- COMPOUNDS AND METHODS FOR TARGETED DEGRADATION OF KRAS
-
Bifunctional compounds, which find utility as modulators of Kirsten ras sarcoma protein (KRas or KRAS), are described herein. In particular, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the Von Hippel-Lindau E3 ubiquitin ligase and on the other end a moiety which binds KRas, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The heterobifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
- -
-
Paragraph 00235
(2021/10/15)
-
- Catalyst-Free Decarbonylative Trifluoromethylthiolation Enabled by Electron Donor-Acceptor Complex Photoactivation
-
A catalyst- and additive-free decarbonylative trifluoromethylthiolation of aldehyde feedstocks has been developed. This operationally simple, scalable, and open-to-air transformation is driven by the selective photoexcitation of electron donor-acceptor (EDA) complexes, stemming from the association of 1,4-dihydropyridines (donor) with N-(trifluoromethylthio)phthalimide (acceptor), to trigger intermolecular single-electron transfer events under ambient- and visible light-promoted conditions. Extension to other electron acceptors enables the synthesis of thiocyanates and thioesters, as well as the difunctionalization of [1.1.1]propellane. The mechanistic intricacies of this photochemical paradigm are elucidated through a combination of experimental efforts and high-level quantum mechanical calculations [dispersion-corrected (U)DFT, DLPNO-CCSD(T), and TD-DFT]. This comprehensive study highlights the necessity for EDA complexation for efficient alkyl radical generation. Computation of subsequent ground state pathways reveals that SH2 addition of the alkyl radical to the intermediate radical EDA complex is extremely exergonic and results in a charge transfer event from the dihydropyridine donor to the N-(trifluoromethylthio)phthalimide acceptor of the EDA complex. Experimental and computational results further suggest that product formation also occurs via SH2 reaction of alkyl radicals with 1,2-bis(trifluoromethyl)disulfane, generated in-situ through combination of thiyl radicals. (Figure presented.).
- Lipp, Alexander,Badir, Shorouk O.,Dykstra, Ryan,Gutierrez, Osvaldo,Molander, Gary A.
-
supporting information
p. 3507 - 3520
(2021/06/11)
-
- MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE
-
The present disclosure relates to bifunctional compounds, which find utility as modulators of Kirsten rat sarcoma protein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation, accumulation, and/or overactivation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
- -
-
Paragraph 00763-00764
(2019/10/29)
-
- Posaconazole impurities and preparation method and use thereof
-
The invention discloses Posaconazole impurities, for example 4c shown in the description (PG is a hydroxyl protective group). Meanwhile, the invention further discloses a preparation method and use ofthe impurities.
- -
-
Paragraph 0164-0166
(2018/09/08)
-
- Stereoselective synthesis of C19-C27 fragment of bryostatin 11
-
A convergent synthesis of C19-C27 fragment (2) of bryostatin-11 is described. The key steps involved in this approach are kinetic resolution, Grignard reaction, and Sharpless dihydroxylation. AIBN catalyzed radical cyclization strategy has been used for the first time to construct the six-membered pyran system.
- Yadav,Swamy,Subba Reddy,Ravinder
-
p. 4054 - 4056
(2014/07/22)
-
- Stereoselective synthesis of C19-C27 fragment of bryostatin 11
-
A convergent synthesis of C19-C27 fragment (2) of bryostatin-11 is described. The key steps involved in this approach are kinetic resolution, Grignard reaction, and Sharpless dihydroxylation. AIBN catalyzed radical cyclization strategy has been used for the first time to construct the six-membered pyran system.
- Yadav,Swamy,Subba Reddy,Ravinder
-
p. 4054 - 4056
(2015/02/02)
-
- Synthetic approaches to the bottom half fragment for bryostatin 11
-
An approach towards the stereoselective synthesis of the bottom half fragment of bryostatin 11 is described. Key steps -include asymmetric aldol and Saksena-Evans reduction reactions -to construct multiple stereogenic centers and thioketalization-lactoniz
- Nakagawa-Goto, Kyoko,Crimmins, Michael T.
-
p. 1555 - 1558
(2011/08/05)
-
- Stereoselective direct amine-catalyzed decarboxylative aldol addition
-
A stereoselective decarboxylative aldol addition of β- and α-keto acids in the presence of catalytic amounts of amines is described. By the optional deployment of chiral enolizable aldehydes an access to enantiopure configurative defined ketopentoses, ketohexoses, or ketoheptoses is given.
- Rohr, Kerstin,Mahrwald, Rainer
-
supporting information; experimental part
p. 1878 - 1880
(2011/06/20)
-
- Highly diastereoselective α-hydroxylation of fox chiral auxiliary-based amide enolates with molecular oxygen
-
"Figure Presented" Using a trifluoromethylated oxazolidine (Fox) chiral auxiliary, the hydroxylation reaction of enolates was very efficiently performed under smooth and friendly conditions with molecular oxygen as oxidizer. This reaction occurred with an extremely high diastereoselectivlty. After cleavage, the chlral auxiliary Is efficiently recovered and highly valuable enantlopure oxygenated carboxylic acids and alcohols are released.
- Lubin, Hodney,Tessier, Arnaud,Chaume, Gregory,Pytkowicz, Julien,Brigaud, Thierry B.
-
supporting information; experimental part
p. 1496 - 1499
(2010/07/03)
-
- A concise asymmetric synthesis of (-)-hongconin and (-)-1-epi-hongconin
-
A concise asymmetric synthesis of (-)-hongconin and (-)-1epi-hongconin is described. The synthesis features an efficient combination of Doetz benzannulation or lactaldehyde arylation and the oxa-Pictet-Spengler reaction as the key steps. The synthesis is
- Fernandes, Rodney A.,Chavan, Vijay P.
-
experimental part
p. 4306 - 4311
(2010/10/19)
-
- Alkylation and aldol reactions of acyl derivatives of N-1-(1′-naphthyl)ethyl-O-tert-butylhydroxylamine: asymmetric synthesis of α-alkoxy-, α-substituted-β-alkoxy- and α,β-dialkoxyaldehydes
-
Treatment of a range of O-protected glycolate derivatives of the chiral auxiliary N-1-(1′-naphthyl)ethyl-O-tert-butylhydroxylamine with KHMDS in the presence of 18-crown-6 followed by addition of an alkyl halide generates α-substituted derivatives with very high levels of diastereoselectivity. Alternatively, reaction of the potassium enolate of a propanoate or O-protected glycolate derivative of N-1-(1′-naphthyl)ethyl-O-tert-butylhydroxylamine with a range of aldehydes gives syn-aldol products with high levels of diastereoselectivity. These adducts may be reductively cleaved with LiAlH4 to give enantiopure α-alkoxy-, α-substituted-β-alkoxy- and α,β-dialkoxyaldehydes in good yield.
- Chernega, Alexander N.,Davies, Stephen G.,Fletcher, Ai M.,Goodwin, Christopher J.,Hepworth, David,Prasad, R. Shyam,Roberts, Paul M.,Savory, Edward D.,Smith, Andrew D.,Thomson, James E.
-
experimental part
p. 4167 - 4194
(2010/07/06)
-
- BRYOSTATIN ANALOGUES, SYNTHETIC METHODS AND USES
-
Biologically active compounds related to the bryostatin family of compounds, having simplified spacer domains and/or improved recognition domains are disclosed, including methods of preparing and utilizing the same.
- -
-
Page/Page column 79
(2009/05/28)
-
- BRYOSTATIN ANALOGUES, SYNTHETIC METHODS AND USES
-
Biologically active compounds related to the bryostatin family of compounds, including methods of utilizing the same.
- -
-
Page/Page column 57
(2009/10/31)
-
- A stereoselective approach for the total synthesis of clonostachydiol
-
A stereoselective synthesis of clonostachydiol is accomplished using readily available (±)-epichlorohydrin as a precursor. The synthesis involves direct and straightforward reactions such as Sharpless asymmetric epoxidation, iodination, stereoselective op
- Yadav,Swamy,Subba Reddy
-
scheme or table
p. 2773 - 2776
(2009/04/16)
-
- Concise formal synthesis of the bryostatin southern hemisphere (C17-C27)
-
An efficient synthesis of Hale and co-workers' C17-C27 bryostatin southern hemisphere intermediate has been accomplished in six steps and 33% overall yield from (R)-2-(benzyloxy)propanal. The synthesis features a one-pot DIBALH/HWE ester homologation as w
- Voight, Eric A.,Roethle, Paul A.,Burke, Steven D.
-
p. 4534 - 4537
(2007/10/03)
-
- Stereoselective synthesis of functionalised triol units by SnCl4 promoted allylation of α-benzyloxyaldehydes: Crucial role of the stoichiometry of the Lewis acid
-
Enantiomerically pure syn-anti and syn-syn configured triol units are efficiently synthesized by the SnCl4 mediated allylation of chiral α-benzyloxyaldehydes with the uniquely functionalised allylstannane 9. Remarkably, the stereochemistry of t
- Dubost, Christophe,Leroy, Bernard,Markó, Istvan E.,Tinant, Bernard,Declercq, Jean-Paul,Bryans, Justin
-
p. 7693 - 7704
(2007/10/03)
-
- Total synthesis of motuporin (nodularin-v)
-
The serine/threonine phosphatase (protein phosphatase 1 and 2A) inhibitors constitute a biologically and structurally interesting class of natural products. Among this class of inhibitors are cyclic pentapeptides (nodularins) and cyclic heptapeptides (mic
- Bauer, Shawn M.,Armstrong, Robert W.
-
p. 6355 - 6366
(2007/10/03)
-
- Hydroxynitrile lyase catalyzed enantioselective HCN addition to O-protected α-hydroxyaldehydes
-
Various O-protected glycol- and racemic lactaldehydes 3 and 6 as well as O-allyl protected racemic α-hydroxyaldehydes 7 (R1=Et, Pr, Bu) have been prepared to investigate and perform a stereoselective Kiliani-Fischer synthesis by hydroxynitrile lyase (HNL) catalyzed addition of HCN. From all protecting groups investigated the allyl moiety was most suitable. (R)-PaHNL from bitter almonds (Prunus amygdalus), yielding the (2S)-cyanohydrins 8-10, was found to be a more stereoselective catalyst than (S)-MeHNL from maniok (Manihot esculenta). While (R)-PaHNL led to enantiomeric excesses ≥93%, with (S)-MeHNL the (2R)-cyanohydrins 8-10 were obtained with enantiomeric excesses ≤78%.
- Roos, Juergen,Effenberger, Franz
-
p. 2817 - 2828
(2007/10/03)
-
- Almond oxynitrilase-catalyzed transformation of aldehydes is strongly influenced by naphthyl and alkoxy substituents
-
Different α- and β-substituted aldehydes have been submitted to the catalytic action of almond oxynitrilase (PaHNL), in order to explore the influence of a stereocenter already present in the substrate on the selectivity of this enzyme. The results indicate that naphthyl and alkoxy substituents in the α- and also in the β-position to the aldehyde group significantly influence the stereochemical outcome of the PaHNL-catalyzed transformation.
- Roda, Gabriella,Riva, Sergio,Danieli, Bruno
-
p. 3939 - 3949
(2007/10/03)
-
- Enantioselective synthesis of (+)-(2R,3S,6R)-decarestrictine L
-
A convergent enantioselective synthesis of (+)-(2R,3S,6R)- decarestrictine L (1), a natural inhibitor of cholesterol biosynthesis, is described from commercially available (S)-malic acid and (R)-isobutyl lactate. The third chiral center was created by stereoselective reduction of a chiral α-hydroxy ketone, and an intramolecular S(N)2-type reaction allowed the stereocontrolled formation of the tetrahydropyranyl ring.
- Solladie, Guy,Arce, Eva,Bauder, Claude,Carmen Carreno
-
p. 2332 - 2337
(2007/10/03)
-
- Stereoselective Reactions of Phthalimido-Substituted Radicals Derived from (±)-Threonine: A Comparison with Reactions of N-Phthaloyliminium Ions
-
Stereoselective reactions of phthalimido-substituted radicals derived from (±)-threonine with different radical traps are reported (Scheme 3, Table 1). A strong influence of the nature of the radical trap on the stereoselectivity was noticed. Small nucleophilic radical traps gave preferentially the syn products. The observed selectivities are explained with the A1.3 strain model and depend on steric and electronic effects (Fig. 2). Reactions with electrophilic radical traps such as diphenyl diselenide gave the anti diastereoisomers with moderate stereocontrol, presumably due to stereoelectronic effects. The same stereochemical outcome, i.e., preferential formation of the anti products, was observed for the reactions of the related N-phthaloyliminium ion (Scheme 5, Table 2). The stereochemistry of the ionic reaction is rationalized by a Felkin-Anh model (Fig. 3).
- Stojanovic, Aleksandar,Renaud, Philippe,Schenk, Kurt
-
p. 268 - 284
(2007/10/03)
-
- Z-selective Horner-Wadsworth-Emmons reaction of (α-substituted ethyl (Diarylphosphono)acetates with aldehydes
-
New Horner-Wadsworth-Emmons reagents, ethyl 2- (diarylphosphono)propionates (2), ethyl 2-(diarylphosphono)hexanoates (3), and ethyl 2-(diarylphosphono)-3-methylbutanoates (4) were prepared by alkylation of ethyl (diarylphosphono)acetates. The reaction of
- Ando, Kaori
-
p. 8411 - 8416
(2007/10/03)
-
- Preparation of (R)-(+)-Lithium Lactate
-
Optically pure (R)-(+)-lithium lactate (7) and its benzyl ether analogue (6a) were obtained from acetaldehyde using Eliel's 1,3-trans-oxathiane (1) as the chiral auxiliary for chromatographic separation.
- Cervantes-Cuevas,Joseph-Nathan
-
p. 201 - 206
(2007/10/03)
-
- Highly Selective Synthesis of Z-Unsaturated Esters by Using New Horner-Emmons Reagents, Ethyl (Diarylphosphono)acetates
-
New Horner-Emmons reagents, ethyl (diarylphosphono)acetates 1, were prepared from triethyl phosphonoacetate, PCl5 the corresponding phenols. The reaction of 1 with several kinds of aldehydes in the presence of Triton B or NaH in THF solvent revealed that these reagents are useful for the synthesis of Z-unsaturated esters. Among the reagents examined, ethyl(di-o-tolylphosphono)-, [bis(o-ethylphenyl)phosphonol-, and [bis(o-isopropylphenyl)phosphono]acetates (1k-m) were found to be the most effective, giving Z-unsaturated esters with 93-99% selectivity.
- Ando, Kaori
-
p. 1934 - 1939
(2007/10/03)
-
- Synthetic studies on the rhizoxins. II. An approach to the C10-C26 subunit using 'substrate directed' allylstannane additions to aldehydes
-
The construction of a C10-C26 fragment of the 16-membered antitumor macrolide rhizoxin has been achieved in an efficient manner. The central portion of this molecule has been prepared in enantiopure form via an iterative allylstannylation protocol starting with the ester of (R)-lactic acid. The oxazole portion of rhizoxin was attached via a samarium diiodide modified Julia coupling to generate the requisite all E triene.
- Keck,Savin,Weglarz,Cressman
-
p. 3291 - 3294
(2007/10/03)
-
- Diastereo- and enantioselective synthesis of 1,2-amino alcohols and protected α-hydroxy aldehydes from glycol aldehyde hydrazones
-
Starting from chiral glycol aldehyde hydrazones (S)-2, we prepared differently protected α-hydroxy aldehydes (R)- or (S)-4 as well as N-acetyl-protected 1,2-amino alcohols (R)-11 in high enantiomeric excesses via azaenolate α-alkylation or nucleophilic 1,2-addition to the CN double bond. The successive introduction of two vicinal stereogenic centres opens a new, flexible syn-diastereo- and enantioselective route to functionalised, N-acetyl-protected, vicinal amino alcohols (R,R)-13, which was demonstrated in the case of the γ-amino-β-hydroxycarboxylic acid statin (R,R)-15 and its analogues B. VCH Verlagsgesellschaft mbH, 1996.
- Enders, Dieter,Reinhold, Ulrich
-
-
- Steric and Electronic Effects in Conformational Preferences of C1-Oxygenated Chiral Alkenes
-
A variable temperature NMR study shows that the benzyl protective group on the hydroxy function of a chiral allylic alcohol enhances the CH eclipsed from (I).On the other hand, various silyl ethers enhance the preference for the CO eclipsed conformer.However, when both the allylic R group and the hydroxy protective group are bulky (R = tert-butyl, P = TIPS), the staggered conformation of the chiral alkene becomes preferred.An acetate group does not have an apparent effect on the conformational preference of the protected allylic alcohol.These facts are explained in terms of steric and electronic interactions.
- Gung, Benjamin W.,Melnick, Jason P.,Wolf, Mark A.,King, Amanda
-
p. 1947 - 1951
(2007/10/02)
-
- Total Synthesis of (-)-Grayanotoxin III
-
Total synthesis of (-)-grayanotoxin III (3), a unique tetracyclic diterpene isolated from the leaves of various plants of the family Ericaceae, has been successfully accomplished featuring the highly stereoselective cyclization reactions induced by SmI2.
- Kan, Toshiyuki,Hosokawa, Seijiro,Nara, Shinji,Oikawa, Masato,Ito, Shinya,et al.
-
p. 5532 - 5534
(2007/10/02)
-
- Stereoselective dioxygenation of enoates
-
The auxiliary-directed reaction of singlet oxygen with tiglate esters furnishes an asymmetric synthesis of 3-hydroperoxy-2-methylidene butenoates. Although previous reports have suggested that s-cis enoate conformers undergo preferential oxygenation relative to the s-trans conformers, our results suggest that both conformers are reactive and that the modest stereoselectivity is based upon a conformational equilibrium favoring the s-trans conformer.
- Dussault, Patrick H.,Woller, Kevin R.,Hillier, Michael C.
-
p. 8929 - 8940
(2007/10/02)
-
- Acyclic stereoselection in the tertiary amine-catalysed addition of activated vinyl systems (Baylis-Hillman reaction) to protected chiral α-hydroxy and α-amino aldehydes
-
The non chelation-controlled aldol-type addition of the ambident vinyl α anions derived from acrylic esters and methyl vinyl ketone to a series of protected chiral α-hydroxy and α-amino aldehydes has been investigated in order to assess some of the factors which contribute to the control of the diastereofacial selectivity.Whlist the α-methylene-β,γ-disubstituted carbonyl products showed a general preference for selectivity, some examples of syn predominance were made possible via a 'substituent tuning'approach.The observed diastereomer ratios have been interpreted in terms of the Felkin model and the Anh-Eisenstein proposals for 1,2-asymmetric induction.Simple steric effects appear to be as important as ?-orbital energies in the designation of the large 'anti group' for the application of these transition-state interpretations.Attempts to improve the overall induction via double diastereoselection approach, which combines the 1,5-induction of chiral acrylates with the 1,2-induction already present, were largely inconclusive.Methods for the routine NMR assignment of the relevant stereo-substructures have been assessed and the use of novel complementary technique is described.
- Manickum, Thavrin,Ross, Gregory H. P.
-
-
- Palladium-catalyzed hydrogenolysis of acyldimethylphenylsilanes to aldehydes
-
Syn-α,β-dialkoxy-acyldimethylphenylsilanes of structural type 1, bearing benzyl, benzyloxymethyl (BOM) ether protecting groups can be efficiently and selectively desilated to produce the corresponding aldehydes 2 by catalytic hydrogenolysis over 10% palla
- Cirillo, Pier F.,Panek, James J.
-
p. 457 - 460
(2007/10/02)
-
- Enantiomerically Pure 2-(Carbamoyloxy)oxiranes and Their Utility in the Synthesis od D- and L-3,6-Dideoxy-3-C-methylhexofuranosides via the Homoaldol Reaction
-
As an example of a novel flexible strategy in the rapid enantioselective construction of branched carbohydrate analogues by the homoaldol reaction, the title compounds were synthesized. α-Metalated (E)-2-butenyl N,N-diisopropylcarbamate is added to (S)- or (R)-2-benzyloxypropanal.The homoaldol adducts are epoxidized; methanolysis affords furanosides of branched 3,6-dideoxyaldohexoses, or, hydrolysis yields the furanoses.
- Hoppe, Dieter,Tarara, Gerhard,Wilckens, Marcus
-
-
- ENZYMATIC PREPARATION OF OPTICALLY ACTIVE α AND β-HYDROXYALDEHYDES
-
Resolution of protected α and β-hydroxyaldehydes 1a-e, chiral building blocks in the synthesis of natural products, was easily achieved by lipase-catalyzed stereoselective hydrolysis of corresponding acetic or butyric ester derivative.
- Bianchi, Daniele,Cesti, Pietro,Golini, Paolo
-
p. 869 - 876
(2007/10/02)
-
- STEREOSELECTIVE SYNTHESIS OF α-METHYLENE-β-HYDROXY-γ-ALKOXY ESTERS AND KETONES
-
The amine catalysed aldol-type addition of vinylcarbonyl units to α-alkoxy aldehydes proceeds with reasonable diastereoface selectivity to afford the title compounds in good yield.
- Drewes, Siegfried E.,Manickum, Thavrin,Roos, Gregory H. P.
-
p. 1065 - 1070
(2007/10/02)
-
- Synthesis of Analogues of 1,3-Dihydroxyacetone Phosphate and Glyceraldehyde 3-Phosphate for Use in Studies of Fructose-1,6-diphosphate Aldolase
-
This paper describes the synthesis of five analogues of dihydroxyacetone phosphate (3-azidohydroxyacetone 1-phosphate (5), 3-(acetylamino)hydroxyacetone 1-phosphate (12), (R)-1,3-dihydroxy-2-butanone 1-phosphate (18), (+/-)-1,3-dihydroxy-2-butanone 3-phosphate (26), and phosphonomethyl glycolate (31)).The syntheses of 18 and 26 are based on a new reaction: that is, the introduction of the phosphate group by the reaction of a diazo ketone with dibenzyl phosphate.These methods provide easy access to a number of compounds that are potential substrates for the synthetically useful enzyme aldolase (fructose-1,6-diphosphate aldolase from rabbit muscle, EC 4.1.2.13, RAMA) and perhaps for other enzymes of glycolysis.This paper also describes syntheses of 14 aldehydes for examination as substrates for aldolase.When the precursor was available, ozonolysis of vinyl groups proved to be the best route to the corresponding aldehydes.
- Bischofberger, Norbert,Waldmann, Herbert,Saito, Tohru,Simon, Ethan S.,Lees, Watson,et al.
-
p. 3457 - 3465
(2007/10/02)
-
- FACTORS AFFECTING REGIOSLECTIVITY IN THE RHODIUM-CATALYSED HYDROFORMYLATION OF VINYL ETHERS
-
The rhodium catalysed hydroformylation of vinyl ethers ROCH=CH2, where R is an alkyl, a benzyl or a phenyl group, has been investigated over the 20-100 deg C temperature range in the presence of Rh4(CO)12 or 2/PPh3 (1/6) as catalytic precursors.A mixture of 2-alkoxy-(or phenoxy)propanal (the α-isomer) and 3-alkoxy-(or phenoxy)propanal (the β-isomer) is obatined in good yield.The isomeric composition of the aldehydes depends on the structure of the substrate, on the catalytic precursor employed, and on the reaction temperature.The α-isomer predomines in all the cases, its predominance being greater (i) at low temperatures, (ii)in the presence of Rh4(CO)12 as catalyst precursor, and (iii) when a phenyl group is present in the β or γ position with respect to the double bond in the substrate.Electronic factors arising from the presence in the substrate of the oxygen atom and a phenyl group are more impotrant than the steric hindrance of tghe R group in detrmining the regioselectivity of the reaction.
- Lazzaroni, Raffaelo,Bertozzi, Sergio,Pocai, Paolo,Troiani, Francesco,Salvadori, Piero
-
p. 371 - 376
(2007/10/02)
-
- Synthesis of (S) and (R) O-Benzyl-lactaldehyde
-
(3S,4S) 3,4-Isopropylidendioxypentan-2-one (6) is reduced by metal hydrides to (2S,3R,4S) 3,4-isopropylidendioxypentan-2-ol (7) and to the (2R,3R,4S) isomer (9), subsequently converted into (S) and (R) O-benzyl-lactaldehyde (4) and (5); (S) and (R) O-benzyl-lactaldehyde (4) and (5); (S) O-benzyl-lactaldehyde (4) is also obtained in ca. 90percent ee from (2S) 4-phenylbut-3-en-2-ol (16), prepared by baker's yeast reduction of benzylideneacetone (15).
- Fuganti, Claudio,Grasselli, Piero,Servi, Stefano,Spreafico, Franca,Zirotti, Carlo
-
p. 976 - 984
(2007/10/02)
-
- 1-Aminoalkylphosphonous Acids. Part 1. Isosteres of the Protein Amino Acids
-
The synthesis of 1-aminoalkylphosphonous acids, isosteres of the protein amino acids, by addition of hypophosphorous acid to diphenylmethylimines is described.These analogues of glycine, alanine, valine, leucine, isoleucine, phenylalanine, tyrosine, tryptophan, serine, threonine, methionine, cysteine, cystine, glutamic acid, lysine, ornithine, arginine, and proline have been prepared and the analogues of alanine, valine, leucine, phenylalanine, and methionine resolved.The alanine, valine and methionine analogues have interesting antimicrobial activity and the alanine analogue has plant growth inhibiting properties.Oxidation of the appropriate 1-aminoalkylphosphonous acids gave the 1-aminoalkylphosphonic acid analogues of (+/-)-alanine, (-)-alanine, (+/-)-valine, (-)-valine, (+/-)-serine, (+/-)-threonine, (+/-)-lysine, (-)-leucine, and (+/-)-ornithine.
- Baylis, E. Keith,Campbell, Colin D.,Dingwall, John G.
-
p. 2845 - 2853
(2007/10/02)
-
- ON THE STERIC COURSE OF THE ADDITION OF SOME ORGANOMETALLIC REAGENTS TO (R)-2,3-ISOPROPYLIDENE GLYCERALDEHYDE. SYNTHESIS OF OPTICALLY ACTIVE α-BENZYLOXY ALDEHYDES, ALCOHOLS, CARBOXYLIC ACIDS AND 1,2-DIOLS.
-
Organo-titanium and organo-zinc reagents were added stereoselectively to (R)-2,3-isopropylidene glyceraldehyde (1) to give the alcohols 2/3, which were converted into the optically active derivatives 4-11.
- Mulzer, Johann,Angermann, Alfred
-
p. 2843 - 2846
(2007/10/02)
-
- Synthesis of Inhibitors of Adenosine Deaminase. A Total Synthesis of erythro-3-(Adenin-9-yl)-2-nonanol and Its Isomers from Chiral Precursors
-
The synthesis of both isomers of EHNA2 ("erythrohydroxynonyladenine") from D- and L-rhamnose is described.The key intermediates, (R)- and (S)-2-(benzyloxy)propanal, derived respectively from 5-O-benzyl-D- and -L-rhamnitol, were each condensed w
- Baker, David C.,Hawkins, L. D.
-
p. 2179 - 2184
(2007/10/02)
-
- Acyclic Stereoselection. 12. Double Stereodifferentiation with Mutual Kinetic Resolution. A Superior Class of Reagents for Control of Cram's Rule Stereoselection in Synthesis of erythro-α-Alkyl-β-hydroxy Carboxylic Acids from Chiral Aldehydes
-
Chiral α- ketones 7-9 have been prepared and their aldol condesations studied.Compound 8 shows from good to excellent inherent diastereoface selectivity in reactions with achiral aldehydes.Stereoselectivity is related to the size of the alkyl group attached to the aldehyde carbonyl; highest selectivity is observed with diphenylacetaldehyde (>10:1) and pivaldehyde (>19:1).Ketone 8 also shows high diastereoface selectivity in its reactions with chiral, racemic aldehydes 21, 25, 29, and 17, only one stereoisomeric aldol being obtained in each case.Furthermore, the four aforementioned aldehydes show much higher diastereoface selectivity with ketone 8 than they do with the related ketone 1.As a result, the reactions of racemic 8 with these chiral, racemic aldehydes show a high degree of "mutual kinetic resolution".In fact, the rate of the (R)-enolate plus (R)-aldehyde condensation is at least 35 times the rate of the (R)-enolate plus (S)-aldehyde condensation.It is shown by simple logical argument that such mutual kinetic resolution is expected in reactions between two chiral racemic compounds and that the magnitude of the effect should be proportional to the inherent diastereoselectivity shown by each compound in its reaction with achiral reaction partners.Thus, reagents such as 8 can be used to obtain the benefits of double stereodifferentiation even in the racemic form.As an application of the chemistry developed, (+/-)-blastmycinone (47) has been prepared in four steps from ketone 9 (20percent overall yield).
- Heathcock, Clayton H.,Pirrung, Michael C.,Lampe, John,Buse, Charles T.,Young, Steven D.
-
p. 2290 - 2300
(2007/10/02)
-
- Acyclic Stereoselection. 9. Stereochemistry of the Addition of Lithium Enolates to α-Alkoxy Aldehydes
-
The stereochemistry of addition of lithium enolates derived from esters and ketones to the α-alkoxy aldehydes 1-5 has been investigated.In all cases, the predominant product is that predicted by application of Felkin's model for asymmetric induction and by assuming the alkoxy group to be the "large" group.The Cram cyclic model for asymmetric induction is not followed.Stereostructures have been assigned by a combination of conversion to products of known stereostructure, 13C and 1H NMR correlations, and single-crystal X-ray analysis.
- Heathcock, Clayton H.,Young, Steven D.,Hagen, James P.,Pirrung, Michael C.,White, Charles T.,VanDerveer, Don
-
p. 3846 - 3856
(2007/10/02)
-