylation with either 2‐iodoethanol, allyl bromide, or bromoacetaldehyde dimethylacetal. The corresponding aldehyde of the dimethylacetal derivative was prepared by reaction with BBr₃ in CH₂Cl₂.     

Determination of L‐Vesamicol in Serum Samples Using Enantioselective,Potentiometric Membrane Electrodes Based on Antibiotics

Abstract

Enantioselective, potentiometric membrane electrodes (EPMEs) based on antibiotics are proposed for the enantioanalysis of L‐vesamicol. A carbon paste was modified with antibiotics (vancomycin, teicoplanin, and teicoplanin modified with acetonitrile), as chiral selectors. The EPMEs based on antibiotics were reliably used for enantiopurity tests of L‐vesamicol using the direct potentiometric technique. The following linear concentration ranges: 1.0×10^?6–1.0×10^?4, 1.0×10^?6–1×10^?3 and 1×10^?7?1×10^?2 mol/L; and detection limits: 1.1×10^?7, 9.6×10^?8, and 3.6×10^?8 mol/L were determine for vancomycin, teicoplanin, and teicoplanin modified with acetonitrile–based EPMEs, respectively. The proposed EPMEs were applied for the enantioanalysis of L‐vesamicol in urine samples.     

Preparation of Alkyl Carbamate of 1‐Protected Indole‐3‐methylamine as a Precursor of Indole‐3‐methylamine

A series of alkyl carbamates 3 of 1‐protected indole‐3‐methylamines, alkyl carbamates 6 of thiophenylmethylamines, and pyrrolylmethylamines were prepared from the corresponding acetamides 2 and 5 in good to excellent yields via diacetoxyiodobenzene‐promoted Hofmann rearrangement. For a successful Hofmann rearrangement, an electron‐withdrawing group on position 1 of indolylacetamide and pyrrolylacetamide was required. The alkyl carbamate 3g was demonstrated to serve well as a stable precursor of 1‐protected indole‐3‐methylamine 1.     

Enantioselective organocatalytic α-fluorination of cyclic ketones

The first highly enantioselective α-fluorination of ketones using organocatalysis has been accomplished. The long-standing problem of enantioselective ketone α-fluorination via enamine activation has been overcome via high-throughput evaluation of a new library of amine catalysts. The optimal system, a primary amine functionalized Cinchona alkaloid, allows the direct and asymmetric α-fluorination of a variety of carbo- and heterocyclic substrates. Furthermore, this protocol also provides diastereo-, regio-, and chemoselective catalyst control in fluorinations involving complex carbonyl systems.     

Enantioselective synthesis of (−)-γ-jasmolactone

The title compound was prepared in seven steps starting from the commercially available 4-ketopimelic acid. The key step features an enantioselective lactonization promoted by PPL.     

Enantioselective Synthesis and Racemization of (−)-Sinoracutine

Sinoracutine is a recently isolated alkaloid with unusual stereochemical and biological properties. It features an unprecedented tetracyclic 6/6/5/5 skeleton that bears an N-methylpyrrolidine ring fused to a cyclopentenone. Interestingly, both enantiomers of sinoracutine have been independently isolated from the same plant, yet the molecule does not appear to occur as a racemate. Here, we present a short synthesis of (−)-sinoracutine that relies on a highly diastereoselective Pauson–Khand reaction and a Mandai–Claisen reaction to install the quaternary stereocenter. Our work establishes the absolute configuration of the levorotatory isomer and suggests that the optical purity of sinoracutine varies in nature due to its gradual racemization. Experimental evidence supports this proposal, and a plausible mechanism for the racemization is provided.     

One‐Pot Synthesis of Ene‐Lactams via N‐Debenzylation of Keto‐Containing N‐2,4‐Dimethoxylbenzylamides

Abstract

A general method of ene‐lactam preparation is described. Ene‐lactams can be prepared efficiently from keto‐containing N‐2,4‐dimethoxylbenzylamides in good to excellent yields. This method is applicable for the preparation of substituted δ‐, γ‐, and ?‐ene‐lactams and bicyclic ene‐lactams.     

Synthesis of 2,3‐Dihydroxy‐1‐Epilupinine

The 1,3‐dipolar cycloaddition of unsaturated D‐threo‐hexaldonolactone 3 and a six‐membered cyclic nitrone 11 led to a single adduct 15, which could be transformed into (1S, 2S, 3S, 9aS)‐2,3‐dihydroxy‐1‐hydroxymethyl‐quinolizidine 28 related to epilupinine via a reaction sequence involving rearrangement of the six‐membered lactone ring into a five‐membered one, removal of the terminal carbon atom from the sugar chain, cleavage of the N‐O bond, and the intramolecular alkylation of the nitrogen atom.      

Enantioselective Total Synthesis of (−)-Cephalotanin B

Cephalotaxus diterpenoids are attractive natural products with intriguing molecular frameworks and promising biological features. As a structurally unusual member, (−)-cephalotanin B possesses an extraordinarily congested heptacyclic skeleton, three lactone units, and nine consecutive stereocenters. Herein, we report an enantioselective total synthesis of (−)-cephalotanin B based on a divergent asymmetric Michael addition reaction, a novel Pauson–Khand/deacyloxylation process discovered in the development of a second-generation stereoselective Pauson–Khand reaction protocol, and an epoxide-opening/elimination/dual-lactonization cascade to construct the challenging propeller-shaped A–B–C ring system as key transformations.     

Bromination of 4‐Dichloromethyl‐4‐methylcyclohexa‐2,5‐dien‐1‐ones

Bromination of 4‐dichloromethyl‐4‐methylcyclohexa‐2,5‐dien‐1‐one and 4‐dichloromethyl‐3,4‐dimethylcyclohexa‐2,5‐dien‐1‐one has been studied. The reaction conditions required for the formation of mono‐, di‐, and tribrominated products have been optimized.