- Synthesis of phosphonoacetate analogues of the second messenger adenosine 5′-diphosphate ribose (ADPR)
-
Adenosine 5′-diphosphate ribose (ADPR) is an intracellular signalling molecule generated from nicotinamide adenine dinucleotide (NAD+). Synthetic ADPR analogues can shed light on the mechanism of activation of ADPR targets and their downstream effects. Such chemical biology studies, however, are often challenging due to the negatively charged pyrophosphate that is also sensitive to cellular pyrophosphatases. Prior work on an initial ADPR target, the transient receptor potential cation channel TRPM2, showed complete pyrophosphate group replacement to be a step too far in maintaining biological activity. Thus, we designed ADPR analogues with just one of the negatively charged phosphate groups removed, by employing a phosphonoacetate linker. Synthesis of two novel phosphonoacetate ADPR analogues is described via tandem N,N′-dicyclohexylcarbodiimide coupling to phosphonoacetic acid. Neither analogue, however, showed significant agonist or antagonist activity towards TRPM2, underlining the importance of a complete pyrophosphate motif in activation of this particular receptor.
- Baszczyňski, Ond?ej,Watt, Joanna M.,Rozewitz, Monika D.,Fliegert, Ralf,Guse, Andreas H.,Potter, Barry V. L.
-
-
Read Online
- Composition comprising a phenylalanine-chloroquine derivative as an active ingredient for preventing and treating malaria infection
-
The present invention relates to a composition, comprising a phenylalanine-chloroquine derivative compound, represented by a general formula (I), with a novel structure or a pharmacologically acceptable salt as an active ingredient, for treating and preventing malaria. As a result of identification of anti-malaria activity through a search (experiment example 1) for an anti-malaria effect in vitro by using a strain of Plasmodium falciparum and an animal test (experiment example 2) using a mouse infected from malaria with respect to phenylalanine-chloroquine derivative compounds with novel structures, the novel compounds have been identified to have excellent anti-malaria activity. Accordingly, an anti-malaria agent comprising a phenylalanine-chloroquine derivative compound with a novel structure or a pharmacologically acceptable salt as an active ingredient is provided.COPYRIGHT KIPO 2018
- -
-
Paragraph 0090; 0091; 0093; 0156-0158
(2018/07/28)
-
- Composition comprising a chloroquinoline based α,β-unsaturated amide derivative as an active ingredient for preventing and treating malaria infection
-
The present invention relates to an antimalarial agent containing a chloroquine-based andalpha;,andbeta;-unsaturated amide derivative compound having a novel structure as an active component. According to the present invention, an experiment, in order to analyze antimalarial activities of the chloroquine-based andalpha;,andbeta;-unsaturated amide derivative compounds having the novel structure, has been conducted by testing cytotoxicity in the growth of Hela cells and also by measuring inhibitory activities on the growth of P. falciparum strain. Accordingly, the novel compounds have shown excellence in antimalarial activities. Thus, the composition can be useful for pharmaceutical compositions for preventing and treating malaria.COPYRIGHT KIPO 2016
- -
-
Paragraph 0090-0093
(2017/02/28)
-
- Synthetic approach to wortmannilactone C
-
A diastereomer of wortmannilactone C has been synthesized according to a convergent and versatile strategy from tert-butyl 3-hydroxypropanoate and ethyl (R)-3-hydroxybutanoate. The key steps are a Liebeskind cross-coupling and a Horner-Wadsworth-Emmons (HWE) reaction to construct the macrolactone. The stereogenic centers at C9, C11, and C21 were controlled by enantioselective allyltitanations, and the C19 stereocenter was controlled by using a Noyori reduction of an acetylenic ketone.
- Brandt, Damien,Dittoo, Aurlia,Bellosta, Vronique,Cossy, Janine
-
supporting information
p. 816 - 819
(2015/03/18)
-
- Synthesis of orthogonally protected (2S)-2-amino-adipic acid (α-AAA) and (2S,4 R)-2-amino-4-hydroxyadipic acid (Ahad)
-
(2S,4R)-2-Amino-4-hydroxyadipic acid (Ahad) building block 45 was synthesized in 11 steps and 6.5% overall yield from commercially available materials. Key steps in stereocontrol were an asymmetric conjugate addition employing a proline-based catalyst and a syn-selective intramolecular-conjugate addition of an oxygen nucleophile to an α,β-unsaturated ester. To enable incorporation of α-amino-adipic acid (α-AAA) and Ahad into peptides, a truly orthogonal protecting group scheme was developed, encompassing an allyloxycarbonyl (Alloc) carbamate for Nα, a tert-butyl ester for the δ-COOH, an acetol ester for the α-COOH, and a tert- butyldimethylsilyl ether for the γ-hydroxy group of Ahad.
- Yadav, Saroj,Taylor, Carol M.
-
p. 5401 - 5409
(2013/07/26)
-
- The Wittig-Horner reaction for the synthesis of neratinib
-
The Wittig-Horner reaction is a classic method to get alkenes by reaction phosphonates with carbonyl compounds. In this study, it was used for the synthesis of the anticancer drug neratinib. In this method, ethyl diethoxyphosphinylacetate and dimethylaminoacetaldehyde diethylacetal, replacing (E)-4-(dimethylamino)but-2-enoyl acid hydrochloride and oxalyl chloride, were used to synthesize the 6-position side chain of neratinib.
- Gu, Ning,Yang, Jiabin,Wang, Peng,Li, Lushen,Chen, Yang,Ji, Min
-
p. 3105 - 3110
(2013/09/23)
-
- Stereoselective control in the Staudinger reactions involving monosubstituted ketenes with electron acceptor substituents: Experimental investigation and theoretical rationalization
-
The stereoselectivity of the Staudinger reactions involving monosubstituted ketenes with electron acceptor substituents was investigated experimentally by determination of the product stereochemistry and theoretically via DFT calculations. The results indicate that imines preferentially attack the less sterically hindered exo-side of the ketenes to generate zwitterionic intermediates. Subsequently, for cyclic imines, the intermediates undergo a conrotatory ring closure directly to produce β-lactams, while for linear imines, the imine moiety of the intermediates isomerizes to more stable intermediates, which further undergo a conrotatory ring closure to afford trans-β-lactams. The steric hindrance and the isomerization, rather than the torquoelectronic effect, play crucial roles in controlling the stereoselectivity in the practical Staudinger reactions involving monosubstituted ketenes with electron acceptor substituents, although the unaccessible borylketene with a powerful electron acceptor group controls the stereoselectivity torquoelectronically, in theory.
- Qi, Hengzhen,Li, Xinyao,Xu, Jiaxi
-
supporting information; experimental part
p. 2702 - 2714
(2011/05/19)
-
- Z-selective intramolecular horner-wadsworthemmons reaction for the synthesis of macrocyclic lactones
-
(Figure Presented) When the substrates (ArO)2P(O)CH 2CO2...CHO (Ar = Ph, o-tBuPh) were added to a THF solution containing 3 equiv of NaH at 0 °C or Nal DBU at rt over 1-10 h, the intramolecular Horner-Wadsworth-Emmons reaction proceeded efficiently to give the 12-18-membered-ring lactones in 69-93% yields with 89-100% Z selectivity. On the other hand, (EtO)2P(O)CH2CO2-GHO gave the 13-18-membered-ring lactones in 52-82% yields with 89-99% E selectivity using LiCI-DBU in MeCN or THF.
- Ando, Kaori,Narumiya, Kenji,Takada, Hirokazu,Teruya, Taiji
-
scheme or table
p. 1460 - 1463
(2010/06/15)
-
- Synthesis and antibacterial activity of new aryl / alkyl phosphonates via Michaelis-Arbuzov rearrangement
-
Synthesis of new aryl / alkyl phosphonates 3a-j has been accomplished via a Michaelis- Arbuzov-type rearrangement by the reaction of aryl / alkyl halide (1a-j) with triethyl phosphite (2) in dry toluene at reflux temperature. Products 3a-j were characterized by IR, 13C and 31P NMR and their antibacterial activity was evaluated.
- Syam Prasad, Gandavaram,Manjunath, Manubolu,Kishore Kumar Reddy, Kachi Reddy,Sarathi Reddy, Obulam Vijaya,Suresh Reddy, Cirandur
-
p. 128 - 135
(2015/01/08)
-
- Synthesis of α-fluorinated phosphonoacetate derivatives using electrophilic fluorine reagents: Perchloryl fluoride versus 1-chloromethyl-4- fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor)
-
Triethyl fluorophosphonoacetate and triethyl difluorophosphonoacetate are directly synthesized from triethyl phosphonoacetate by treatment with NaH and 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor). Contrary to a recent report [C.J. Hamilton, S.M. Roberts, J. Chem. Soc., Perkin Trans. 1 (1999) 1051-1056], the reaction proceeded in THF without the need for DMF as a co-solvent. This method is more selective and provides greater convenience and safety than fluorination of the same substrate by treatment with t-BuOK and perchloryl fluoride (FClO3) in toluene while offering advantages over a number of previously described methods employing alternative electrophilic fluorinating reagents or other approaches. Either the monofluoro or the difluoro product can be obtained predominantly by adjusting the molar ratio of base and Selectfluor. Triethyl 2-fluoro-2-phosphonopropionate (ethyl 2-(diethoxyphosphinyl)-2-fluoropropanoate) is also more conveniently made from triethyl 2-phosphonopropanoate using NaH/Selectfluor in THF than with FClO3/t-BuOK in toluene. Detailed procedures are given for obtaining the corresponding triacids in quantitative yield from the fluorinated triesters by P,P-silyldealkylation with bromotrimethylsilane followed by one-pot double hydrolysis with H2O, and isolation as stable dicyclohexylammonium (DCHA) or pyridinium (Py) salts. Substitution of EtOH for H2O in the latter procedure provides the CO-ester phosphonic diacids, isolated as DCHA salts, in one step. 1H, 13C, 31P and 19F NMR data are given for the compounds prepared.
- Marma, Mong S.,Khawli, Leslie A.,Harutunian, Vahak,Kashemirov, Boris A.,McKenna, Charles E.
-
p. 1467 - 1475
(2007/10/03)
-
- One-pot homolytic aromatic substitutions/HWE olefinations under microwave conditions for the formation of a small oxindole library
-
(Chemical Equation Presented) An efficient one-pot sequence comprising a homolytic aromatic substitution followed by an ionic Horner Wadsworth-Emmons olefination for the preparation of a small library of α,β-unsaturated oxindoles is presented. Microwave-induced heating is used to conduct these reactions. The homolytic aromatic substitution is mediated by the persistent radical effect.
- Teichert, Antje,Jantos, Katja,Harms, Klaus,Studer, Armido
-
p. 3477 - 3480
(2007/10/03)
-
- DEHALOGENO COMPOUNDS
-
3-(1-Aminocycloalkyl)pyrrolidinyl-substituted-6-dehalodeno(hydrogen-substituted)quinolon carboxylic acid derivatives having specific substitunets as represented by the following formula (I), its salts, and hydrates thereof exhibit a broad and potent antibacterial activity on gram-negative and gram-positive bacteria, in particular, resistant bacteria typified by gram-positive cocci, including MRSA, PRSP and VRE . Thus these compounds are usable as drugs.
- -
-
-
- Fatty acid synthase inhibitors
-
This invention relates to the use of compounds as inhibitors of the fatty acid synthase FabH.
- -
-
-
- Intramolecular monodealkylation during the attempted synthesis of diethylphosphonoacetohydroxamic acid
-
The reaction of diethyl methyl phosphonoacetate (1) with hydroxylamine in NaOH solution resulted in the loss of one of the phosphorus ethyl groups, and yielded monoethylphosphonoaceto-hydroxamic acid (2) as the major product (79%) and diethylphosphonoacetic acid (3) as the minor product (21%). A series of control experiments were carried out to elucidate the sequence of the reactions leading to 2. When the reaction of 1 with NH2OH was carried out in NaHCO3 solution, a transient product 4 was also observed, which slowly transformed to 2. Compound 4 was assigned the structure diethylphos-phonoacetohydroxamic acid. There was no dealkylation observed at the phosphorus when 1 was reacted with methoxylamine or when O-methyl diethylphosphonoacetohydroxamate (7) was placed in alkaline solution. The dealkylation at phosphorus was interpreted in terms of intramolecular nucleophilic catalysis by the hydroxamic OH group attacking the phosphorus in 4, involving cyclic 1, 2,5-oxazaphospholidine intermediates.
- Chen, Ravit,Breuer, Eli
-
-
- A novel three-component butenolide synthesis.
-
[reaction: see text]. 5-Acylamino butenolides can be assembled by a multicomponent reaction (MCR) of isocyanides, glyoxals, and acetophosphonic acid diethylesters, followed by a intramolecular Wittig-type reaction. The reaction can be performed either in one pot or with the isolation of the intermediate Passerini product. This versatile reaction offers three independent inputs displayed in the final product. Applications in combinatorial chemistry and natural product synthesis can be envisioned.
- Beck,Magnin-Lachaux,Herdtweck,Doemling
-
p. 2875 - 2878
(2007/10/03)
-
- Total synthesis of rutamycin B, a macrolide antibiotic from Streptomyces aureofaciens
-
Rutamycin B (2) was synthesized from three principal subunits, spiroketal 75, keto aldehyde 83, and aldehyde 108. First, triol 62 was assembled by Julia coupling of sulfone 56 with aldehyde 58 followed by an acid-catalyzed spiroketalization. The three hydroxyl functions of 62 were successfully differentiated, leading to phosphonate 75. The latter was condensed in a Wadsworth-Emmons reaction with 83, prepared in six steps from (R)-aldehyde 76, to give 92. Coupling of the titanium enolate of 92 with 108 afforded Felkin product 109 with high stereoselectivity in a process that is critically dependent on the presence of the p-methoxybenzyl ether in the aldehyde. Transformation of 109 via aldehyde 116 to vinylboronate 122 was followed by macrocyclization under Suzuki conditions to yield 123. Exhaustive desilylation of the latter yielded rutamycin B.
- White,Hanselmann,Jackson,Porter,Ohba,Tiller,Wang
-
p. 5217 - 5231
(2007/10/03)
-
- Synthesis of (±)-Rosmarinic Acid Methylester
-
Regioselective cleavage of the glycidic ester 3 by BF3/ether to pyruvic acid ester 4 followed by NaBH4 reduction affords the lactic acid derivative 5a which in turn can be acylated by caffeoyl chloride 8c to yield the O-protected rosmarinic acid ester 9a. Alternatively, 9a can be prepared by acylation of 5a with diethylphosphono acetyl chloride (6c) thus generating the Wadsworth-Emmons reagent 7a which is subsequently reacted with the aldehyde 1a. The analogous reaction using the silyl protected educts 7d and 1b failed to give 9d. Finally, 9a is debenzylated by BCl3 furnishing the title compound 10a in fair total yield.
- Reimann,Maas,Pflug
-
p. 995 - 1008
(2007/10/03)
-
- Inhibitors of farnesyl protein transferase
-
Inhibition of farnesyl transferase, which is an enzyme involved in ras oncogene expression, and inhibition of cholesterol biosynthesis, are effected by compounds of the formula STR1 their enantiomers, diastereomers, and pharmaceutically acceptable salts, prodrugs, and solvates, wherein: x is --ONR1 C(O)--, --N(OR1)C(O)--, --NR1 C(O)--, --C(O)NR1 --, --NR1 S(O2)--, --C(O)O--, --OC(O)--, --C(O)--, --O--, --NR1 -- or --(S)q --; Y is --CO2 R2, --SO3 R2 or --P(O) (OR2) (R3); R is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkenylene or aryl; R3 is --(O)t R4 ; R1, R2 and R4 are each independently hydrogen, alkyl, aryl or aralkyl; m and n are each independently 0 or an integer from 1 to 5; p and t are each independently 0 or 1; and q is an integer from 1 to 2.
- -
-
-
- Farnesyl Diphosphate-Based Inhibitors of Ras Farnesyl Protein Transferase
-
The rational design, synthesis, and biological activity of farnesyl diphosphate (FPP)-based inhibitors of the enzyme Ras farnesyl protein transferase (FPT) is described.Compound 3, wherein a β-carboxylic phosphonic acid type pyrophosphate (PP) surrogate is connected to the hydrophobic farnesyl group by an amide linker, was found to be a potent (I50(FPT) = 75 nM) and selective inhibitor of FPT, as evidenced by its inferior activity against squalene synthetase (I50(SS) = 516 μM) and mevalonate kinase (I50(MK) = >200 μM).A systematic structure-activity relationship study involving modifications of the farnesyl group, the amide linker, and the PP surrogate of 3 was undertaken.Both the carboxylic and phosphonic acid groups of the β-carboxylic phosphonic acid PP surrogate are essential for activity, since deletion of either group results in 50-2600-fold loss in activity (6-9, I50 = 4.6-220 μM).The farnesyl group also displays very stringent requirements and does not tolerate one carbon homologation (12, I50 = 17.7 μM), substitution by a dodecyl fragment (14, I50 = 9 μM), or introduction of an extra methyl group at the allylic position (18, I50 = 55 μM).Modifications around the amide linker group of 3 were more forgiving, as evidenced by the activity of N-methyl analog (21, I50 = 0.53 μM), the one carbon atom shorter farnesoic acid-derived retroamide analog (32, I50 = 250 nM), and the exact retroamide analog (49, I50 = 50 nM).FPP analogs such as 3, 32, and 49 are novel, potent, selective, small-sized, nonpeptidic inhibitors of FPT that may find utility as antitumor agents.
- Patel, Dinesh V.,Schmidt, Robert J.,Biller, Scott A.,Gordon, Eric M.,Robinson, Simon S.,Manne, Veeraswamy
-
p. 2906 - 2921
(2007/10/02)
-
- Inhibition of human immunodeficiency virus type 1 replication by phosphonoformate- and phosphonoacetate-2',3'-dideoxy-3'-thiacytidine conjugates
-
The synthesis of potential 'combined prodrugs' where phosphonoformic acid (PFA) or phosphonoacetic acid (PAA) was attached to the 5'-O or N4 position of 2',3'-dideoxy-3'-thiacytidine (BCH-189) is described. The anti-HIV-1 activity of 11 analogues which included carboxylic ester or phosphoric ester linkages of PFA or PAA to BCH-189 was determined in MT-4 cells. Of these compounds, the IC50 of analogues 3, 4, 6, and 7 ranged from 0.2 to 100 μM, while IC50 for BCH-189 in this system was 0.1 μM. In vitro hydrolysis of the various esters or amides in human plasma indicated that these agents were relatively stable in the presence of plasma esterases with t( 1/2 ) values of up to 120 min. Moreover, lipophilicity of these compounds (partition coefficient) was determined in order to establish correlation between lipophilicity and diffusion of BCH-189 analogues into the cells. The active compounds may exert their effects by extracellular or intracellular hydrolysis to the corresponding antiviral agent BCH-189, but intrinsic anti- HIV-1 activity of some of PAA and PFA adducts, themselves, may also be involved.
- Charvet,Camplo,Faury,Graciet,Mourier,Chermann -,Kraus
-
p. 2216 - 2223
(2007/10/02)
-
- Chemoselective Enzymatic Hydrolysis of Aliphatic and Alicyclic Nitriles
-
Mild and selective hydrolysis of aliphatic and alicycic nitriles leading to carboxylic acids and amides was achieved under neutral conditions by an immobilized enzyme preparation from Rhodococcus sp.This method is particularly useful for the transformation of compounds containing other acid- or basesensitive groups.
- Raadt, Anna de,Klempier, Norbert,Faber, Kurt,Griengl, Herfried
-
p. 137 - 140
(2007/10/02)
-
- Cycloaddition Reactions of (Diethylphosphono)ketenes
-
Methyl- and chloro(diethylphosphono)ketenes were found to add to cyclopentadiene or imines in unusual manner in the certain cases.Some chemical conversions and the Horner-Wittig reaction of the cycloadducts were examined.
- Motoyoshiya, Jiro,Hirata, Kozo
-
p. 211 - 214
(2007/10/02)
-
- The Synthesis of Phosphonobaclofen, an Antagonist of Baclofen
-
Phosphonobaclofen 3-amino-2-(4-chlorophenyl)propylphosphonic acid, has been synthesized in five steps from ethyl 3-(4-chlorophenyl)but-2-enoate, and is a specific antagonist of baclofen.The alternative synthetic pathways, involving conjugate addition of phosphite to 2-(4-chlorophenyl)propenenitrile and of cyanide to 2-(4-chlorophenyl)ethylphosphonate ester, failed.Cyanide ion did add efficiently to ethyl 3-(4-chlorophenyl)-2-diethoxyphosphinylprop-2-enoate and hydrogenation followed by hydrolysis of the product gave (2 S, 3 S)- and (2R, 3 R)-4-amino-3-(4-chlorophenyl)-2-phosphonobutanoic acid, which is also undergoing pharmacological evaluation.
- Chiefari, John,Galanopoulos, Speros,Janowski, Wit K.,Kerr, David I. B.,Prager, Rolf H.
-
p. 1511 - 1518
(2007/10/02)
-
- A Facile and General, One-pot Synthesis of 2-Oxoalkane Phosphonates from Diethylphosphonocarboxylic Acid Chlorides and Organometallic Reagents
-
An efficient and general method for the preparation of 2-oxoalkane phosphonates 2 is described.Diethylphosphono-2-alkanoyl chlorides are used to introduce directly the 2-oxophosphonate 1-substituted synthons on Grignard or cuprate reagents.
- Coutrot, Philippe,Ghribi, Abdellaziz
-
p. 661 - 664
(2007/10/02)
-
- DIETHYL-1-MAGNESIUM CHLORIDE METHANEPHOSPHONATE, A NOVEL GRIGNARD REAGENT AND ITS USE IN ORGANIC SYNTHESIS
-
Diethyl-1-magnesium chloride methanephosphonate was obtained by an exchange reaction between diethyliodo methanephosphonate and isopropylmagnesium chloride in THF at -70 deg.C.Reactions of this novel Grignard reagent with various electrophiles are described, and compared with those of the analogous lithium or copper derivatives.Diethyl-1-magnesium chloride methanephosphonate is especially reactive towards phenylselenium halides and halogens.
- Coutrot, P.,Youssefi-Tabrizi, M.,Grison, C.
-
-
- ORGANOPHOSPHORUS COMPOUNDS AS ANTIVIRAL AGENTS
-
The 5'-triphosphates of 2'-5' linked oligoadenylic acids are formed in cells which have been exposed to interferon and may be involved in the antiviral activity of the latter.The lead(II) ion-catalysed oligomerisation of adenosin 5'-phosphorimidazolidate is a convenient route for the preparation of the 5'-phosphates of 2'-5' linked oligoadenylic acids.The latter can readily be converted to the triphosphates or coupled to the 5'-phosphate of nicotinamide nucleoside to give naturally occurring pyrophosphates which may act as reservoirs for the oligoadenylic acids in cells.Pyrophosphate analoques, eg. phophonoacetic and phosphonoformic acids or carbon-substituted methylenebisphosphonic acids are antiviral agents of potential commercial interest as they inhibit the replication of a number of viruses including herpes and influenza.These pyrophosphate analogues do not appear to inhibit virus replication by being incorporated into nucleoside triphosphates which block nucleic acid synthesis.Rather analogues appear to act by forming stable complexes with an essential metal ion (probably zinc) at the active sites of nucleic acid polymerases of viruses.
- Hutchinson, D. W.,Cload, P. A.,Haugh, M. C.
-
p. 285 - 294
(2007/10/02)
-
- Preparation of dialkyl- and diarylphosphonoalkanoic acids and substituted acrylic acids
-
Process for preparing the substituted phosphonoalkanoic acid of the formula STR1 wherein: R1 is alkyl of 1-8 carbon atoms, aralkyl of 7-10 carbon atoms, phenyl, or substituted phenyl of 6-10 carbon atoms; R2 is H, hydrocarbyl of 1-18 carbon atoms, or substituted hydrocarbyl of 1-18 carbon atoms, wherein in said hydrocarbyl groups the carbon atom attached to the STR2 moiety is substituted with two or three hydrogen atoms or is a carbon atom of an aromatic ring; and Y is oxygen or sulfur, which process comprises contacting and reacting, at a temperature of about -70° C. to about 125° C., a pressure of about 1-100 atmospheres (0.1-10 MPa), and for a time sufficient to effect reaction, the phosphite ester of the formula STR3 wherein R1 and Y are as defined above, with the α-halocarboxylic acid of the formula R2 CHXCO2 H, wherein X is Cl, Br, or I and R2 is as defined above, in the presence of at least two moles of base per mole of limiting reagent, said base having a pKa greater than about 15, to produce the substituted phosphonoalkanoic acid, and process for preparing the substituted acrylic acid of the formula R3 R4 C=CR2 COOH wherein: R2 is as defined above; and R3 and R4 are the same or different and are selected from H, hydrocarbyl of 1-18 carbon atoms, and substituted hydrocarbyl of 1-18 carbon atoms or R3 and R4 taken together are cycloalkylene or substituted cycloalkylene of 4-18 carbon atoms, which process comprises: (a) carrying out the aforesaid reaction to produce the substituted phosphonoalkanoic acid except that at least three moles of base are present; and (b) contacting and reacting, at a temperature of about -70° to about 125° C., a pressure of about 1-100 atmospheres (0.1-10 MPa), and for a time sufficient to effect reaction, the substituted phosphonoalkanoic acid produced in step (a) with the carbonyl compound of the formula R3 R4 C=O, wherein R3 and R4 are as defined above, to produce the substituted acrylic acid.
- -
-
-
