Activism, anti-alcohol

To challenge attitudes to anti-social or criminal activities, and alcohol or drug use. 

The complex -Tol-BINAP-AgF (/>-Tol-BINAP - 2,2 -bis(di-/)-tolylphosphanyl)-l,l -binapthyl) catalyzes the asymmetric addition of allylic trimethoxysilanes to aldehydes (Equation (7)).7 3 The process can provide various optically active homoallylic alcohols with high enantioselectivity (up to 96% ee) and a remarkable 7 and anti- selectivities are observed for the reaction with crotylsilanes, irrespective of the configuration of the double bond ... 

Reactions of aldehydes with complexes 13—17 provide optically active homoallylic alcohols. The enantioselectivities proved to be modest for 13—16 (20—45% ee). In contrast, they are very high (> 94% ee) for the (ansa-bis(indenyl))(r]3-allyl)titanium complex 17 [32], irrespective of the aldehyde structure, but only for the major anti diastereomers, the syn diastereomers exhibiting a lower level of ee (13—46% ee). Complex 17 also gives high chiral induction (> 94% ee) in the reaction with C02 [32], in contrast to complex 12 (R = Me 11 % ee R = H 19% ee) [15]. Although the aforementioned studies of enan-... 

In 1993, Hayashi and co-workers reported a catalytic asymmetric synthesis of alle-nylboranes 256 by palladium-catalyzed hydroboration of conjugated enynes 253 (Scheme 4.66) [105]. Reaction of but-l-en-3-ynes 253 with catecholborane 254 in the presence of a catalyst, prepared from Pd2(dba)3 CHC13 (1 mol%) and a chiral mono-dentate phosphine ligand (S)-MeO-MOP 255 (1 mol%), gave an allenylborane 256. The ee of 256 was determined by the reaction with benzaldehyde affording the corresponding optically active homopropargyl alcohols 257 with up to 61% ee (syn anti= 1 1—3 1). 

Asymmetric synthesis of stavudine and cordycepin, anti-HIV agents, and several 3 -amino-3 -deoxy-P-nudeosides was achieved utilizing this cycloisomerization of 3-butynols to dihydrofuran derivatives [16]. For example, Mo(CO)6-TMNO-promoted cyclization of the optically active alkynyl alcohol 42, prepared utilizing Sharpless asymmetric epoxidation, afforded dihydrofuran 43 in good yield. Iodine-mediated introduction of a thymine moiety followed by dehydroiodination and hydrolysis of the pivaloate gave stavudine in only six steps starting from allyl alcohol (Scheme 5.13). 

Barbas and colleagues have applied the organocatalytic direct amination of aldehydes in a series of reports [7]. By combining acetone, various aldehydes, dibenzyl azodicarboxylate and i-proline as the catalyst, a one-pot synthesis of functionalized /Tamino alcohols was achieved [7a]. The scope of the reaction was found to be quite general for various aldehydes, and the optically active / -amino alcohols were obtained in high yields with low diastereoselective control. However, excellent enantioselectivity of especially the anti-adduct was obtained. 

Digestion yields the active anti-PTH aglycone Coniferyl alcohol [lignin synthesis precursor]... 

Chiral all-syn-l,3-polyols.ls A reiterative route to these polyols from an optically active epoxide (1) involves ring opening with a cuprate derived from vinyllithium and copper cyanide (11, 366-367) to give an optically active homoallylic alcohol (2). This is converted into the epoxide (4) via a cyclic iodocarbonate (3) by a known procedure (11, 263). Repetition of the cuprate cleavage results in a homoallylic 1,3-diol (5). The ratio of desired syn- to anti-diols is 10-15 1. This two-step sequence can be repeated, with each 1,3-diol unit formed being protected as the acetonide. The strategy is outlined in Scheme (I). 

In the oxidation of a diastereomeric mixture of carveol (syrr.anti = 42 58), the syn alcohol is stereoselectively oxidized and the anti alcohol is recovered in 98 % diastereomeric purity. This shows that the catalytic activity of (C6p5)2BOH is very sensitive to steric hindrance in the alcohols (Eq. 108). In oxidations of equimolar mixtures of geraniol and j8-citronellol, geranial is obtained in 96 % yield and most of the /8-citro-nellol is recovered imchanged (Eq. 109). The selective conversion of allylic alcohols in the presence of saturated alcohols is particularly noteworthy. 

C(3)-substituted allylsilanes (crotylsilanes) participate in chelation-controlled addition reactions with aldehydes to give syn addition products as the major stereoisomers. Generally, the ( )-crotylsilanes are highly selective in the syn sense (>9S 5). In contrast, the (Z)-crotylsilanes are much less selective (60-70 40-30 syn anti Scheme 42). Hayashi and Kumada have report a successful approach to optically active homoallyl alcohols using this strategy. They have reported that useful levels of asymmetric... 

The remaining segment, C-3 to C-8, was constructed by a similar route. Optically active allylic alcohol 229, produced from lithio ethylacetate and methacrolein followed by a second Sharpless kinetic resolution, was hydrolized to the corresponding hydroxy acid. Neutralization followed by iodolactonization then gave 230 in 85% yield. This highly stereoselective cyclization produced a cis-trans ratio of 20 1 via a one-pot procedure. Deprotonation and methylation afforded the expected anti a-methyl compound, contaminated with about 10% of the syn compound but none of the methyl ether. Formation of the silyl ether then produced 231 in 66% yield. Dibal reduction to the aldehyde concomitant... 

CS-670 is a racemic NSAID which is readily metabolized to active metabolites trans and unsaturated mono-ols. When cw-OH is administered to rats, approximately 9% of the trans diols were excreted in urine. However, the production of c -diols from trans-OH was only 0.51% of the dose. The chiral inversion from c -OH to trans-OH has been suggested to occur through the saturated ketone intermediate [63,133] (Fig. 9). Nevertheless, as the trans and the unsaturated alcohol (Fig. 9) are active anti-inflammatory analgesics and the ds alcohol has immuonomodulating activity, it is very important to evaluate the disposition of each enantiomer in order to understand pharmacological and toxicological properties of CS-670 [62,133]. 

Bacher et al. reported the synthesis of a potentially active anti-inflammatory steroid, 16o -carbomethoxyprednisolone 225, via bromonitrile oxide (221) cycloaddition to steroidal enones 220a,b (Scheme 53) [ 155]. The bromo-isoxazoline 222b was subjected to reductive cleavage and the resulting nitrile 223 was hydrolyzed and esterified to afford 225. Although direct displacement of bromide in 222 by methoxide was not feasible, the authors succeeded in the above transformation via protection/deprotection of the primary alcohol. However, all attempts to transform methoxyisoxazoline 224 to the ester 225 via reductive cleavage of the N-0 bond proved futile. 

Chen, D., Cui, Q.C., Yang, H., Dou, Q.P. (2006) Disulflram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cnl-tures and xenografts via inhibition of the proteasome activity. Cancer Research, 66,10425-10433. 

Vetrichelvan, T, Jegadeesan, M., Devi, B.A. Anti-diabetic activity of alcoholic extract of Celosia argentea LINN. Seeds in rats. Bio. Pharm. Bull. 25(4), 526-528 (2002)... 

The stereochemistry of base-induced alkyl migration from boron to carbon in y-acetylvinylboranes (36) has been studied and migration shown to occur predominantly in an anti fashion with respect to the leaving group, as in (37), to produce a trans-sAlylic alcohol on oxidation (Scheme 13). The availability of optically active propargylic alcohols (see refs. 36, 37 2, 116 4, 142) as precursors for (36) means that the overall sequence accomplishes alkylation and enantioselective [l,3]-hydroxyl transposition enantiomer ratios up to 87 13 were achieved in the alcohol product. 

A-Alkylation of amides and amines and dehydrative -alkylation of secondary alcohols and a-alkylation of methyl ketones " have been carried out by an activation of alcohols by aerobic oxidation to aldehydes, with copper(II) acetate as the only catalyst. A relay race process rather than the conventional borrowing hydrogen-type mechanisms has been proposed for the aerobic C-alkylation reactions, based on results of mechanistic studies. A Winterfeldt oxidation of substituted 1,2,3,4-tetrahydro-y-carboline derivatives provides a convenient and efiflcient method for the synthesis of the corresponding dihydropyrrolo[3,2-fc]quinolone derivatives in moderate to excellent yields. The generality and substrate scope of this aerobic oxidation have been explored and a possible reaction mechanism has been proposed. Direct oxidative synthesis of amides from acetylenes and secondary amines by using oxygen as an oxidant has been developed in which l,8-diazabicyclo[5.4.0]undec-7-ene was used as the key additive and copper(I) bromide as the catalyst. It has been postulated that initially formed copper(I) acetylide plays an important role in the oxidative process. Furthermore, it has been postulated that an ct-aminovinylcopper(I) complex, the anti-Markovnikov hydroamination product of copper acetylide, is involved in the reported reaction system. Copper(I) bromide... 

A iD-Corticoids have been important intermediates since it was shown ° that substitution at C-9 enhances anti-inflammatory activity. These olefins are usually obtained from 11a- or 11)5-alcohols, and consequently several refined methods have been devised for effecting this dehydration. It is desirable that such methods be compatible with the presence of A" -3-ketone and 17-hydroxy functions. The first direct procedure for which high yields were claimed was described in a patent issued to Upjohn. According to this method, the alcohol (11a or )5) is treated first with A-bromoacetamide in pyridine, then with sulfur dioxide. Recently it has been claimed " that the A-haloamide/sulfur dioxide method gives results superior to other methods, although the methanesulfonyl chloride/sulfur dioxide procedure (see below) apparently was not compared (see also ref. 94). 

Since the addition of dialkylzinc reagents to aldehydes can be performed enantioselectively in the presence of a chiral amino alcohol catalyst, such as (-)-(1S,2/ )-Ar,A -dibutylnorephedrine (see Section 1.3.1.7.1.), this reaction is suitable for the kinetic resolution of racemic aldehydes127 and/or the enantioselective synthesis of optically active alcohols with two stereogenic centers starting from racemic aldehydes128 129. Thus, addition of diethylzinc to racemic 2-phenylpropanal in the presence of (-)-(lS,2/ )-Ar,W-dibutylnorephedrine gave a 75 25 mixture of the diastereomeric alcohols syn-4 and anti-4 with 65% ee and 93% ee, respectively, and 60% total yield. In the case of the syn-diastereomer, the (2.S, 3S)-enantiomer predominated, whereas with the twtf-diastereomer, the (2f ,3S)-enantiomer was formed preferentially. 

One limitation of these noncatalyzed allyl(trialkyl)- and allyl(triaryl)stannane-aldehyde reactions is the high temperature required unless the aldehyde is activated towards nucleophilic attack. Allyltin halides are much more reactive because of their enhanced Lewis acid character however 2-butenyltin halides show reduced syn I anti selectivity45, and give other products including linear homoallylic alcohols and tetrahydropyrans47. 

Apart from ethanol, other primary alcohols catalyse the formation of the dichloro complex, probably via a rhodium(I) intermediate rather than a rhodium(III) hydride. Rhpy4X2" compounds have anti-bacterial activity. 

It has also been shown that dimethylsilyl enolates can be activated by diisopropylamine and water and exhibit a high reactivity toward iV-tosyl imines to give Mannich-type reaction products in the absence of a Fewis acid or a Bronsted acid.51 For example, the reaction of [(1-cyclohexen-l-yl)oxy]dimethylsilane with 4-methyl-A -(phenylmethylene)benzene sulfonamide gave re/-4-methyl-N- (f )-[(15)-(2-oxocyclohexyl)phenyl-methyl] benzenesulfonamide (anti-isomer) in 91% yield stereoselectively (99 1 anti syn) (Eq. 11.30). On the other hand, Fi and co-workers reported a ruthenium-catalyzed tandem olefin migration/aldol and Mannich-type reactions by reacting allyl alcohol and imine in protic solvents.52... 

Two interesting yeast carbonyl reductases, one from Candida magnoliae (CMCR) [33,54] and the other from Sporobolomyces salmonicolor (SSCR) [55], were found to catalyze the reduction of ethyl 4-chloro-3-oxobutanoate to give ethyl (5)-4-chloro-3-hydroxybutanoate, a useful chiral building block. In an effort to search for carbonyl reductases with anti-Prelog enantioselectivity, the activity and enantioselectivity of CMCR and SSCR have been evaluated toward the reduction of various ketones, including a- and /3-ketoesters, and their application potential in the synthesis of pharmaceutically important chiral alcohol intermediates have been explored [56-58]. 

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