Asymmetric Aza‐Morita–Baylis–Hillman‐Type Reactions: The Highly Enantioselective Reaction between Unmodified α,β‐ Unsaturated Aldehydes and N‐Acylimines by Organo‐co‐catalysis

The highly enantioselective organo‐co‐catalytic aza‐Morita–Baylis–Hillman (MBH)‐type reaction between N‐carbamate‐protected imines and α,β‐unsaturated aldehydes has been developed. The organic co‐catalytic system of proline and 1,4‐diazabicyclo[2.2.2]octane (DABCO) enables the asymmetric synthesis of the corresponding N‐Boc‐ and N‐Cbz‐protected β‐amino‐α‐alkylidene‐aldehydes in good to high yields and up to 99% ee. In the case of aza‐MBH‐type addition of enals to phenylprop‐2‐ene‐1‐imines, the co‐catalytic reaction exhibits excellent 1,2‐selectivity. The organo‐co‐catalytic aza‐MBH‐type reaction can also be performed by the direct highly enantioselective addition of α,β‐unsaturated aldehydes to bench‐stable N‐carbamate‐protected α‐amidosulfones to give the corresponding β‐amino‐α‐alkylidene‐aldehydes with up to 99% ee. The organo‐co‐catalytic aza‐MBH‐type reaction is also an expeditious entry to nearly enantiomerically pure β‐amino‐α‐alkylidene‐amino acids and β‐amino‐α‐alkylidene‐lactams (99% ee). The mechanism and stereochemistry of the chiral amine and DABCO co‐catalyzed aza‐MBH‐type reaction are also discussed.     

Highly Enantioselective Phase‐Transfer Catalytic α‐Alkylation of α‐tert‐Butoxycarbonyllactams: Construction of β‐Quaternary Chiral Pyrrolidine and Piperidine Systems

A new enantioselective α‐alkylation of α‐tert‐butoxycarbonyllactams for the construction of β‐quaternary chiral pyrrolidine and piperidine core systems is reported. α‐Alkylations of N‐methyl‐α‐tert‐butoxycarbonylbutyrolactam and N‐diphenylmethyl‐α‐tert‐butoxycarbonylvalerolactam under phase‐transfer catalytic conditions (solid potassium hydroxide, toluene, −40 °C) in the presence of (S,S)‐3,4,5‐trifluorophenyl‐3,3′,5,5′‐tetrahydro‐2,6‐bis(3,4,5‐trifluorophenyl)‐4,4′‐spirobi[4H‐dinaphth[2,1‐c:1′,2′‐e]azepinium] bromide [(S,S)‐NAS Br] (5 mol%) afforded the corresponding α‐alkyl‐α‐tert‐butoxycarbonyllactams in very high chemical (up to 99%) and optical yields (up to 98% ee). Our new catalytic systems provide attractive synthetic methods for pyrrolidine‐ and piperidine‐based alkaloids and chiral intermediates with β‐quaternary carbon centers.     

Three‐Component Staudinger‐Type Stereoselective Synthesis of C‐Glycosyl‐β‐lactams and their Use as Precursors for C‐Glycosyl Isoserines and Dipeptides. A Polymer‐Assisted Solution‐Phase Approach

A collection of 4‐(C‐galactosyl)‐ and 4‐(C‐ribosyl)‐β‐lactams featuring different substituents at C‐3 and N‐1 was prepared by combining in a one‐pot procedure a formyl C‐glycoside, a primary amine, and a substituted acetyl chloride in the presence of base (Staudinger‐type reaction). Sulfonyl chloride and aminomethylated resins were used in sequence to remove excess of components and by‐products. Two pure C‐glycosyl‐β‐lactams were effectively transformed into C‐glycosyl‐N‐Boc‐β‐amino‐α‐hydroxy esters (C‐glycosyl isoserines) and a C‐ribosyl dipeptide via base‐promoted heterocycle ring opening by methanol and L ‐phenylalanine methyl ester, respectively.     

Polyaniline doped with α, ω‐alkanedisulfonic acids: preparation and characterization

The use of α, ω‐alkanedisulfonic acid, HO₃S(CH₂)_nSO₃H (n = 1, 4, 6 and 12), as a dopant for polyaniline (PANi) was investigated. This series of disulfonic acids with varying chain lengths were synthesized and used in the doping of PANi. The doped polymers showed conductivity in the range 10^?2 to 10^?1 S cm^?1. Thermal studies showed that the doped polymers, depending on the chain length of α,ω‐alkanedisulfonic acid, were stable up to ca 300 °C and the thermal stability decreased with increasing dopant chain length. The thermal stability of α,ω‐alkanedisulfonic acid‐doped PANi was higher than that of alkanesulfonic acid‐doped PANi which typically degrades around 250 °C, suggesting a moderately broader processing window for α,ω‐alkanedisulfonic acid‐doped PANi for blending with other thermoplastics. Copyright © 2012 Society of Chemical Industry     

Synthesis of well‐defined polystyrene by radical polymerization using 1,1,2,2‐tetraphenyl‐1,2‐ethanediol/feCl3/PPh3 initiation system

Well‐defined polystyrenes with an α‐hydrogen atom and an ω‐chlorine atom end groups and narrow polydispersity (M_n = 2500–4200, M_w/M_n = 1.29–1.48) have been synthesized by a free radical polymerization process using a 1,1,2,2‐tetraphenyl‐1,2‐ethanediol (TPED)/FeCl₃/PPh₃ initiation system. The end groups were monitored by ¹H nuclear magnetic resonance spectroscopy. When the polymerization of styrenes in bulk carried out at 120°C and the ratio of [St]₀ : [TPED]₀ : [FeCl₃]₀ : [PPh₃]₀ was 200 : 1 : 4 : 12, the polymerization exhibited some living/controlled radical polymerization characteristics. The polymerization mechanism was proposed proceeding via a reverse atom transfer radical polymerization (ATRP). Because the polymers obtained were end‐functionalized by chlorine atoms, they were used as macroinitiators to proceed chain extension polymerization in the presence of CuCl/2,2′‐bipyridine catalyst system via a conventional ATRP process. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 77: 1607–1613, 2000     

Synthesis and characterization of polyrotaxanes comprising α‐cyclodextrins and poly(ε‐caprolactone) end‐capped with poly(butyl methacrylate)s

Biodegradable polyrotaxane‐based triblock copolymers were synthesized via the bulk atom transfer radical polymerization (ATRP) of n‐butyl methacrylate (BMA) initiated with polypseudo‐rotaxanes (PPRs) built from a distal 2‐bromoisobutyryl end‐capped poly(ε‐caprolactone) (Br‐PCL‐Br) with α‐cyclodextrins (α‐CDs) in the presence of Cu(I)Br/N,N,N′,N″,N″‐pentamethyldiethylenetriamine at 45 ºC. The structure was characterized in detail by means of ¹H NMR, gel permeation chromatography, wide‐angle X‐ray diffraction, DSC and TGA. When the feed molar ratio of BMA to Br‐PCL‐Br was changed from 128 to 300, the degree of polymerization of PBMA blocks attached to two ends of the PPRs was in the range 382 ? 803. Although about a tenth of the added α‐CDs were still threaded onto the PCL chain after the ATRP process, the movable α‐CDs made a marked contribution to the mechanical strength enhancement, blood anticoagulation activity and protein adsorption repellency of the resulting copolymers. Meanwhile, they could also protect the copolymers from the attack of H₂O and Lipase AK Amano molecules, exhibiting a lower mass loss as evidenced in hydrolytic and enzymatic degradation experiments. © 2013 Society of Chemical Industry     

Multi‐Enzymatic Synthesis of Optically Pure β‐Hydroxy α‐Amino Acids

A novel enzymatic production system of optically pure β‐hydroxy α‐amino acids was developed. Two enzymes were used for the system: an N‐succinyl L ‐amino acid β‐hydroxylase (SadA) belonging to the iron(II)/α‐ketoglutarate‐dependent dioxygenase superfamily and an N‐succinyl L ‐amino acid desuccinylase (LasA). The genes encoding the two enzymes are part of a gene set responsible for the biosynthesis of peptidyl compounds found in the Burkholderia ambifaria AMMD genome. SadA stereoselectively hydroxylated several N‐succinyl aliphatic L ‐amino acids and produced N‐succinyl β‐hydroxy L ‐amino acids, such as N‐succinyl‐L ‐β‐hydroxyvaline, N‐succinyl‐L ‐threonine, (2S,3R)‐N‐succinyl‐L ‐β‐hydroxyisoleucine, and N‐succinyl‐L ‐threo‐β‐hydroxyleucine. LasA catalyzed the desuccinylation of various N‐succinyl‐L ‐amino acids. Surprisingly, LasA is the first amide bond‐forming enzyme belonging to the amidohydrolase superfamily, and has succinylation activity towards the amino group of L ‐leucine. By combining SadA and LasA in a preparative scale production using N‐succinyl‐L ‐leucine as substrate, 2.3 mmol of L ‐threo‐β‐hydroxyleucine were successfully produced with 93% conversion and over 99% of diastereomeric excess. Consequently, the new production system described in this study has advantages in optical purity and reaction efficiency for application in the mass production of several β‐hydroxy α‐amino acids.

     

Synthesis of α‐Carbolines Starting from 2,3‐Dichloropyridines and Substituted Anilines

9H‐α‐Carbolines have been prepared via consecutive intermolecular Buchwald–Hartwig reaction and Pd‐catalyzed intramolecular direct arylation from commercially available 2,3‐dichloropyridines and substituted anilines. The combination of a high reaction temperature (180 °C) and the use of DBU were found to be crucial for the intramolecular direct arylation reactions of the 3‐chloro‐N‐phenylpyridin‐2‐amines as no reaction was observed at 120 °C and 180 °C using different inorganic and other organic bases. On the other hand, nitrogen‐methylated pyridine analogues of these substrates {N‐[3‐chloro‐1‐methylpyridin‐2(1H)‐ylidene]anilines} do undergo ring closure at 120 °C, with K₃PO₄ as base, affording the respective 1‐methyl‐1H‐α‐carbolines in good yields.     

Chemoenzymatic Preparation of Enantiopure Homoadamantyl β‐Amino Acid and β‐Lactam Derivatives

Racemic cis‐10‐azatetracyclo[7.2.0.1^2,6.1^4,8]tridecan‐11‐one was prepared from homoadamant‐4‐ene by chlorosulfonyl isocyanate addition. The transformation of the β‐lactam to the corresponding β‐amino ester followed by Candida antarctica lipase A‐catalyzed enantioselective (E>>200) N‐acylation with 2,2,2‐trifluoroethyl butanoate afforded methyl (1R,4R,5S,8S)‐5‐aminotricyclo[4.3.1.1^3,8]undecane‐4‐carboxylate and the (1S,4S,5R,8R)‐butanamide with>99% ee at 50% conversion. Alternatively, transformation of the β‐lactam to the corresponding N‐hydroxymethyl‐β‐lactam and the following Pseudomonas cepacia (currently Burkholderia cepacia) lipase‐catalyzed enantioseletive O‐acylation provided the (1S,4S,6R,9R)‐alcohol (ee=87%) and the corresponding (1R,4R,6S,9S)‐butanoate (ee>99%). In the latter method, competition for the enzyme between the (1R,4R,6S,9S)‐butanoate, 2,2,2‐trifluoroethyl butanoate and the hydrolysis product, butanoic acid, tended to stop the reaction at about 45% conversion and finally gave racemization in the (1S,4S,6R,9R)‐alcohol with time.     

(R)‐α‐Lipoyl‐Glycyl‐L‐Prolyl‐L‐Glutamyl Dimethyl Ester Codrug as a Multifunctional Agent with Potential Neuroprotective Activities

The (R)‐α‐lipoyl‐glycyl‐L ‐prolyl‐L ‐glutamyl dimethyl ester codrug (LA‐GPE, 1 ) was synthesized as a new multifunctional drug candidate with antioxidant and neuroprotective properties for the treatment of neurodegenerative diseases. Physicochemical properties, chemical and enzymatic stabilities were evaluated, along with the capacity of LA‐GPE to penetrate the blood–brain barrier (BBB) according to an in vitro parallel artificial membrane permeability assay for the BBB. We also investigated the potential effectiveness of LA‐GPE against the cytotoxicity induced by 6‐hydroxydopamine (6‐OHDA) and H₂O₂ on the human neuroblastoma cell line SH‐SY5Y by using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) reduction assay. Our results show that codrug 1 is stable at both pH 1.3 and 7.4, exhibits good lipophilicity (log P=1.51) and a pH‐dependent permeability profile. Furthermore, LA‐GPE was demonstrated to be significantly neuroprotective and to act as an antioxidant against H₂O₂‐ and 6‐OHDA‐induced neurotoxicity in SH‐SY5Y cells.     

Enhancing Thermostability and Organic Solvent Tolerance of ω‐Transaminase through Global Incorporation of Fluorotyrosine

Here, we have utilized the incorporation of non‐canonical amino acids as a tool kit to improve enzyme properties for organic synthesis applications. The global incorporation of 3‐fluorotyrosine (FY) into ω‐transaminase (ω‐TA) to give ω‐TA[FY] enhanced the thermostability and organic solvent tolerance without altering substrate specificity and enantioselectivity. Moreover, ω‐TA[FY] was able to completely convert 25 mM of acetophenone into (S)‐1‐phenylethylamine (ee>99%) in the presence of 20% DMSO (v/v) which is ∼2‐fold higher when compared to wild‐type ω‐TA.

     

Synthesis and characterization of polyimide‐γ‐Fe2O3 nanocomposites

Novel polyimide‐γ‐Fe₂O₃ hybrid nanocomposite films (PI/γ‐Fe₂O₃) has been developed from the poly(amic acid) salt of oxydianiline with different weight percentages (5, 10, 15 wt %) of γ‐Fe₂O₃ using tetrahydrofuran (THF) and N,N‐dimethylacetamide (DMAc) as aprotic solvents. The prepared polyimide‐γ‐Fe₂O₃ nanocomposite films were characterized for their structure, morphology, and thermal behavior employing Fourier transform infrared spectroscopy (FTIR), scanning electron micrograph (SEM), transmission electron micrograph (TEM), X‐ray diffraction (XRD), ¹³C‐NMR, and thermal analysis (TGA/DSC) techniques. These studies showed the homogenous dispersion of γ‐Fe₂O₃ in the polyimide matrix with an increase in the thermal stability of the composite films on γ‐Fe₂O₃ loadings. Magnetization measurements (magnetic hysteresis traces) have shown very high values of coercive force indicating their possible use in memory devices and in other related applications. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 834–840, 2007     

Structural Determinants for the Non‐Canonical Substrate Specificity of the ω‐Transaminase from Paracoccus denitrificans

Substrate binding pockets of ω‐transaminase (ω‐TA) consist of a large (L) pocket capable of dual recognition of hydrophobic and carboxyl substituents, and a small (S) pocket displaying a strict steric constraint that permits entry of a substituent no larger than an ethyl group. Despite the unique catalytic utility of ω‐TA enabling asymmetric reductive amination of carbonyl compounds, the severe size exclusion occurring in the S pocket has limited synthetic applications of ω‐TA to access structurally diverse chiral amines and amino acids. Here we report the first example of an ω‐TA whose S pocket shows a non‐canonical steric constraint and readily accommodates up to an n‐butyl substituent. The relaxed substrate specificity of the (S)‐selective ω‐TA, cloned from Paracoccus denitrificans (PDTA), afforded efficient asymmetric syntheses of unnatural amino acids carrying long alkyl side chains such as L ‐norvaline and L ‐norleucine. Molecular modeling using the recently released X‐ray structure of PDTA could pinpoint an exact location of the S pocket which had remained dubious. Entry of a hydrophobic substituent in the L pocket was found to have the S pocket accept up to an ethyl substituent, reminiscent of the canonical steric constraint. In contrast, binding of a carboxyl group to the L pocket induced a slight movement of V153 away from the small‐pocket‐forming residues. The resulting structural change elicited excavation of the S pocket, leading to formation of a narrow tunnel‐like structure allowing accommodation of linear alkyl groups of carboxylate‐bearing substrates. To verify the active site model, we introduced site‐directed mutagenesis to six active site residues and examined whether the point mutations alleviated the steric constraint in the S pocket. Consistent with the molecular modeling results, the V153A variant assumed an elongated S pocket and accepted even an n‐hexyl substituent. Our findings provide precise structural information on substrate binding to the active site of ω‐TA, which is expected to benefit rational redesign of substrate specificity of ω‐TA.

     

Bio‐Based Hybrid Magnetic Latex Particles Containing Encapsulated γ ‐Fe2O3 by Miniemulsion Copolymerization of Soybean Oil‐Acrylated Methyl Ester and Styrene

This work reports the use of acrylated fatty acid methyl ester (AFAME) as a biomonomer for the synthesis of bio‐based hybrid magnetic particles poly(styrene‐co‐AFAME)/γ‐Fe₂O₃ produced by miniemulsion polymerization. Poly(styrene‐co‐AFAME)/γ‐Fe₂O₃ can be tailored for use in various fields by varying the content of AFAME. The strategy employed is to encapsulate superparamagnetic iron oxide nanoparticles (SPIONs) as γ‐Fe₂O₃ into a styrene/AFAME‐based copolymer matrix. Raman spectroscopy is employed to ensure the formation of the SPIONs (γ‐Fe₂O₃) obtained by a co‐precipitation technique followed by oxidation of Fe₃O₄. The functionalization of SPIONs with oleic acid (OA) is carried out to increase the SPIONs–monomer affinity. The presence of OA on the surface of γ‐Fe₂O₃ is certified by identification of main absorption bands by fourier‐transform infrared spectroscopy (FTIR). Thermal analysis (differential thermogravimetry/differential thermo analysis and differential scanning calorimetry) results of poly(styrene‐co‐AFAME)/γ‐Fe₂O₃ show an increase in AFAME content leading to a lower copolymer glass transition temperature (T _g). Dynamic light scattering (DLS) measurements result in poly(styrene‐co‐AFAME)/γ‐Fe₂O₃ particles with diameter in the range of 100–150 nm. It is also observed by transmission electron microscopy (TEM) and cryo‐TEM techniques that γ‐Fe₂O₃ particles are successfully encapsulated into the poly(styrene‐co‐AFAME) matrix.     

Polymerization of 4‐(4′‐N‐1,8‐naphthalimidophenyl)‐1,2,4‐triazolidine‐3,5‐dione with diisocyanates

4‐(4′‐Aminophenyl)‐1,2,4‐triazolidine‐3,5‐dione ( 1 ) was reacted with 1,8‐naphthalic anhydride ( 2 ) in a mixture of acetic acid and pyridine (3 : 2) under refluxing temperature and gave 4‐(4′‐N‐1,8‐naphthalimidophenyl)‐1,2,4‐triazolidine‐3,5‐dione ( NIPTD ) ( 3 ) in high yield and purity. The compound NIPTD was reacted with excess n‐propylisocyanate in N,N‐dimethylacetamide solution and gave 1‐(n‐propylamidocarbonyl)‐4‐[4′‐(1,8‐naphthalimidophenyl)]‐1,2,4‐triazolidine‐3,5‐dione ( 4 ) and 1,2‐bis(n‐propylamidocarbonyl)‐4‐[4′‐(1,8‐naphthalimidophenyl)]‐1,2,4‐ triazolidine‐3,5‐dione ( 5 ) as model compounds. Solution polycondensation reactions of monomer 3 with hexamethylene diisocyanate ( HMDI ), isophorone diisocyanate ( IPDI ), and tolylene‐2,4‐diisocyanate ( TDI ) were performed under microwave irradiation and conventional solution polymerization techniques in different solvents and in the presence of different catalysts, which led to the formation of novel aliphatic‐aromatic polyureas. The polycondensation proceeded rapidly, compared with conventional solution polycondensation, and was almost completed within 8 min. These novel polyureas have inherent viscosities in a range of 0.06–0.20 dL g^?1 in conc. H₂SO₄ or DMF at 25°C. Some structural characterization and physical properties of these novel polymers are reported. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 2861–2869, 2003     

Rapid living free‐radical polymerization of methyl acrylate under 60Co γ‐ray irradiation at room temperature

Rapid living free‐radical polymerization of methyl acrylate under ⁶⁰Co γ‐ray irradiation in the presence of benzyl 1H‐imidazole‐1‐carbodithioate at room temperature is reported. The results showed that the polymerization is a fast living process, and that the molecular weight of the polymer is as high as 39 600 g mol^?1 at 68 % conversion with M_w/M_n = 1.09 within 68 min. The polymerization rate was markedly influenced by the structures of thiocarbonylthio compounds. Copyright © 2004 Society of Chemical Industry     

DVD substrate application for polycarbonate end‐capped with 4‐α‐cumylphenol

Using 4‐α‐cumylphenol as the end‐capping agent, polycarbonates (PCs) with a viscosity‐average molecular weight (M_v) of 13,800 were prepared. DVD substrates were molded using these PCs. DVD substrates using PCs end‐capped with 4‐α‐cumylphenol (CP–PCs) have lower retardation than do those using conventional PCs end‐capped with 4‐tert‐butylphenol (TBP–PCs). Using CP–PC, it is possible to bring the mold temperature down about 20°C from the standard conditions of molding DVD substrates using TBP–PC at the same radial birefringence. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 404–406, 2003     

Eu2+‐doped strontium aluminum silicon nitrides having α‐SiAlON and polytypoid structures

Yellow single crystals of aluminum silicon nitrides containing strontium and europium were prepared by heating starting mixtures of Sr₃N₂, Si₃N₄, AlN, and EuN at 2050°C and 0.85 MPa of N₂ for 8 hours. Single‐crystal X‐ray diffraction revealed that prismatic crystals 20‐100 μm in size were Sr_0.31Al_0.62Si_11.38N₁₆:Eu (trigonal, a=7.7937(2) Å, c=5.6519(2) Å, space group P31c), which are isotypic with Sr‐α‐SiAlON, Sr_m/2Al_m+nSi_12?m?nN_16?nO_n, with m=0.62 and n=0. The Eu²⁺ content was approximately 1 at.% of Sr contained in the framework of corner‐sharing (Al/Si)N₄ tetrahedra with an occupancy of 0.154(2). Block‐shaped crystals with a side length of 50‐300 μm were a new polytypoid of Sr‐α‐SiAlON, Sr_2.97Eu_0.03Al₆Si₂₄N₄₀. Streak lines were observed in the direction of the c* axis in the X‐ray oscillation photographs, indicating stacking faults of the structure. The fundamental X‐ray reflections were indexed with a hexagonal cell (a=7.9489(3) Å, c=14.3941(6) Å). The structure was analyzed with a model of space group P in which one of the six Al/Si sites was statistically split into two sites with occupancies of 0.673(5) and 0.227(5). The atomic arrangements in the layers of the structure were similar to those of Sr‐α‐SiAlON, but the stacking sequences of the layers were different. The peak wavelengths and full widths at half maximum of emission spectra measured for the single crystals of Sr_0.31Al_0.62Si_11.38N₁₆:Eu and Sr_2.97Eu_0.03Al₆Si₂₄N₄₀ were 583 nm and 87 nm, and 584 nm and 91 nm, respectively, under 400 nm wavelength light excitation at room temperature.     

Homogeneous graft copolymerization of chitosan with butyl acrylate by γ‐irradiation via a 6‐O‐maleoyl‐N‐phthaloyl‐chitosan intermediate

The graft copolymerization of butyl acrylate (BA) onto chitosan was tried via a new protection‐graft‐deprotection procedure. About 6‐O‐maleoyl‐N‐phthaloyl‐chitosan was synthesized and characterized by Fourier transform infrared spectra analysis (FT‐IR) and ¹H‐NMR. Because the intermediate 6‐O‐maleoyl‐N‐phthaloyl‐chitosan was soluble in organic solvents, the graft copolymerization was carried out in a homogeneous system. Grafting was initiated by γ‐irradiation. The graft extent was dependent on the irradiation dose and the concentration of BA monomer, and copolymers with grafting above 100% were readily prepared. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 489–493, 2006     

Organocatalytic Asymmetric Mannich Reactions of 5H‐Oxazol‐4‐ones: Highly Enantio‐ and Diastereoselective Synthesis of Chiral α‐Alkylisoserine Derivatives

The first organocatalytic Mannich reaction of 5H‐oxazol‐4‐ones with various readily prepared aryl‐ and alkylsulfonimides has been developed. Two commercially available pseudoenantiomeric Cinchona alkaloids‐derived tertiary amine/ureas have been demonstrated as the most efficient catalysts to access the opposite enantiomers of the Mannich products with equally excellent enantio‐ and diastereoselectivities. From the Mannich adducts, important α‐methyl‐α‐hydroxy‐β‐amino acid derivatives, such as the α‐methylated C‐13 side chain of taxol and taxotere, can be conveniently prepared.