Synthesis of 6‐amino acid substituted 4,6,7,12‐tetrahydro‐4‐oxoindolo[2,3‐a]quinolizines

In the presence of Na₂CO₃ (1S,3S)‐ and (1R,3S)‐1‐(2,2‐dimethoxyethyl)‐2‐(1,3‐dioxobutyl)‐3‐(1,3‐dioxo‐butyl)oxymethyl‐1,2,3,4‐tetrahydrocarboline ( 1 ) were transformed into (1S,3S)‐ and (1R,3S)‐1‐(2,2‐dimethoxyethyl)‐2‐(1,3‐dioxobutyl)‐3‐hydroxymethyl‐1,2,3,4‐tetrahydrocarboline ( 2 ), which were cyclized to (6S)‐3‐acetyl‐6‐hydroxymethyl‐4,6,7,12‐tetrahydro‐4‐oxoindolo[2,3‐a]quinolizine ( 4 ), via(6S,12bS)‐ and (6S,12bR)‐3‐acetyl‐2‐hydroxyl‐6‐hydroxymethyl‐1,2,3,4,6,7,12,12b‐octahydro‐4‐oxoindolo[2,3‐a]quinoline ( 3 ). (6S)‐ 4 was coupled with Boc‐Gly, Boc‐L‐Asp(β‐benzyl ester), or Boc‐L‐Gln to give 6‐amino acid substituted (6S)‐3‐acetyl‐4,6,7,12‐tetrahydro‐4‐oxoindolo[2,3‐a]quinolizines 5a , 5b , or 5c , respectively. After the removal of Boc from (6S)‐ 5a (6S)‐3‐acetyl‐6‐glycyl‐4,6,7,12‐tetrahydro‐4‐oxoindolo[2,3‐a]quinolizine ( 6 ) was obtained. The anticancer activities of (6S)‐ 5 and (6S)‐ 6 in vitro were tested.     

Optically Active 4‐Substituted (S)‐2‐Phenyl‐2‐oxazolines

(R)‐4‐Hydroxymethyl‐2‐phenyl‐2‐oxazoline (R)‐ 1 ) was prepared from (L)‐serine. The respective tosylate ((S)‐ 2 ) was converted into sulfides (S)‐ 4 and (S)‐ 5 , and sulfone (S)‐ 6 , useful starting materials for the elaboration of additional chiral centers. A previously reported [ α]_D ²⁵ value for (R)‐ 4 is corrected.     

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.     

Synthesis of poly(1‐hexene)s end‐functionalized with phenols

Electrophilic alkylations of phenol/2,6‐dimethylphenol were performed with vinylidene‐terminated poly(1‐hexene)s using BF₃·OEt₂ catalyst. Vinylidene‐terminated poly(1‐hexene)s with M_n varying from 400 to 10000 were prepared by bulk polymerization of 1‐hexene at 50 to ?20 °C using Cp₂ZrCl₂/MAO catalysts. The phenol/2,6‐dimethylphenol‐terminated poly(1‐hexene)s was characterized by NMR (¹H, ¹³C), UV, IR and vapor phase osmometer (VPO). The isomer distribution (ortho, para and ortho/para) was determined by ¹³P NMR using a phosphitylating reagent, namely 2‐chloro‐1,3,2‐dioxaphospholane. The number‐average degree of functionality (F_n) >0.9 with >95% para selectivity could be achieved using low‐molecular‐weight oligomers of poly(1‐hexene)s. Copyright © 2005 Society of Chemical Industry     

Gold(I)‐Catalyzed Tandem Alkoxylation/Lactonization of γ‐Hydroxy‐α,β‐Acetylenic Esters

The formation of 4‐alkoxy‐2(5H)‐furanones was achieved via tandem alkoxylation/lactonization of γ‐hydroxy‐α,β‐acetylenic esters catalyzed by 2 mol% of [2,6‐bis(diisopropylphenyl)imidazol‐2‐ylidine]gold bis(trifluoromethanesulfonyl)imidate [Au(IPr)(NTf₂)]. The economic and simple procedure was applied to a series of various secondary propargylic alcohols allowing for yields of desired product of up to 95%. In addition, tertiary propargylic alcohols bearing mostly cyclic substituents were converted into the corresponding spiro derivatives. Both primary and secondary alcohols reacted with propargylic alcohols at moderate temperatures (65–80 °C) in either neat reactions or using 1,2‐dichloroethane as a reaction medium allowing for yields of 23–95%. In contrast to [Au(IPr)(NTf₂)], reactions with cationic complexes such as [2,6‐bis(diisopropylphenyl)imidazol‐2‐ylidine](acetonitrile)gold tetrafluoroborate [Au(IPr)(CH₃CN)][BF₄] or (μ‐hydroxy)bis{[2,6‐bis(diisopropylphenyl)imidazol‐2‐ylidine]gold} tetrafluoroborate or bis(trifluoromethanesulfonyl)imidate – [{Au(IPr)}₂(μ‐OH)][X] (X=BF₄, NTf₂) – mostly stop after the alkoxylation. Analysis of the intermediate proved the exclusive formation of the E‐isomer which allows for the subsequent lactonization.     

Synthesis and Highly Stereoselective Hydrogenation of the Statin Precursor Ethyl (5S)‐5,6‐Isopropylidenedioxy‐3‐oxohexanoate

A search for the large‐scale preparation of (5S)‐5,6‐(isopropylidenedioxy)‐3‐oxohexanoates ( 2 ) – a key intermediate in the synthesis of pharmacologially important statins – starting from (S)‐malic acid is described. The synthesis of the required initial compound methyl (3S)‐3,4‐(isopropylidenedioxy)butanoate ( 1 ) by Moriwake’s reduction of dimethyl (S)‐malate ( 3 ) has been improved. Direct 2‐C chain elongation of ester 1 using the lithium enolate of tert‐butyl acetate has been shown to be successful at a 3‐ to 5‐fold excess of the enolate. Unfortunately, the product, tert‐butyl (5S)‐5,6‐(isopropylidenedioxy)‐3‐oxohexanoate ( 2a ) is unstable during distillation. Ethyl (5S)‐5,6‐(isopropylidenedioxy)‐3‐oxohexanoate ( 2b ) was prepared alternatively on a multigram scale from (3S)‐3,4‐(isopropylidenedioxy)butanoic acid ( 7 ) by activation with N,N′‐carbonyldiimidazole and subsequent reaction with Mg(OOCCH₂COOEt)₂. A convenient pathway for the in situ preparation of the latter is also described. Ethyl ester ( 2b ) can be advantageously purified by distillation. The stereochemistry of the catalytic hydrogenation of β‐keto ester ( 2b ) to ethyl (5S)‐5,6‐(isopropylidenedioxy)‐3‐hydrohyhexanoate (syn‐ 6 and anti‐ 6 ) has been studied using a number of homogeneous achiral and chiral Rh(I) and Ru(II) complexes with phosphine ligands. A comparison of Rh(I) and Ru(II) catalysts with (S)‐ and (R)‐BINAP as chiral ligands revealed opposite activity in dependence on the polarity of the solvent. No influence of the chiral backbone of substrate 2b on the enantioselectivity was noted. A ratio of syn‐ 6 /anti‐ 6 =2.3 was observed with an achiral (Ph₃P)₃RuCl₂ catalyst. Ru[(R)‐Tol‐BINAP]Cl₂ neutralized with one equivalent of AcONa afforded the most efficient catalytic system for the production of optically pure syn‐(5S)‐5,6‐isopropylidenedioxy‐3‐hydroxyhexanoate (syn‐ 6 ) at a preparative substrate/catalyst ratio of 1000:1.     

α‐Keto Phenylamides as P1′‐Extended Proteasome Inhibitors

The major challenge for proteasome inhibitor design lies in achieving high selectivity for, and activity against, the target, which requires specific interactions with the active site. Novel ligands aim to overcome off‐target‐related side effects such as peripheral neuropathy, which is frequently observed in cancer patients treated with the FDA‐approved proteasome inhibitors bortezomib ( 1 ) or carfilzomib ( 2 ). A systematic comparison of electrophilic headgroups recently identified the class of α‐keto amides as promising for next generation drug development. On the basis of crystallographic knowledge, we were able to develop a structure–activity relationship (SAR)‐based approach for rational ligand design using an electronic parameter (Hammett’s σ) and in silico molecular modeling. This resulted in the tripeptidic α‐keto phenylamide BSc4999 [(S)‐3‐(benzyloxycarbonyl‐(S)‐leucyl‐(S)‐leucylamino)‐5‐methyl‐2‐oxo‐N‐(2,4‐dimethylphenyl)hexanamide, 6 a ], a highly potent (IC₅₀=38 nM ), cell‐permeable, and slowly reversible covalent inhibitor which targets both the primed and non‐primed sites of the proteasome’s substrate binding channel as a special criterion for selectivity. The improved inhibition potency and selectivity of this new α‐keto phenylamide makes it a promising candidate for targeting a wider range of tumor subtypes than commercially available proteasome inhibitors and presents a new candidate for future studies.     

Enantioselective Platinum‐Catalyzed Silicon‐Boron Addition to 1,3‐Cyclohexadiene

Silaboration of 1,3‐cyclohexadiene in the presence of Pt(acac)₂, DIBALH, and a phosphoramidite prepared from (S)‐1,1′‐bi‐2‐naphthol and diisopropylamine led to (1R,4S)‐1‐(dimethylphenylsilyl)‐4‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl)‐2‐cyclohexene with 70% ee. Chiral catalysts based on Ni gave no or essentially racemic product, whereas complexes containing Pd were inactive.     

Enzymes in Organic Chemistry, 11:[1] Hydrolase‐Catalyzed Resolution of α‐ and β‐Hydroxyphosphonates and Synthesis of Chiral,Non‐Racemic β‐Aminophosphonic Acids

The enantioselective acylation of racemic diisopropyl α‐ and β‐hydroxyphosphonates by hydrolases in t‐butyl methyl ether with isopropenyl acetate as acyl donor is limited by the narrow substrate specificity of the enzymes. High enantiomeric excesses (up to 99%) were obtained for the acetates of (S)‐diisopropyl 1‐hydroxy‐(2‐thienyl)methyl‐, 1‐hydroxyethyl‐ and 1‐hydroxyhexylphosphonate and (R)‐diisopropyl 2‐hydroxypropylphosphonate. The hydrolysis of a variety of β‐chloroacetoxyphosphonates by the lipase from Candida cylindracea and protease subtilisin in a biphasic system gives (S)‐β‐hydroxyphosphonates (ee 51–92%) enantioselectively. (S)‐2‐Phenyl‐2‐hydroxyethyl‐ and (S)‐3‐methyl‐2‐hydroxybutylphosphonates (ee 96% and 99%, respectively) were transformed into (R)‐2‐aminophosphonic acids of the same ee.     

Synthesis of Diastereomeric 1,4‐Diphosphine Ligands Bearing Imidazolidin‐2‐one Backbone and Their Application in Rh(I)‐Catalyzed Asymmetric Hydrogenation of Functionalized Olefins

The diastereomeric 1,4‐diphosphine ligands, (S,S,S,S)‐ 1a , (R,S,S,R)‐ 1b and (R,S,S,S)‐ 1c , with the imidazolidin‐2‐one backbone were synthesized, and utilized for an investigation of the effects of backbone chirality on the enantioselectivity in the Rh(I)‐catalyzed hydrogenation of various functionalized olefinic substrates. It was found that the catalytic efficiencies are largely dependent on the configurations of the α‐carbons to phosphine. Thus, the Rh complex of the pseudo‐C₂‐symmetrical diphosphine, (R,S,S,S)‐ 1c , showed excellent enantioselectivities (93.0–98.6% ees) in the hydrogenations of a broad spectrum of substrates, and especially in the hydrogenations of methyl α‐(N‐acetyamino)‐β‐arylacrylates (95.3–97.0% ees). However, the enantioselectivities obtained with the C₂‐symmetrical (R,S,S,R)‐ 1b were largely dependent on the substrate (19.8–97.3% ees). The Rh complex of ligand 1a having the (S,S,S,S)‐configuration showed the lowest catalytic efficiency for all of the substrates examined (0–84.8% ees).     

Blending ultrahigh‐molecular‐weight polyethylene and poly(ethylene/10‐undecen‐1‐ol) in one nascent particle

Ultrahigh‐molecular‐weight polyethylene (UHMWPE)/polar polyethylene (PE) composites were blended in one nascent particle by in situ polymerization with a hybrid catalyst. Polystyrene‐coated SiO₂ particles were used to support the hybrid catalyst. Fe(acac)₃/2,6‐bis[1‐(2‐isopropylanilinoethyl)] was supported on SiO₂ for the synthesis of UHMWPE, whereas [PhN?C(CH₃)CH?C(Ph)O]VCl₂ was immobilized on a polystyrene layer to prepare a copolymer of ethylene and 10‐undecen‐1‐ol (polar PE). Importantly, the core part of the supports (the polystyrene layer) exhibited pronounced transfer resistance to 10‐undecen‐1‐ol; this provided an opportunity to keep the inside iron active sites away from the poisoning of 10‐undecen‐1‐ol. Therefore, UHMWPE was simultaneously synthesized with polar PE by in situ polymerization. Interestingly, the morphological results show that UHMWPE and the polar PE were successfully blended in one nascent polymer. This improved the miscibility of the composites, where most of the chains were difficult to crystallize because of the strong interactions between the PE chains and polar chains. The blends showed an extremely low crystallinity, that is, 9.9%. Finally, the hydrophilic properties of the polymer composites were examined. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46652.     

Highly trans‐1,4‐specific polymerization of 1,3‐butadiene catalyzed by [2,6‐bis{(4S)‐ (−)‐isopropyl‐2‐oxazolin‐2‐yl}pyridine] chromium complex activated with modified methylaluminoxane

Chromium complexes with N,N,N‐tridentate ligands, LCrCl₃ (L = 2,6‐bis{(4S)‐(?)‐isopropyl‐2‐oxazolin‐2‐yl}pyridine ( 1 ), 2,2′:6′,2″‐terpyridine ( 2 ), and 4,4′,4″‐tri‐tert‐butyl‐2,2′:6′,2″‐terpyridine ( 3 )), were prepared. The structures of 1 and 2 were determined by X‐ray crystallography. Upon activation with modified methylaluminoxane (MMAO), 1 catalyzed the polymerization of 1,3‐butadiene, while 2 and 3 was inactive. The obtained poly(1,3‐butadiene) obtained with 1 ‐MMAO was found to have completely trans‐1,4 structure. The 1 ‐MMAO system also showed catalytic activity for the polymerization of isoprene to give polyisoprene with trans‐1,4 (68%) and cis‐1,4 (32%) structure. Copyright © 2011 Society of Chemical Industry     

Synthesis of novel polymethacrylate bearing an (S)‐(+)‐1‐cyclohexylethyl urea group in the side chain and its chiral recognition ability

A new chiral methacrylate, (S)‐(+)‐1‐cyclohexylethyl‐(2‐methacryloyloxyethyl)urea (CEMOU), was synthesized from 2‐methacryloyloxyethyl isocyanate (MOI) and (S)‐(+)‐cyclohexylethylamine. Radical homopolymerization of CEMOU was performed in several solvents to obtain the corresponding chiral polymers having hydrogen bonds based on urea moieties. Specific optical rotations of poly(CEMOU) were slightly changed by the measurement temperature, which may be attributed in part to a change of conformation caused by hydrophobic interaction between the cyclohexyl groups. From the results of radical copolymerization of CEMOU (M₁) with styrene (ST, M₂) or methyl methacrylate (MMA, M₂), monomer reactivity ratios (r₁, r₂) and Alfrey–Price Q–e values were determined: r₁ = 0.89, r₂ = 0.12, Q₁ = 2.45, e₁ = 0.68 for the CEMOU–ST system; r₁ = 0.48, r₂ = 0.18, Q₁ = 8.39, e₁ = 1.97 for the CEMOU–MMA system. The chiroptical property of the poly(CEMOU‐co‐ST) was slightly influenced by the co‐units. Poly(CEMOU)‐bonded silica gel as the chiral stationary phase (CSP) was prepared for high‐performance liquid chromatography (HPLC). The CSP resolved trans‐2‐dibenzyl‐4,5‐di(o‐hydroxyphenyl)‐1,3‐dioxolane in normal phase such as n‐hexane/2‐propanol by HPLC. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1018–1025, 2003     

Discovery of α‐Substituted Imidazole‐4‐acetic Acid Analogues as a Novel Class of ρ1 γ‐Aminobutyric Acid Type A Receptor Antagonists with Effect on Retinal Vascular Tone

The ρ‐containing γ‐aminobutyric acid type A receptors (GABA_ARs) play an important role in controlling visual signaling. Therefore, ligands that selectively target these GABA_ARs are of interest. In this study, we demonstrate that the partial GABA_AR agonist imidazole‐4‐acetic acid (IAA) is able to penetrate the blood–brain barrier in vivo; we prepared a series of α‐ and N‐alkylated, as well as bicyclic analogues of IAA to explore the structure–activity relationship of this scaffold focusing on the acetic acid side chain of IAA. The compounds were prepared via IAA from l ‐histidine by an efficient minimal‐step synthesis, and their pharmacological properties were characterized at native rat GABA_ARs in a [³H]muscimol binding assay and at recombinant human α₁β₂γ_2S and ρ₁ GABA_ARs using the FLIPR? membrane potential assay. The (+)‐α‐methyl‐ and α‐cyclopropyl‐substituted IAA analogues ((+)‐ 6 a and 6 c , respectively) were identified as fairly potent antagonists of the ρ₁ GABA_AR that also displayed significant selectivity for this receptor over the α₁β₂γ_2S GABA_AR. Both 6 a and 6 c were shown to inhibit GABA‐induced relaxation of retinal arterioles from porcine eyes.     

Unusual Totally Selective Cyclodimerization of Epoxides: Synthesis of a Pair of Diastereoisomers of Enantiopure 2,5‐Disubstituted‐1,4‐Dioxanes with C2 Symmetry

The synthesis of the C₂‐symmetrical (2R,5R)‐ and (2S,5S)‐2,5‐bis‐[(S)‐1‐(dibenzylaminoalkyl)]‐1,4‐dioxanes 1 or 2 in enantiopure form is reported. Compounds 1 and 2 were obtained by a completely selective and unusual cyclodimerization of chiral (2R,1′S)‐ or (2S,1′S)‐2‐(1‐aminoalkyl)epoxides 3 or 4 promoted by a mixture of diisopropylamine and boron trifluoride⋅diethyl etherate complex. The structure of the obtained dioxane was established by single‐crystal X‐ray diffraction analysis. A mechanism has been proposed to explain this transformation.     

siRNA Modified with 2′‐Deoxy‐2′‐C‐methylpyrimidine Nucleosides

(2′S)‐2′‐Deoxy‐2′‐C‐methyluridine and (2′R)‐2′‐deoxy‐2′‐C‐methyluridine were incorporated in the 3′‐overhang region of the sense and antisense strands and in positions 2 and 5 of the seed region of siRNA duplexes directed against Renilla luciferase, whereas (2′S)‐2′‐deoxy‐2′‐C‐methylcytidine was incorporated in the 6‐position of the seed region of the same constructions. A dual luciferase reporter assay in transfected HeLa cells was used as a model system to measure the IC₅₀ values of 24 different modified duplexes. The best results were obtained by the substitution of one thymidine unit in the antisense 3′‐overhang region by (2′S)‐ or (2′R)‐2′‐deoxy‐2′‐C‐methyluridine, reducing IC₅₀ to half of the value observed for the natural control. The selectivity of the modified siRNA was measured, it being found that modifications in positions 5 and 6 of the seed region had a positive effect on the ON/OFF activity.     

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.     

Benzothiazole‐accelerated sulfur vulcanization. I. 2‐Mercaptobenzothiazole as accelerator for 2,3‐dimethyl‐2‐butene

2,3‐Dimethyl‐2‐butene (TME) was used as a model compound for polyisoprene in a study of 2‐mercaptobenzothiazole (MBT)‐accelerated sulfur vulcanization. Mixes that contained curatives only were heated in a DSC to various temperatures, while those that also contained TME were heated isothermally at 150°C in evacuated, sealed glass ampules. Heated mixtures were analyzed for residual curatives, intermediates, and reaction products by HPLC. It is proposed that MBT forms polysulfidic species (BtS_xH) in the presence of sulfur and that these react with TME via a concerted, substitutive reaction pathway to form polysulfidic hydrogen‐terminated pendent groups of varying sulfur rank (TME–S_xH). MBT is released as a by‐product of this reaction. Crosslinking occurs slowly as a result of the interaction of polythiol pendent groups, the rate being dependent on the pendent group concentration. H₂S is released on crosslinking. 2,3‐Dimethyl‐2‐butene–1‐thiol was synthesized and reacted in the presence of sulfur to confirm the formation of crosslinked products (TME–S_x–TME). Benzothiazole‐terminated pendent groups (TME–S_xBt) were not observed. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 1377–1385, 2000     

Highly Regioselective DABCO‐Catalyzed Nucleophilic Aromatic Substitution (SNAr) Reaction of Methyl 2,6‐Dichloronicotinate with Phenols

Exclusive formation of 6‐aryloxy ethers 9 from an S_NAr reaction of methyl 2,6‐dichloronicotinate ( 2 ) with phenols 7 catalyzed by 1,4‐diazabicyclo[2.2.2]octane (DABCO) in the presence of stoichiometric triethylamine is described. The reaction proceeds via the regioselective formation of an unprecedented DABCO‐pyridine adduct 10a .     

Biological stereoselective reduction of 2,6‐ and 3,5‐dimethylcyclohexanones by Glomerella cingulata

The microbial transformations of 2,6‐ and 3,5‐dimethylcyclohexanone were investigated using the plant pathogenic fungus, Glomerella cingulata. With this organism 2,6‐ and 3,5‐dimethylcyclohexanone gave the corresponding 2,6‐ and 3,5‐dimethylcyclohexanol. The metabolites from 2,6‐dimethylcyclohexanone indicated enantioselective reduction by specific optical rotation of the products. The enantiomeric excesses of the microbiological reduction products were determined by ¹H‐NMR spectra of (+)‐MTPA‐esters of the alcohols produced. The reduction of 2,6‐dimethylcyclohexanone was stereospecific, with the (2R,6R)‐ketone being converted to the corresponding (2R,6R)‐(−)‐2,6‐dimethylcyclohexanol; absolute configuration, 70% ee. On the other hand, 3,5‐dimethylcyclohexanone gave the (1α,3α,5α)‐3,5‐dimethylcyclohexanol (74%) and (1α,3β,5β)‐3,5‐dimethylcyclohexanol (26%). © 1999 Society of Chemical Industry