A P-hydroxy

As a p hydroxy derivative of phenylalanine tyrosine has properties similar to those of phenylalanine plus the ability to engage m hydrogen bonding via its —OH group Asparagine and glutamine are not amines they are amides The side chains of both O... 

A/-(P-hydroxy)ethyl- aceto acetamide [24309-97-5] mp 35—40 animal feed additive... 

Step 2 The alkoxide ion abstracts a proton from water to give the product of aldol addition, a p-hydroxy aldehyde. ... 

The product is a P-hydroxy aldehyde (called an aldol) or ketone, which in some cases is dehydrated during the course of the reaction. Even if the dehydration is not spontaneous, it can usually be done easily, since the new double bond is in conjugation with the C=0 bond so that this is a method of preparing a,P-unsaturated aldehydes and ketones as well as P-hydroxy aldehydes and ketones. The entire reaction is an equilibrium (including the dehydration step), and a,P-unsaturated and P-hydroxy aldehydes and ketones can be cleaved by treatment with OH (the retrograde aldol reaction). There is evidence that an SET mechanism can intervene when the substrate is an aromatic ketone. ... 

In the presence of a strong base, the ot carbon of a carboxylic ester can condense with the carbonyl carbon of an aldehyde or ketone to give a P-hydroxy ester, which may or may not be dehydrated to the a,P-unsaturated ester. This reaction is sometimes called the Claisen reaction,an unfortunate usage since that name is more firmly connected to 10-118. In a modem example of how the reaction is used, addition of tert-butyl acetate to LDA in hexane at -78°C gives the lithium salt of ferf-butyl acetate, " (12-21) an enolate anion. Subsequent reaction a ketone provides a simple rapid alternative to the Reformatsky reaction (16-31) as a means of preparing P-hydroxy erf-butyl esters. It is also possible for the a carbon of an aldehyde or ketone to add to the carbonyl carbon of a carboxylic ester, but this is a different reaction (10-119) involving nucleophilic substitution and not addition to a C=0 bond. It can, however, be a side reaction if the aldehyde or ketone has an a hydrogen. 

Ij ample Compound (21) is a P-hydroxy ketone. Disconnect ion of the usual bond reveals two molecules of onone (22), disconnected in turn to two molecules of acetone,... 

Finally, Mikami and Motoyama have used a p-hydroxy sulfonamide ligand to catalyse the enantioselective B-catalysed Diels-Alder reaction of glyoxylate with Danishefsky s dienes." " A favourable transition-state assembly for a one-directional diene-approach from the site proximal to the sulfonylamino moiety was proposed to explain the observed high enantio- and c (e fi o)-diastereos-electivity (Scheme 5.28). 

Detailed investigations of the chemical reactivity of the diketiminato-stabilized phosphenium cations like 28 (Scheme 17) are to date rare and include only two reports dealing with the substitution and reduction of P-halogen-derivatives. Thus, reaction of 28 (X=Br) with sodium hydroxide in toluene was reported to proceed with displacement of the halide substituent at phosphorus and conservation of the heterocyclic ring to give a mixture of bromide and triflate salts containing a P-hydroxy-substituted cation, both of which were isolated in small yields [89], The products are remarkable as they represent one of very few examples of a stable phosphinous acid which does not rearrange to the tautomeric secondary phosphine oxide. Potassium reduction of the P-chloro-substituted derivative 34 produced the... 

Evidence for this consideration lies in the fact that the basic structure of methyl-p-methoxycinnamate is analogous to that of a p-hydroxy-phenylpropane unit from which p-hydroxybenzaldehyde could arise upon oxidation. This consideration supports and amplifies the experimental findings embodied in the phase sequence devised previously (79). 

Oxidative desulfonylation polyenes. Oxidation of the anion of a primary sulfone with MoOPH results in a p-hydroxy sulfone formed by condensation of... 

Other classes of alcohols are unreactive. Ethyl 3-hydroxybutyrate (a p-hydroxy ester) went to the phosphate stage, but would not undergo azide displacement. In this example about 30% of the crotonate was formed because of p-elimination. 

Cleavage of the isoxazolidine ring can also be effected directly to give similar products as the isoxazoline. Upon the addition of methoxide to an isoxazolidine bearing a hydrogen at C(3), fragmentation reveals a p-hydroxy oxime, which can be further hydrolyzed to the corresponding ketone (16,20,34,108). The P-hydroxy... 

Conversion of the hydroxyl group of a p-hydroxy amide to a mesylate, triilate, ° ° or an acetate ° ° followed by intramolecular displacement of the leaving group is a commonly employed strategy for oxazoline formation. Some examples from the recent literature are hsted in Table Oxazolines... 

The reaction therefore constitutes a method for converting an organometallic compound R M to an aldehyde R CHO (see also 2-32), an oi-keto acid,809 a ketone R COR (see also 2-32), an a-hydroxy ketone, or a p-hydroxy ketone. In each case the C=N bond is hydrolyzed to a 0=0 bond (6-2). 

COSY spectrum of a p-hydroxy ketone derivative C in DMSO-dg... 

The key step of the approach to 45 is the ring opening of /V-Boc p-lactam 43 with ammonia, Scheme 17. The synthesis starts from the 4-carboxy azetidin-2-one 41, which is a p-hydroxy aspartic acid form possessing the p-carboxyl group and the a-amino moiety simultaneously protected. The dipeptide unit 42 is obtained in 95% overall yield after activation of the a-carboxy group with cyanuric fluoride and... 

The product of this conjugate addition is a p-hydroxy ketone. It undergoes base-catalyzed cleavage to the observed products. 

Hymenocardine (58), (32, 40) has a p-hydroxy-w-aminoacetophenone unit (81), instead of the usual styrylamine, in its cyclic system which can be recognized in addition to N,N-dimethylisoleucylvaline and tryptophan in its acid hydrolysate. Mild alkaline hydrolysis results in ring opening via /3 elimination on the hydroxyamino acid and severance of the phenolate to a tetrapeptide 82 whose structure was determined by mass spectrometry and further hydrolysis. It is the only peptide alkaloid in which /3-hydroxy valine is involved in the aryl ether bridge. 

Like the related fatty acid synthases (FASs), polyketide synthases (PKSs) are multifunctional enzymes that catalyze the decarboxylative (Claisen) condensation of simple carboxylic acids, activated as their coenzyme A (CoA) thioesters. While FASs typically use acetyl-CoA as the starter unit and malonyl-CoA as the extender unit, PKSs often employ acetyl- or propionyl-CoA to initiate biosynthesis, and malonyl-, methylmalonyl-, and occasionally ethylmalonyl-CoA or pro-pylmalonyl-CoA as a source of chain-extension units. After each condensation, FASs catalyze the full reduction of the P-ketothioester to a methylene by way of ketoreduction, dehydration, and enoyl reduction (Fig. 3). In contrast, PKSs shortcut the FAS pathway in one of two ways (Fig. 4). The aromatic PKSs (Fig. 4a) leave the P-keto groups substantially intact to produce aromatic products, while the modular PKSs (Fig. 4b) catalyze a variable extent of reduction to yield the so-called complex polyketides. In the latter case, reduction may not occur, or there may be formation of a P-hydroxy, double-bond, or fully saturated methylene additionally, the outcome may vary between different cycles of chain extension (Fig. 4b). This inherent variability in keto reduction, the greater variety of... 

Polyols. Rychnovsky4 has used the BF3-catalyzed coupling of oxiranes with an alkyllithium of Ganem (12, 68) to obtain polyol chains. Thus the tetraalkyltin 1 reagent prepared from a P-hydroxy aldehyde reacts with the oxirane 2 in the presence of BF3 etherate (2.5 equiv.) to give the protected decanehexol 3. 

Alkene synthesis.9 The key step in the Julia synthesis of alkenes (11, 473-475) involves reductive elimination of a P-hydroxy sulfone with sodium amalgam. A recent modification involves elimination of a p-hydroxy imidazolyl sulfone with Sml2 (equation I).1 Both syntheses are particularly useful for preparation of disubstituted alkenes and conjugated dienes and trienes. Both methods of elimination favor formation of (E)-alkenes. In a direct comparison, a higher yield was obtained with Sml2 than with Na(Hg). 

Chemical Name 3,5-Dihydroxy-a-[[(p-hydroxy-a-methylphenethyl)amino] methyl]benzyl alcohol hydrobromide... 

Aldol condensation of the zinc enolate of resin-bound alkyl ester 29 with aromatic aldehyde or ketone forms a P-hydroxy ester, which upon treatment with DIBAL-H leads to simultaneous reduction and cleavage of the ester moiety from the resin to give a soluble 1,3-diol 31 [31], Parallel synthesis utilizing three ester and nine carbonyl building blocks afforded a library of 27 analogs which was screened for antioxidative efficiency using a ferric thiocyanate assay. 

Dropwise addition of a P-hydroxy ester THF solution to a THF solution of MeZnBr (1 equiv.) at 0°C. 

When you need to synthesize a p-hydroxy ketone or aldehyde or an a,p-unsaturated ketone or aldehyde, use an aldol reaction. When you need to synthesize a p-diketone or p-keto ester, use a Claisen reaction. When you need to synthesize a 1,5-dicarbonyl compound, use a Michael reaction. The Robinson annulation is used to synthesize polycyclic molecules by a combination of a Michael reaction with an aldol condensation. 

Aldol condensation reaction (Section 23.1) the nucleophilic addition of an enol or enolate ion to a ketone or aldehyde, yielding a p-hydroxy ketone. 

Lewis acids can also be used to effect deacetalisation under mild conditions. A stringent example comes from a synthesis of Milbemycin by Ley and co-workers [Scheme 2,8),25 in which deacetalisation released a P-hydroxy ketone that was prone to elimination. However, by simply treating the acetal with PdCl2(MeCN)2 in acetone26 at room temperature, the requisite product was obtained in 94% yield. Under these conditions, acetals can be released in the presence of tertiary alcohols or oxiranes without incident [Scheme 2,9].27,28... 

Reaction of a p-hydroxy ketone with chloro-di-isopropylsilane provides a [3-hy-drosilyloxy ketone that delivers hydride to the ketone function in the presence of tin (IV) chloride. Hie reaction provides a highly diastereoselective method for preparing 1,3-diols via intramolecular hydrosilylation [Scheme 3.121].227... 

The enoyl-CoAis then a substrate for the addition of water across the carbon-carbon double bond. This results in a p-hydroxy-acyl-CoA compound, because the OH of water is added to the carbon further away from the carboxyl group ... 

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