26744-15-0

Disclosed are a novel diacylglycerol lactone compound for improving immunity and inhibiting infection by promoting neutrophil movement, a preparation method therefor, and an immunostimulator containing same as an active ingredient. The diacyloglycerol lactone compound is represented by chemical formula 1 of the specification. In chemical formula 1, R1 and R2 are respectively N and independently a C2-30 fatty acid group.

In the search for novel aromatase inhibitors, a series of triazole and imidazole-based carbamate derivatives were designed and synthesized. Final compounds were thus evaluated against human aromatase by in vitro kinetic experiments in a fluorimetric assay in comparison with letrozole. The effect of most active derivatives 13a and 15c was then evaluated in vitro on the human breast cancer cell line MCF7 by MTT assay, cytotoxicity assay (LDH release) and cell cycle analysis, revealing a dose-dependent inhibition profile of cell viability and low micromolar IC50 values. In addition, docking simulations were also carried out to elucidate at a molecular level of detail the binding modes adopted to target human aromatase.

The invention relates to the field of medicinal chemistry, in particular to a substituted diaryl compound (I). The preparation method comprises the following steps: medicine preparation and medical application thereof. Test results show that the substituted diaryl compound has a good inhibition effect on human lung cancer (A549), human ovarian cancer (SKOV3), human melanoma (A375) and human colon cancer (LOVO) cells. Formula (I):

A chiral metal-organic framework possessing an open amphiphilic channel is constructed from a dicarboxylate ligand derived from an amino acid and is shown to be an efficient and recyclable chiral solid adsorbent, which is capable of separating racemic secondary alcohols, epoxides, and ibuprofen with very high enantioselectivity.

The chemoselective synthesis of 2-(phenoxymethyl)oxirane from allyloxybenzene is achieved with over 90 % yield in a sustainable reaction system using titanium-substituted silicalite-1 (TS-1) as a catalyst, hydrogen peroxide (H2O2) as an oxidant, and a mixture of MeOH/MeCN as a solvent at 40 °C. No acid-catalyzed side reactions prompted by the Lewis acidity of the Ti active site in TS-1 are observed. The TS-1 catalyst can also promote the formation of oxiranes from various p-substituted allyloxybenzenes in good yields. The reaction mechanism is investigated through the reaction with other allyloxy compounds. The results, which are supported by DFT calculations, indicate that an active species of Ti peroxides formed from the reaction of TS-1 with H2O2 selectively oxidizes the allyloxybenzene to 2-(phenoxymethyl)oxirane.

To improve the anti-inflammatory activity of desloratadine, we designed and synthesized a series of novel desloratadine derivatives. All compounds were evaluated for their anti-inflammatory and H1 antagonistic activities. Among them, compound 2c showed the strongest H1 antagonistic and anti-inflammatory activity. It also exhibited promising pharmacokinetic profiles and low toxicity. All these results suggest that compound 2c as a novel anti-allergic agent is worthy of further investigation.

A facile and efficient method has been developed for synthesis of β-iodocarboxylates in the presences of Ph3P/I2. Starting from epoxides, a series of β-iodocarboxylate compounds can be directly obtained in toluene media with excellent yields. Moreover, the method was successfully applied for the late-stage modification of natural products, such as isosteviol and vincamine derivatives, achieving the corresponding β-iodocarboxylates in good yields.

Compounds with activity as modulators of cell adhesion are disclosed. The compounds are derivatives of piperidin-4-amine. In some embodiments, a compound can be linked to a targeting agent, a pharmaceutically active substance and/or a support material. Methods for enhancing or inhibiting classical cadherin-mediated functions are also disclosed. The compounds can be used for the treatment or prevention of a variety of diseases including cancer. Compositions and devices, including skin patches comprising a compound are also disclosed. In addition, methods of synthesis of the compounds are provided.

Chiral binaphthyl-strapped Zn(II) porphyrins with triazolium halide units were synthesized as bifunctional catalysts for kinetic resolution of epoxides with CO2. Several catalysts were screened by changing the linker length and nucleophilic counteranions, and the optimized catalyst accelerated the enantioselective reaction at ambient temperature to produce optically active cyclic carbonates and epoxides.

A series of β‐hydroxyazides were effectively synthesized from the regioselective ring opening of epoxides by sodium azide using montmorillonite K10 as a novel heterogeneous catalyst in aqueous acetonitrile in good to excellent yields. The utility of this method has been demonstrated by achieving a short synthesis of phenylglycine in 33.5% overall yield.

(2,3-Dihydrobenzo[b][1,4]oxathiin-3-yl)methanols were synthesized via reactions of aryloxymethylthiiranes and N-bromosuccinimide (NBS) in DMSO under microwave irradiation. The reaction mechanism was proposed as an intramolecular aromatic electrophilic substitution of 1-bromo-2-(aryloxymethyl)thiiran-1-iums, generated from aryloxymethylthiiranes and NBS, and the subsequent DMSO nucleophilic ring opening reaction of thiiran-1-iums followed by the water displacement. The current method provides a direct and simple strategy in the efficient preparation of (2,3-dihydrobenzo[b][1,4]oxathiin-3-yl)methanols from readily available aryloxymethylthiiranes.

A series of propanones containing combinations of aryloxy and alkoxy substituents at the 1- and 3-positions were reduced to the alcohols via asymmetric transfer hydrogenation using a tethered Ru(II)/TsDPEN catalyst. The enantioselectivities of the reductions reveal a complex pattern of electronic and steric effects which, when used in a matched combination, can lead to the formation of products of up to 68% ee (84:16 er) from this highly challenging class of substrate.

An efficient synthesis of β-amino alcohols from a variety of epoxides and primary unbranched amines in the absence of any catalyst in high yields and regioselectivities is reported. A variety of polar mixed solvent systems allow for the selective formation of secondary amino alcohols over tertiary amino alcohols. The reaction scope extends to a wide variety of aromatic and aliphatic substituted epoxides and primary amines bearing complex functionality.

New chiral macrocyclic cobalt(III) salen complexes were synthesized and used as catalyst for the asymmetric kinetic resolution (AKR) of terminal epoxides and glycidyl ethers with aromatic/aliphatic amines and water as nucleophiles. This is the first occasion where a Co(III) salen complex demonstrated its ability to catalyze AKR as well as hydrolytic kinetic resolution (HKR) reactions. Excellent enantiomeric excesses of the epoxides, the corresponding amino alcohols and diols (upto 99%) with quantitative yields were achieved by using the chiral Co(III) salen complexes in dichloromethane at room temperature. This protocol was further extended for the synthesis of two important drug molecules, i.e., (S)-propranolol and (R)-naftopidil. The catalytic system was also explored for the synthesis of chirally pure diols and chiral cyclic carbonates using carbon dioxide as a greener renewable C1 source. The catalyst was recycled for upto 5 catalytic cycles with retention of enantioselectivity. (Figure presented.).

Among chiral macrocycles 1 synthesized, 1m with the 3,5-bis(trifluoromethyl)phenylethynyl group was the best organocatalyst for the enantioselective synthesis of cyclic carbonates from disubstituted or monosubstituted epoxides and CO2. The X-ray crystal structure of 1m revealed a well-defined chiral cavity with multiple hydrogen-bonding sites that is suitable for the enantioselective activation of epoxides. A catalytic cycle proposed was supported by DFT calculations.

The design, synthesis and biological study of several novel 1,2,3-triazolyl β -hydroxy alkyl/carbazole hybrid molecules as a new type of antifungal agent has been described. In this synthesis, the N-alkylation reaction of carbazol-9-ide potassium salt with 3-bromoprop-1-yne afforded 9-(prop-2-ynyl)-9H-carbazole. The ‘Click’ Huisgen cycloaddition reaction of 9-(prop-2-ynyl)-9H-carbazole with diverse β -azido alcohols in the presence of copper-doped silica cuprous sulphate led to target molecules in excellent yields. The in vitro antifungal and antibacterial activities of title compounds were screened against various pathogenic fungal strains, Gram-positive and/or Gram-negative bacteria. In particular, 1-(4-((9H-carbazol-9-yl) methyl)-1H-1,2,3-triazol-1-yl)-3-butoxypropan-2-ol (10e) proved to have potent antifungal activity against all fungal tests compared with fluconazole and clotrimazole as studied reference drugs. Our molecular docking analysis revealed an appropriate fitting and a potential powerful interaction between compound 10e and an active site of the Mycobacterium P450DM enzyme. The strong hydrogen bondings between β -hydroxyl and ether groups in 10e were found to be the main factors that drive the molecule to fit in the active site of enzyme. The in silico pharmacokinetic studies were used for a better description of 10a–10n as potential lead antifungal agents for future investigations.

A novel class of NaV1.7 inhibitors has been identified by high-throughput screening followed by structure activity relationship studies. Among this series of compounds, piperidine 9o showed potent human and mouse NaV1.7 inhibitory activities with fair subtype selectivity over NaV1.5. Compound 9o successfully demonstrated analgesic efficacy in mice comparable to that of the currently used drug, mexiletine, but with an expanded central nervous system safety margin.

In the search for a novel serotonin 7 (5-HT7) receptor PET radioligand we synthesized and evaluated a new series of biphenylpiperazine derivatives in vitro. Among the studied compounds, (R)-1-[4-[2-(4-methoxyphenyl) phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol ((R)-16), showed the best combination of affinity, selectivity, and lipophilicity, and was thus chosen for carbon-11 labelling and evaluation in pigs. After intravenous injection, [11C](R)-16 entered the pig brain and displayed reversible tracer kinetics. Pretreatment with the 5-HT7receptor selective antagonist SB-269970 (1) resulted in limited decrease in the binding of [11C](R)-16, suggesting that this radioligand is not optimal for imaging the brain 5-HT7receptor in vivo but it may serve as a lead compound for the design of novel 5-HT7receptor PET radioligands.

The invention relates to a new class of compounds able to inhibit with high affinity and selectivity the 5-HT7 receptor. The invention also relates to the utilization of such compounds as medicaments useful in the treatment and prevention of 5-HT7 receptor relating disorders of the central nervous system. The invention also relates to the isotopically labeled compounds for use in vivo diagnosis or imaging of a 5-HT7 condition.

A series of chiral polymeric Co(iii)-salen complexes based on a number of achiral and chiral linkers were synthesized and their catalytic performances were assessed in the asymmetric hydrolytic kinetic resolution of terminal epoxides. The effects of the linker were judiciously studied and it was found that in the case of the chiral BINOL-based polymeric salen complex 1, there was an enrichment in catalyst reactivity and enantioselectivity of the unreacted epoxide, particularly in the case of short as well as long chain aliphatic epoxides. Good isolated yields of the unreacted epoxide (up to 46% compared to 50% theoretical yield) along with high enantioselectivity (up to 99%) were obtained in most cases using catalyst 1. Further studies showed that catalyst 1 could retain its catalytic activity for six cycles under the present reaction conditions without any significant loss in activity or enantioselectivity. To show the practical applicability of the above synthesized catalyst we have synthesised some potent chiral β-blockers in moderate yield and high enantioselectivity using complex 1. The DFT (M06-L/6-31+G??//ONIOM(B3LYP/6-31G?:STO-3G)) calculations revealed that the chiral BINOL linker influences the enantioselectivity achieved with Co(iii)-salen complexes. Further, the transition state calculations show that the R-BINOL linker with the (S,S)-Co(iii)-salen complex is energetically preferred over the corresponding S-BINOL linker with the (S,S)-Co(iii)-salen complex for the HKR of 1,2-epoxyhexane. The role of non-covalent C-H?π interactions and steric effects has been discussed to control the HKR reaction of 1,2-epoxyhexane.

An efficient method for the conversion of oxiranes to thiiranes by treatment with excess ammonium thiocyanate in aqueous media under reflux or by microwave irradiation is reported. ARKAT-USA, Inc.

The invention relates to a new class of compounds able to inhibit with high affinity and selectivity the 5-HT7 receptor. The invention also relates to the utilization of such compounds as medicaments useful in the treatment and prevention of 5-HT7 receptor relating disorders of the central nervous system. The invention also relates to the isotopically labeled compounds for use in vivo diagnosis or imaging of a 5-HT7 condition.

A screen of aryloxy aminopropanol organocatalysts derived from the β-blocker inhibitor S-timolol determined the most active catalyst of asymmetric α-hydroxylation of β-keto esters. (R)-1-(tert-butylamino)- 3-(3,4,5-trimethoxyphenoxy) propan-2-ol (3k) was the most effective derivative, enantioselectively catalyzing α-hydroxylation of β-keto esters using tert-butyl hydroperoxide as the oxidant in hexane to afford the corresponding products in excellent yield and with good enantioselectivity (up to 96% yield, 88% ee).

Chiral nanoporous metal-organic frameworks are constructed by using dicarboxyl-functionalized chiral Ni(salen) and Co(salen) ligands. The Co(salen)-based framework is shown to be an efficient and recyclable heterogeneous catalyst for hydrolytic kinetic resolution (HKR) of racemic epoxides with up to 99.5% ee. The MOF structure brings Co(salen) units into a highly dense arrangement and close proximity that enhances bimetallic cooperative interactions, leading to improved catalytic activity and enantioselectivity in HKR compared with its homogeneous analogues, especially at low catalyst/substrate ratios.

The 'click synthesis' of some novel O-substituted oximes, 7a-7t, which contain 1,2,3-triazolediyl residues, as new analogs of β-adrenoceptor antagonists is described (Schemes 1-4). The synthesis of these compounds was achieved in four to five steps. The formation of oximes of 9H-fluoren-9-one and benzophenone, i.e., 9a and 9b, respectively, followed by their reaction with propargyl bromide, afforded O-propargyl oximes 10a and 10b, respectively, which by a subsequent CuI-catalyzed Huisgen cycloaddition with prepared β-azido alcohols 11a-11j (Schemes 2 and 3), led to the target compounds 7a-7t in good yields. Copyright

Oxidation of 2-(aryloxymethyl)oxiranes with periodic acid gave a series of aryloxyacetaldehydes which reacted with cyclohexylamine in THF, and subsequent reduction of Schiff bases thus obtained with sodium tetrahydridoborate resulted in the formation of the corresponding secondary amines which were isolated and characterized as hydrochlorides.

A compound, composition and method are disclosed that can provide analgesia. A contemplated compound has a structure that corresponds to Formula A, wherein A, B, X, R1, R2, R7 and R8, and the dashed lines are defined within.

Using a vHTS based on a pharmacophore alignment on known β3-adrenoceptor ligands, a set of intriguing β-adrenoceptor ligands was identified, optimization of which resulted in a selective and potent human β2-AR antagonist.

Resulting from a vHTS based on a pharmacophore alignment on known β3-adrenoceptor ligands, an aryloxypropanolamine scaffold comprising a thienopyrimidine moiety was further optimized as a human β3-AR agonist, yielding a lead compound with an excellent cellular activity of EC50 = 20 pM, selectivity over hβ1- and hβ2-adrenoceptors and a promising safety profile.

Directed evolution of enzymes as enantioselective catalysts in organic chemistry is an alternative to traditional asymmetric catalysis using chiral transition-metal complexes or organocatalysts, the different approaches often being complementary. Moreover, directed evolution studies allow us to learn more about how enzymes perform mechanistically. The present study concerns a previously evolved highly enantioselective mutant of the epoxide hydrolase from Aspergillus niger in the hydrolytic kinetic resolution of racemic glycidyl phenyl ether. Kinetic data, molecular dynamics calculations, molecular modeling, inhibition experiments, and X-raystructural work for the wild-type (WT) enzyme and the best mutant revea l the basis of the large increase in enantioselectivity (E = 4.6 versus E = 115). The overall structures of the WT and the mutant are essentially identical, but dramatic differences are observed in the active site asrevealed by the X-ray structures. All of the experimental and computati onal results support a model in which productive positioning of the preferred (S)-glycidyl phenyl ether, but not the (R)-enantiomer, forms the basis of enhanced enantioselectivity. Predictions regarding substrate scope and enantioselectivity of the best mutant are shown to be possible.

The expedient synthesis of enantiopure masked 1,2-amino alcohols (ee >99%) including their alkyl substituted analogues has been achieved by the regioselective ring opening of epoxides using phthalimide, followed by highly efficient kinetic resolution under mild and environmentally friendly conditions. The addition of co-solvents during kinetic resolution significantly improved the enantioselectivity with reduction in time.

The enantioselective chemical fixation of CO2 into an epoxide was developed using an optically active ketoimi-natocobalt(II) complex as a chiral Lewis acid. In the presence of a catalytic amount of the cobalt complex and amine base, enantioselective CO2 fixation with an epoxide proceeded with kinetic resolution to afford the corresponding carbonate along with unreacted epoxide, both of which were optically active. To improve their enantioselectivities, the ligand structures of the cobalt complexes and amine bases were examined. Thus, the optimized catalytic system was successfully applied to various epoxides to obtain the corresponding optically active cyclic carbonates and to recover epoxides with good-to-high enantioselectivities.

An atom economic, selective, and highly practical two-metal one-pot synthesis of heterocycles has been developed that efficiently affords enantio- and diastereopure N- and O-heterocyclic products. Furthermore, use of a chiral catalyst in the two-metal procedure allows formation of all possible diastereomers, even those that are traditionally difficult to access via cyclization routes due to thermodynamics. Interestingly, the nature of the enantiodiscriminating event differs between the use of amine versus alcohol nucleophiles. The method also affords heterocyclic products that are synthetically useful intermediates. Through the Z-vinylsilane a variety of stereodefined trisubstituted olefin products can be accessed including several all-carbon motifs. Finally, the utility of these heterocyclic products in total synthesis is demonstrated through concise syntheses of a kainoid intermediate, a constituent of oil of rose, and the ring B portion of bryostatin, a potent chemotherapeutic.

Several epoxides are efficiently converted to the corresponding β-chlorohydrins in impressive yields with thionyl chloride in the presence of β-cyclodextrin using water as solvent at room temperature. Copyright Taylor & Francis, Inc.

A convenient preparation of the (R)- and (S)-enantiomers of O-(4-methoxyphenyl)-glycidol by a one-pot reduction of ketone 3 and in situ lipase mediated resolution is described. Activated moist aluminium oxide in the presence of Pseudomonas cepacia lipase immobilized on ceramic particles (PS-C) has been found effective for the transesterification leading to a high degree of enantioselectivity. These chiral glycidols were further used as a chiral precursor for the synthesis of biologically important 1,2-O-diacyl-sn-glycerol under mild reaction conditions. The present method is facile for the synthesis of chiral glycidols in high enantioselectivity when compared to the previously reported methods.

A process for producing a glycidyl ether and an optically active compound thereof with high yield and an optically high purity comprising reacting an alcohol with epihalohydrin in a base to thereby produce a glycidyl ether, the reaction performed in a two-layer system of a nonaqueous organic solvent and an aqueous solvent.

Substituted aryloxypropanolamines (6-20) were synthesized and evaluated for their anorexigenic activity. Among them 4-cyanoaryloxy (7), 2-methylaryloxy (9), 2-methoxyl aryloxy (10), 4-acetamidoaryloxy (15), 4-bromoaryloxy (16) and 4-ethylaminoaryloxy (20) exhibited potent anorexigenic activity. According to QSAR studies, the electronic parameter 'σ' plays an important role in describing the variance in activity. Birkhaeuser Boston 2004.

The enantioselective partial hydrolysis of a number of racemic aryl glycidyl ethers in the presence of chiral Co(salen)-catalyst was studied. The enantiomeric composition of the isolated (R)-aryl glycidyl ethers was analyzed by 31P NMR using optically active substituted 2-chloro-1,3,2- dioxaphospholanes. A synthesis of β-adrenoblocking agents (S)-toliprolol and (S)-moprolol based on the simultaneously obtained (S)-3-aryloxypropane-1,2- diols was proposed.

Disclosed are novel heterocyclic derivatives, useful for the treatment of various disease states, in particular cardiovascular diseases such as atrial and ventricular arrhythmias, intermittent claudication, Prinzmetal's (variant) angina, stable and unstable angina, exercise induced angina, congestive heart disease, and myocardial infarction. The compounds are also useful in the treatment of diabetes, and for increasing HDL plasma levels in mammals.

wherein: a.o. T is oxygen, sulfur, or NR11 , in which R11 is hydrogen or lower alkyl; V is -N1 is hydrogen, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; X2 is optionally substituted aryl or optionally substituted heteroaryl; Y is optionally substituted dihydroheteroarcyl; and Z1 and Z2 are independently optionally substituted alkylene of 1-4 carbon atoms, useful for the treatment of various disease states, in particular cardiovascular diseases such as atrial and ventricular arrhythmias, intermittent claudication, Prinzmetal’s (variant) angina, stable and unstable angina, exercise induced angina, congestive heart disease, and myocardial infarction. The compounds are also useful in the treatment of diabetes.

A practical second-generation synthesis of an advanced intermediate in our total synthesis of altohyrtin C (spongistatin 2) has been developed. A new approach to the C1-C15 (AB) portion features a vinyllithium addition to an aldehyde followed by a palladium-catalyzed allylic reduction to install the troublesome C13-C15 segment. Our general approach to the C16-C28 (CD) spiroketal has been retained, but some improvements have been made. Most notably, the kinetically controlled CD-spiroketalization reaction now proceeds in high yield with excellent diastereoselection. This new strategy uses the anti-aldol coupling used in our first-generation synthesis to join AB and CD fragments. A total of 9.6 g of intermediate 57 has been produced using this improved route.

Disclosed are novel heterocyclic derivatives, useful for the treatment of various disease states, in particular cardiovascular diseases such as atrial and ventricular arrhythmias, intermittent claudication, Prinzmetal's (variant) angina, stable and unstable angina, exercise induced angina, congestive heart disease, and myocardial infarction. The compounds are also useful in the treatment of diabetes, and for increasing HDL plasma levels in mammals.

We synthesized a novel series of 21 aryloxypropanolamine compounds characterized by N-alkyl, aralkyl, and aryl substituents. The compounds showed potent β3-adrenergic agonistic activities in Chinese hamster ovary cells expressing the bovine β3-adrenoceptors with Kact and Ki values of 4.2 ± 3.0 nM and 459 ± 169 nM respectively, for the ligand with the best compromise between potency and affinity. Structure-activity relationships are discussed.

(Matrix presented) The synthesis of the C1-C12 fragment of fostriecin was achieved from (S)-glycidol in 15 steps by using an enantioselective allytitanation reaction and a ring-closure metathesis as the key steps.

Incorporation of the flexible amino acid β-alanine (β) into hairpin polyamides composed of N-methylpyrrole (Py) and N-methylimidazole (Im) amino acids is required for binding to DNA sequences longer than seven base pairs with high affinity and sequence selectivity. Pairing the α-substituted-β- amino acids (S)-isoserine ((S)Is), (R)-isoserine ((R)Is), β-aminoalanine (Aa), and α-fluoro-β-alanine (Fb) side-by-side with β in hairpin polyamides alters DNA binding affinity and selectivity relative to the parent polyamide containing a β/β pairing. Quantitative DNase I footprinting titration studies on a restriction fragment containing the sequences 5'- TGCNGTA-3' (N = A, T, G, and C) show that the polyamide ImPy(S)IsImPy-γ- PyPyβImPy-β-Dp (S)Is/β pairing) binds to N = T (K(a) = 4.5 x 109 M-1) in preference to N = A (K(a) = 6.2 x 108 M-1). This result stands in contrast to the essentially degenerate binding of the parent ImPyβImPy-γ- PyPyβImPy-β-Dp (β/β pairing) to N = T and N = A, and to the slight preference of ImPyβImPy-γ-PyPy(S)IsImPy-β-Dp (β/(S)Is pairing) to N = A over N = T. Additionally, this study reveals that incorporation of (R)Is, Aa, and Fb into polyamides significantly reduces binding affinity. Therefore, DNA binding in the minor groove is sensitive to the stereochemistry, steric bulk, and electronics of the substituent at the α-position of β-amino acids in hairpin polyamides containing β/β pairs.

A cloned human β3 adrenergic receptor assay was used to identify potent and selective β3 agonists. The thiazolidinedione moiety has been identified as a new pharmacophore for the human β3 adrenergic receptor. The versatility of the thiazolidinedione pharmacophore was demonstrated in both the arylethanolamine and phenylpropanolamine families of β3 agonists, where potent and selective compounds have been synthesized. Thiazolidinedione 20, a potent and selective human β3 agonist, increased thermogenesis and lowered plasma glucose levels in the db/db mice.

(Matrix presented) An efficient synthesis of the C1-C14 fragment of amphotericin B is described. This synthesis is based on the formation of syn-1,3-diols from enantioselective allyltitanation of unprotected β-hydroxyaldehydes.

The two modes of the paths in the reaction of oxiranes with phenols are completely controlled by CsF. Glycidyl nosylate undergoes exclusive substitution at the C1 position whereas the ring-opening (C-3 attack) occurs with epichlorohydrin, glycidol, and 1,2-epoxyalkanes. These reactions provide convenient access to enantiopure β-blockers.

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(R)-3-Deoxysphingomyelin (2) was prepared from (S)-1-(4′-methoxyphenyl)-glycerol (3). The latter was converted into either p-methoxyphenyl (PMP) (S)-oxiranylmethyl ether (5) or (R)-1-(4′-methoxyphenyl)glycerol 2,3-cyclic sulfate (6). Opening of 5 with lithium pentadecyne in the presence of BF3·Et2O gave PMP (S)-2-hydroxy-4-octadecynyl ether (7) in 65percent yield. Alternatively, opening of cyclic sulfate 6 with excess lithium pentadecyne in the presence of catalytic cuprous iodide, followed by acidic workup, gave 7 in 90percent yield. After introduction of the amide group via azide displacement, reduction, and N-acylation, simultaneous reduction of the triple bond and deprotection of the PMP group by Birch reduction (Li, EtNH2) provided 3-deoxy-N-palmitoyl-(A)-ceramide (9). Finally, phosphitylation of 9, oxidation of the cyclic phosphite with bromine, followed by in situ ring opening gave a (2-bromoethyl)phosphate ester, which on quaternization with aqueous trimethylamine afforded 3-deoxy-N-palmitoyl-(R)-sphingomyelin (2) in 49percent overall yield from PMP (S)-2-hydroxy-4-octadecynyl ether (7).