- Preparation method for synthesizing key intermediate 4-BMA of 1beta-methyl carbapenem antibiotic bicyclic nucleus
-
The invention relates to a preparation method for synthesizing a key intermediate 4-BMA of 1beta-methyl carbapenem antibiotic bicyclic nucleus and belongs to the technical field of synthesis of carbapenem antibiotics. The method disclosed by the invention comprises the following steps: taking an aqueous solution of tetrahydrofuran as a solvent, taking indium as a catalyst, taking (3R,4R)4-carbethoxy-3-[(R)-((tert-butyldimethylsilyl)oxy)ethyl]-2-2-azetidinone (IV) as a raw material, and carrying out a reaction with alpha-bromo-acrylamide XV with large inductive groups so as to produce a compound XIV; not separating the reaction solution of the compound XIV, and performing oxidation-hydrolysis, thereby obtaining the target product VI. The method disclosed by the invention is stable in process, short in reaction route, simple and convenient in operation, mild in reaction conditions, high in product purity, few in three wastes, low in cost, high in yield and suitable for large-scale industrial production.
- -
-
Paragraph 0027; 0035-0037; 0044-0046
(2017/08/29)
-
- Preparation method of meropenem intermediate 4-BMA
-
The invention provides a preparation method of a meropenem intermediate 4-BMA. Low-reaction-activity propionyl spirobenzoxazine cyclohexane is adopted, the meropenem intermediate 4-BMA is prepared through Reformatsky reaction and hydrolysis reaction in sequence, and in the preparation process, side reactions participating in reaction are few, further obtained product impurities are less, and the prepared 4-BMA is high in purity. In addition, the propionyl spirobenzoxazine cyclohexane is adopted as a raw material, the reaction yield is not affected, on the contrary, the reaction yield is greatly improved, and high reaction yield is obtained. Further, the adopted synthetic process is simple, post-treatment is convenient and easy to operate, the raw material and a catalyst are cheap and easy to obtain, safe and environmentally friendly, and the preparation cost is low. An experimental result shows that the mole yield of the prepared meropenem intermediate 4-BMA is 90.0% or above, and the purity is 98.5% or above.
- -
-
Paragraph 0085; 0086; 0087; 0088; 0089; 0090; 0091-0123
(2017/03/18)
-
- 1,3 IMIDAZOLIDINE DERIVATIVES AND THEIR USE IN THE PRODUCTION OF CARBAPENEM
-
Preparation of new heterocyclic compounds characterised by 1,3-imidazolidine structure useful for stereoselective synthesis of optically pure key intermediates in 1β-methylcarbapenem production
- -
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Page/Page column 6
(2011/02/18)
-
- Method for manufacturing stereoselective preparation of 4-BMA using a chiral auxiliary and chiral auxiliary
-
The present invention relates to a process for preparing (3R,4S)-3-[[[R]-1′-t-butyldimethylsilyloxy]ethyl]-4-[(R)-1″-carboxyethyl]-2-azetidinone (beta-methylazetidin-2-one; 4-BMA), a key intermediate for the synthesis of carbapenem and penem antibiotics. Specifically, the present invention relates to a process comprising first, the preparation of a chiral auxiliary from cheap L-Phenylalaninol, and then the preparation of 4-BMA in high yield and high selectivity, under industrially mild condition.
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Page/Page column 3
(2011/06/26)
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- Method for manufacturing stereoselective preparation of 4-bma using a chiral auxiliary and chiral auxiliary
-
The present invention relates to a process for preparing (3R,4S)-3-[[[R]-1 ' -t-butyldimethylsilyloxy ]ethyl]-4-[(R)-1 "-carboxyethyl]-2-azetidinone (beta- methylazetidin-2-one; 4-BMA), a key intermediate for the synthesis of carbapenem and penem antibiotics. Specifically, the present invention relates to a process comprising first, the preparation of a chiral auxiliary from cheap L-Phenylalaninol, and then the preparation of 4-BMA in high yield and high selectivity, under industrially mild condition.
- -
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Page/Page column 5; 9
(2011/08/04)
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- 1,3 IMIDAZOLIDINE DERIVATIVES AND THEIR USE IN THE PRODUCTION OF CARBAPENEM
-
Preparation of new heterocyclic compounds characterised by 1,3-imidazolidine structure useful for stereoselective synthesis of optically pure key intermediates in 1β-methylcarbapenem production
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Page/Page column 15
(2010/05/14)
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- IMPROVED METHOD FOR CRYSTALLIZATION OF AZETIDINONECARBOXYLIC ACID
-
The present invention relates to a method for crystallization of (2R)-2-{(3S,4S)-3-[(1R)-1-(tert-butyldimethylsilyloxy) ethyl]-2-oxoazetidin-4-yl}propionic acid, and is characterized in that crystallization is carried out by mixing a solution containing the compound with a substituted aromatic hydrocarbon solvent and/or a halogenated hydrocarbon solvent. The method can provide a crystal of the compound with a high purity and a high yield while the content of 2S isomer is kept at a low level.
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Page/Page column 9
(2009/04/23)
-
- PROCESS FOR STEREOSELECTIVE PREPARATION OF 4-BMA USING A CHIRAL AUXILIARY
-
The present invention relates to a process for preparing (3R,4S)-3-[[[R]-V-t- butyldimethylsilyloxy] ethyl] -4- [(/?)- l"-carboxyethyl]-2-azetidinone [4-BMA: formula (6)], a key intermediate for the synthesis of carbapenem and penem antibiotics. Specifically, the present invention relates to a process comprising first, the preparation of a chiral auxiliary from cheap L-Valinol, and then the preparation of 4-BMA in high yield and high selectivity, under industrially mild conditions.
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Page/Page column 15-16
(2008/12/08)
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- A PROCESS FOR THE PREPARATION OF THE INTERMEDIATE OF Β-METHYL CARBAPENEM
-
A process of preparation of the intermediate of β-methyl carbapenem is disclosed, in which 4-acetylazacyclobutanone as the raw material is firstly reacted with α-bromopropionamide having a big inductive group. Since this reaction is highly stereoselectivity, most of the product is the required parent nucleus of β-methyl carbapenem, a product of β-configuration. Compared with the prior art, the process of the present invention is highly-yielding, cost-effective and can be used for large scale production.
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Page/Page column 13
(2010/11/28)
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- A PROCESS FOR THE PREPARATION OF MEROPENEM
-
The invention relates to a process for the preparation of meropenem, a β-methylcarbopenem. The said process comprises the following steps: preparing the compound of Formula (XI) from the compound of Formula (IV) through three steps "one-pot process"; then condensing the compound of Formula (XI) with the compound of Formula (XX) to form the compound of Formula (XXIV); finally preparing meropenam of Formula (I) from the compound of Formula (XXIV) by deprotection reaction by means of catalyst. The process of the invention is easily to carry out, the product is isolated in high content and yield, and the cost is reduced, thereby overcoming the shortage of the prior art.
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Page/Page column 16-18
(2010/11/28)
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- SYNTHESIS INTERMEDIATE FOR 1β-METHYLCARBAPENEM DERIVATIVE AND METHOD FOR PRODUCING SAME
-
Disclosed is a low-cost method for producing a 1β-methylcarboxylic acid (A) which is an important intermediate for providing a 1β-methylcarbapenem derivative at low cost. Also disclosed is such an intermediate. By compounds represented by the general formulae (I), (II) and (III) below and a method for producing a 1β-methylcarboxylic acid (A) wherein such compounds are used, a 1β-methylcarboxylic acid (A) as an important intermediate of a 1β-methylcarbapenem derivative can be synthesized from a low-cost, natural L-threonine.
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Page/Page column 28-30
(2010/11/26)
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- Stereoselective mannich-like reactions of ester enolates generated on sugar templates: A novel access to a key intermediate for 1β-methylcarbapenem synthesis
-
The Mannich-like reactions of the enolates generated from 2,3-di-O-protected 6-deoxy-4-O-propionyl-α-D-glucopyranosides with (3R,4R)-4-acetoxy-3-((R)-1-(t-butyldimethylsilyloxy)ethyl ]azetidin-2-one were investigated. The corresponding 2,3-di-O-methyl derivative provided the Mannich adduct in good to excellent stereoselectivity. From the major adduct, the azetidin-2-one incorporating an α-methyl acetic acid side chain at the C-4 position with ?-configuration was obtained by alkaline hydrolysis. This product, (3S,4S)-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl 1-4-1(R)-1-carboxyethylJazetidin-2-one, is a useful intermediate for the 1 ?-methylcarbapenem synthesis.
- Sasaki, Daisuke,Sawamoto, Daisuke,Takao, Ken-ichi,Tadano, Kin-ichi,Okue, Masayuki,Ajito, Keiichi
-
p. 103 - 110
(2008/02/13)
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- Development of a scalable process for 1-β-methyl azetidinone: A carbapenem key intermediate
-
An optimized process for the stereoselective synthesis of 1-β-methyl carbapenem key intermediate (3S,4S)-[(R)-1′-((tert-butyldimethylsilyl)oxy) ethyl]-4-[(R)-1-carboxyethyl]-2-azetidinone (1) and (3R,4R)-4-acetoxy-3-[(R)- 1′-((tert-butyldimethylsilyl)oxy)ethyl]-2-azetidinone has been developed employing commercially available chiral 4-phenyl-2-oxazolidinone. This method provides an efficient and cost-effective process with improved selectivity and higher yield.
- Tewari, Neera,Nizar, Hashim,Rai, Bishwa Prakash,Mane, Avinash,Prasad, Mohan
-
p. 827 - 829
(2012/12/26)
-
- A highly diastereoselective synthesis of a 1-β-methylcarbapenem intermediate using titanium enolate of 2′-hydroxypropiophenone
-
A key 1-β-methylcarbapenem intermediate is synthesized from a highly diastereoselective condensation between the titanium enolate of 2′-hydroxypropiophenone with 4-acetoxy-β-lactam followed by ozonolysis of the resulting ketone to the carboxylic acid.
- Lee, You-Sang,Choung, Won-Keun,Kim, Kyoung Hoon,Kang, Tae Won,Ha, Deok-Chan
-
p. 867 - 870
(2007/10/03)
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- Process for the preparation of 4-substituted azetidinone derivatives
-
Disclosed is a process for the preparation of a 4-substituted azetidinone derivative, which comprises reacting an azetidinone derivative and an amide compound in the presence of a magnesium compound such as those represented by the following formulas (II): and (IV): represented by the following formula (III): MgR5R6??(III) wherein R5represents a C1-12alkyl group, a C2-5alkenyl group, a 5- to 8-membered alicyclic group which may be substituted by a lower C1-4alkyl group, a phenyl group which may be substituted by a lower C1-4alkyl group, a lower C1-4alkoxy group or a halogen atom or a benzyl group which may be substituted by a lower C1-4alkyl group, a lower C1-4alkoxy group or a halogen atom, and R6represents a halogen atom, a methanesulfonyloxy group, a benzenesulfonyloxy group, a p-toluenesulfonyloxy group, a trifluoromethanesulfonyloxy group, an acetoxy group which may be substituted by a halogen atom or a cyano group or an OR7group (R7representing a lower C1-4alkyl group, a substituted or unsubstituted phenyl group or a substituted or unsubstituted benzyl group). The process provides an industrially excellent process for the preparation of a 4-substituted azetidinone derivative which permits the selective preparation of an intermediate for the synthesis of a carbapenem antibacterial agent having a desired 1-β′ configuration.
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Page column 30
(2008/06/13)
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- 1β-Methylcarbapenem intermediates via the thiolysis of a Meldrum's precursor
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5-{3-[1-(tert-Butyldimethylsilyloxy)ethyl]-4-oxo-azetidin-2-yl}-2,2,5- trimethyl-[1,3]dioxane-4,6-dione (3) has been submitted to nucleophilic attack with various nucleophiles. Meldrum's moiety transesterification, C4-substitution, β-lactam ring opening and Meldrum's moiety decarboxylation were observed. Reaction of 3 with ethanethiol and dimethylaminopyridine in ethanol quantitatively furnished ethyl 2-{3-[1-(tert-butyldimethylsilyloxy)ethyl]-4-oxo-azetidin-2-yl}- thiopropionate as the 1:1 mixture of β (7a) and α (8a) diastereoisomers.
- Jacopin, Christophe,Laurent, Mathieu,Belmans, Marc,Kemps, Luc,Cérésiat, Marcel,Marchand-Brynaert, Jacqueline
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p. 10383 - 10389
(2007/10/03)
-
- Process development on (3S,4S)-[(R)-1′-((tert-butyldimethylsilyl)oxy)ethyl]-4-[(R)-1- carboxyethyl]-2-azetidinone 1-β-methylcarbapenem key intermediate
-
The process for the stereoselective synthesis of the 1-β-methylcarbapenem key intermediate 2 via the Reformatsky-type reaction employing a dihydro-oxazinone derivative has been developed for large-scale production. The most difficult problem involved in the development was the exothermic nature of the reaction. Change of acidification order avoided the heat release in the hydrolysis of 5 to 2.
- Lu, Xinbo,Xu, Zunle,Yang, Guojun,Fan, Rong
-
p. 186 - 188
(2013/09/07)
-
- 2,3-Dihydro-4H-1,3-oxazin-4-ones, novel auxiliaries for the stereoselective synthesis of 1β-methylcarbapenems
-
Dihydrooxazinones 9, prepared from benzylcyanide in two steps serve as efficient auxiliaries for the stereoselective synthesis of β-methylcarbapenem intermediate 2. Reformatsky-type reactions of 4-acetoxyazetidinone with α-bromopropionyl dihydrooxazinone 10 provided β-methylazetidinones 4 in high diastereoselectivities. The auxiliaries 9 were also easily removed in the Dieckmann cyclization leading to β-methylcarbapenem skeletons. Practical synthesis of β-methylenolphosphates 2 from 4-acetoxyazetidinone 3 was achieved in three steps (61-77% overall yield).
- Pyun,Jeong,Jung,Kim,Lee,Lee,Kim
-
p. 1950 - 1952
(2007/10/03)
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- A practical and stereocontrolled synthesis of a versatile 1β- methylcarbapenem intermediate
-
S[2(Dialkylaminocarbonyl)phenyl](2R)2[(3S,4S)3[(1R)1(tertbutyldimethylsilylox y)ethyl)]2oxo4azetidinyl]thiopropionate (11), useful intermediates for the synthesis of 1β-methylcarbapenems including 1β-methylthienamycin, were prepared in a highly stereoselective manner by the reaction of E-1-(tert- butyldimethyl-silyloxy)-1-[2-(dialkylaminocarbonyl)phenylthio]-1-propene (10) with commercially available (3S,4R)-3-[(1R)-1-(tert- butyldimethylsilyloxy)ethyl]-4-acetoxyazetidin-2-one (6) in the presence of zinc chloride catalyst. The diethylaminocarbonyl derivative (11b) was particularly convenient for practical production because of its highly crystalline nature.
- Oda, Kozo,Yoshida, Akira
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p. 1439 - 1446
(2007/10/03)
-
- 2-Substituted 2,3-dihydro-4H-1,3-benzoxazin-4-ones: Novel auxiliaries for stereoselective synthesis of 1-β-methylcarbapenems
-
The dihydrobenzoxazone 9e, which is easily prepared from salicylamide 11 and cyclohexanone, serves as an efficient auxiliary in the synthesis of the 1-β-methylcarbapenem key intermediate 10. The stereocontrolled Reformatsky-type reactions of the acetoxyazetidinone 2 with the carboximides 6 gave the intermediates 7 with high diastereoselectivities in high chemical yields. The auxiliary 9e also acts as a good leaving guoup in the TMSCl-promoted Dieckmann-type cyclization leading to a 1-β-methylcarbapenem skeleton. By using this auxiliary, 10 was synthesized in 58% overall yield and four steps from 2.
- Kondo,Seki,Kuroda,Yamanaka,Iwasaki
-
p. 2877 - 2884
(2007/10/03)
-
- Highly stereoselective and practical synthesis of a key intermediate for 1-β-methylcarbapenems
-
The sodium enolate generated from N-propionyl-2, 2-diethyl-1, 3- benzoxazinone 2b was allowed to react with acetoxyazetidinone 3 to give an adduct 4b in 87% yield with virtually complete β-selectivity which was transformed by simple hydrolysis into the optically pure azetidinone-4- isopropionic acid derivative 5, a key intermediate of 1-β-methylcarbapenems.
- Yamanaka, Takeshi,Seki, Masahiko,Kuroda, Tooru,Ohmizu, Hiroshi,Iwasaki, Tameo
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p. 4967 - 4968
(2007/10/03)
-
- Efficient synthesis of 1β-methylcarbapenems based on the counter-attack strategy
-
A seven-step efficient synthesis of 1β-methylcarbapenems 1 from the acetoxyazetidinone 6 is described. The Reformatsky reaction of 3-(2-bromopropionyl)-1,3-benzoxazinone 7 with compound 6 gave an adduct 8 in 96% yield with high β-selectivity (β:α = 92:8). Compound 8 was transformed in three steps into the side-chain thiol esters 12a-e in good yields. The chlorotrimethylsilane-mediated Dieckmann-type cyclisation of thioesters 12b-e followed by counter-attack of the liberated thiolate anion 18 yielded the C-2 alkylthio- or arylthio-substituted 1β-methylcarbapenems 19b-e in a one-pot procedure. The synthesis of 1β-methylcarbapenems 1 was demonstrated by a simple cleavage of the silyl ether and allyl ester of compound 19b to afford target compound 1b in high yield.
- Seki, Masahiko,Kondo, Kazuhiko,Iwasaki, Tameo
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p. 2851 - 2856
(2007/10/03)
-
- An asymmetric synthesis of a key intermediate to 1β-methylcarbapenem antibiotics
-
1β-Methylcarbapenem 3 has been enantioselectively synthesized starting from ethoxyethyl ether 8 and methyl (R)-3-iodo-2-methylpropionate via the intramolecular 1,3-dipolar cycloaddition of nitrone 6, in which the requisite chiral centers were settled.
- Kang Sung, Ho
-
p. 6713 - 6716
(2007/10/02)
-
- An Unusual Stereoselective Decarboxylation: A Key Reaction to an Important Intermediate of Carbapenem Antibiotics
-
The dramatic difference in reactivity of the two diastereomeric acid esters 4A and 4B during decarboxylation has been thoroughly investigated.The (R) isomer 4A underwent decarboxylation to provide a 94:6 mixture of 5A and 5B at 80 deg C in 5-6 h.Under the same conditions the (S) isomer 4B did not undergo decarboxylation and with further heating to 120 deg C gave mainly the ring-opened decomposition product 6 along with unidentified decomposition products.A mechanistic rationale for this unusual reactivity profile is provided.
- Choi, Woo-Baeg,Churchill, Hywyn R. O.,Lynch, Joseph E.,Volante, R. P.,Reider, Paul J.,Shinai, Ichiro
-
p. 8367 - 8370
(2007/10/02)
-
- PROCESS FOR SYNTHESIZING 4-SUBSTITUTED AZETIDINONE DERIVATIVE
-
The invention relates to a process for synthesizing a 4-substituted azetidinone derivative represented by the general formula (3) (wherein OR1 represents a protected hydroxyl group; CO2R3 represents an esterified carboxyl group; and X and Y represent each independently alkyl, alkenyl, aralkyl, aryl, alkylthio, alkoxy, heterocycle, acyl, amino, hydrogen or halogen, or alternatively X and Y are combined together to represent cycloalkan-2-on-2-yl) by the reaction of an azetidinone derivative represented by general formula (1) (wherein OR1 is as defined above; and R2 represents alkyl, alkenyl or aryl) with an ester compound represented by general formula (2): (wherein CO2R3, X and Y are each as defined above) in the presence of zinc and copper compounds. The invention relates also to a compound represented by general formula (3) and further to a compound prepared by decarboxylating the compound (3), both being useful as an intermediate for synthesizing antibacterial carbapenem compounds.
- -
-
-
- Copper-assisted substitution reaction for phenylthio group of a 4- phenylthioazetidinone derivative
-
The phenylthio group of 4-phenylthioazetidinone (1) was readily substituted with copper(I) salts of carboxylates, thiocarboxylates, and copper(I) enolates of malonates and β-ketoesters to give synthetic intermediates (3 and 4) for penem and carbapenem antibiotics.
- Shimamoto,Inoue,Yoshida,Tanaka,Nakatsuka,Ishiguro
-
p. 5887 - 5888
(2007/10/02)
-
- A Simple and Highly Diastereoselective Synthesis of A 1β-Methylcarbapenem Key Intermediate by Deallyloxycarbonylation Using Palladium Complexes
-
A simple, highly diastereoselective synthesis of the key 1β-methylcarbapenem intermediate 1 has been accomplished via a palladium catalyzed deallyloxycarbonylation of diallyl malonate derivative 4a which was readily prepared from (3S,4R)-4-acetoxy-3--2-azetidinone 2 in two steps.
- Murayama, Toshiyuki,Yoshida, Akifumi,Kobayashi, Toyohiko,Miura, Takashi
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p. 2271 - 2274
(2007/10/02)
-
- A stereoselective synthesis of a key 1β-methylcarbapenem intermediate via a diastereoselective decarboxylation
-
(3S,4S)-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-4-[(R)-1-carboxyethyl ]-2-azatidinone 7a was prepared from (3R,4R)-4-acetoxy-3-[(R)-1-t-butyldimethylsilyloxy)ethyl]-2-azetidinon e 3 via a sequence involving coupling with 2,2,5-trimethyl-1,3-dioxan-4,6-dione-4, N-silylation, solvolysis of the methylmeldrum's acid moiety and a stereoselective acid catalyzed decarboxylation.
- Choi, Woo-Baeg,Churchill, Hywyn R. O.,Lynch, Joseph E.,Thompson, Andrew S.,Humphrey, Guy R.,Volante,Reider, Paul J.,Shinkai, Ichiro
-
p. 2275 - 2278
(2007/10/02)
-
- β-Lactams. 3. Asymmetric Total Syntheis of New Non-Natural 1β-Methylcarbapenems Exhibiting Strong Antimicrobial Activities and Stability against Human Renal Dehydropeptidase-I
-
Asymmetric synthesis of 11, the precursor to chiral (3R,4R)-3-ethyl>-4-acetoxyazetidin-2-one (3) was achieved by utilizing a highly diastereoselective aldol-type reaction of acetaldehyde and the chiral tin(II) enolate of 5.Similar diastereoselective alkylations of chiral and achiral tin(II) enolates 13a-d with chiral 3 were also performed to obtain the desired alkylated azetidin-2-ones (17a-d).Compounds 17a,b were successfully converted to new, non-natural 1β-methylcarbapenems 1a and 1b, which exhibited strong and wide-ranging antimicrobial activities and excellent stability against human renal dehydropeptidase-I.
- Nagao, Yoshimitsu,Nagase, Yunosuke,Kumagai, Toshio,Matsunaga, Hiroshi,Abe, Takao,et al.
-
p. 4243 - 4249
(2007/10/02)
-
- Synthetic studies of carbapenem and penem antibiotics. III. A synthesis of a key intermediate for 1β-methylcarbapenem
-
We synthesized useful intermediates 5 and 6 for 1β- and 1α-methylcarbapenems from 4-carboxy-3-[(R)-1-hydroxyethyl]-2-azetidinone 4 as a starting material by using stereoselective hydrogenation and hydroboration, respectively. A practical synthetic route from 4 to the (3S,4S)-4-[(R)-1-carboxyethyl]-3-[(R)-1-hydroxyethyl]-2-azetidinone derivative 1, a useful intermediate for the synthesis of 1β-methylcarbapenem antibiotics, was established.
- Sasaki,Matsumura,Yano,Takata,Sunagawa
-
p. 1098 - 1104
(2007/10/02)
-
- Highly stereocontrolled synthesis of the 1β-methylcarbapenem key intermediate by the Reformatsky reaction of 3-(2-bromopropionyl)-2-oxazolidone derivatives with a 4-acetoxy-2-azetidinone
-
The key synthetic intermediate (4) of 1β-methylcarbapenems (1~3) was efficiently synthesized by employing highly stereocontrolled Reformatsky reaction (C4-alkylation) of 3-(2-bromopropionyl)-2-oxazolidone derivatives (6) with (3R,4R)-4-acetoxy-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-2-azetidino ne (5) in the presence of zinc dust followed by removal of 2-oxazolidone moieties. The best diastereoselectivity (β:α = 95:5) could be realized by uses of sterically crowded achiral 2-oxazolidone derivatives such as 4,4-dimethyl-, 4,4,5,5-tetramethyl, and 4,4-dibutyl-5,5-pentamethylene-2-oxazolidone and higher reaction temperatures (refluxing tetrahydrofran). The remarkable diastereoselectivities observed for the Reformatsky reactions could be explained by means of the weakly chelating transition state models.
- Ito,Sasaki,Tamoto,Sunagawa,Terashima
-
p. 2801 - 2820
(2007/10/02)
-
- 3,4-disubstituted-2-azetidinone derivatives and processes for preparation using tin enolates
-
The invention relates to the preparation of 3,4-disubstituted-2-azetidinone compounds of the formula: STR1 in which R1 is hydrogen or amido-protective group, R2 is hydroxy(lower)alkyl or protected hydroxy(lower)alkyl, R3 is lower alkyl, and R4 is 1-(lower)alkyl-1-hydroxy(C2 -C6)alkyl, 1-(lower)alkyl-1-(protected hydroxy)-(C2 -C6)alkyl or 2-thioxothiazolidin-3-yl, useful as an intermediate for the production of antimicrobial agents by reacting a compound a compound of the formula: STR2 in which R5 is acyl, or salts thereof, with a compound of the formula: or salts thereof, in the presence of an enolizating agent selected from the group consisting of stannous(lower)alkylsulfonate and stannous perhalo(lower)alkylsulfonate.
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-
-
- Stereocontrolled approaches to the key intermediate of 1β-methylthienamycin
-
Two stereocontrolled approaches for the advanced intermediate (2) of 1β-methylthienamycin have been described.
- Rama Rao,Gurjar,Khare,Ashok,Deshmukh
-
p. 271 - 274
(2007/10/02)
-
- A New Synthetic Route to the Key Precursor of 1β-Methylcarbapenem Antibiotics from (S)-Methyl 3-Hydroxy-2-methylpropanoate
-
A new synthetic route to the 1β-methylcarbapenem precursor from (S)-methyl 3-hydroxy-2-methylpropanoate has been developed which involves as a key step the chelation-controlled aldol reaction of (S)-3-benzyloxy-2-methylpropanal with ketene trimethylsilyl acetal of ethyl (trimethylsilyl)acetate.
- Shirai, Fumiyuki,Nakai, Takeshi
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p. 445 - 448
(2007/10/02)
-
- A NOVEL SYNTHESIS OF THE 1β-METHYLCARBAPENEM KEY INTERMEDIATE EMPLOYING THE -CYCLOADDITION REACTION OF CHLOROSULFONYL ISOCYANATE WITH A 4H-1,3-DIOXIN DERIVATIVE
-
A highly stereoselective synthetic route to the title compound was explored by featuring the -cycloaddition reaction of chlorosulfonyl isocyanate with the 4H-1,3-dioxin derivative readily obtainable from methyl (R)-3-hydroxybutyrate, the Baeyer-Villinger reaction resulting in novel cleavage of the acetal moiety, and the Reformatsky reaction with sterically crowded 3-(2-bromopropionyl)-2-oxazolidone derivatives.
- Ito, Yoshio,Kobayashi, Yuko,Terashima, Shiro
-
p. 5631 - 5634
(2007/10/02)
-
- A New Approach to the Chiral Synthesis of the 1-β-Methylcarbapenem Key Precursor Using an Achiral Ketone Sn(II) Enolate
-
A highly stereoselective synthesis of the chiral 1-β-methylcarbapenem key precursor has been accomplished by the aldol-type reaction of the chiral 4-acetoxyazetidinone with a tin(II) enolate generated from 2-methyl-2-siloxy-3-pentanone.
- Shirai, Fumiyuki,Nakai, Takeshi
-
p. 5491 - 5492
(2007/10/02)
-
- ACYCLIC STEREOCHEMICAL CONTROL USING HEXACARBONYLDICOBALT STABILIZED PROPARGYL CATIONS. A HIGHLY STEREOSELECTIVE ROUTE TO 1β-METHYLCARBAPENEM PRECURSORS.
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A highly stereoselective route to precursors of 1β-methylcarbapenems is described.Hydride reduction of a hexacarbonyldicobalt stabilized propargyl cation derived from a 4-acyl-2-azetidinone prepared using the Weinreb ketone synthesis proceeds with complete stereochemical control to a 1β-methylcarbapenem precursor bearing an alkynyl unit.The alkyne is readily elaborated to (3S,4R)-3--4--2-azetidin-2-one or hydrogenated and oxidatively cleaved to (3S,4S)-3--4--azetidin-2-one.
- Prasad, J. Siva,Liebeskind, Lanny S.
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p. 1857 - 1860
(2007/10/02)
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- STEREOSELECTIVE SYNTHESIS OF 1-β-METHYLCARBAPENEM
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Stereoselective syntheses of the 1-β-methylcarbapenem intermediates 9B (R=SPh or OCH3) have been accomplished by an aldol-type stereocontrolled reaction and stereoselective catalytic hydrogenation of an olefinic ester.
- Kim, Choung Un,Luh, Bing,,Partyka, Richard A.
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p. 507 - 510
(2007/10/02)
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- A Stereocontrolled Synthesis of an Important Intermediate for the Preparation of 1β-Methylcarbapenem Antibiotics
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A stereocontrolled chiral synthesis of the 1β-methylcarbapenem antibiotic precursor 3b has been accomplished.The factors influencing the stereochemical outcome of the catalytic hydrogenation of the 1-azabicyclooctanes 4 and 12 are presented.
- Fuentes, L. M.,Shinkai, I.,King, A.,Purick, R.,Reamer, R. A.,et al.
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p. 2563 - 2567
(2007/10/02)
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- Asymmetric Hydrogenation of Unsaturated Carboxylic Acids Catalyzed by BINAP-Ruthenium(II) Complexes
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Homogeneous hydrogenation of α,β- or β,γ-unsaturated carboxylic acids in the presence of a catalytic amount of Ru(OCOCH3)2 affords the corresponding saturated products in high enantiomeric excesses and in quantitative yields.The new hydrogenation has been applied to the asymmetric synthesis of (S)-naproxen, a 1β-methylcarbapenem precursor, and some methylated γ- and δ-lactones
- Ohta, Tetsuo,Takaya, Hidemasa,Kitamura, Masato,Nagai, Katsunori,Noyori, Ryoji
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p. 3174 - 3176
(2007/10/02)
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- SIMPLE AND HIGHLY DIASTEREOSELECTIVE SYNTHESIS OF A 1β-METHYLCARBAPENEM KEY INTERMEDIATE INVOLVING DIVALENT TIN ENOLATES
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A simple and diastereoselective synthesis of 1β-methylcarbapenem key intermediate has been accomplished via a novel C-C bond formation at the C-4 position of 4-acetoxyazetidinone 4 involving divalent tin enolates of 3-propanoyl thiazolidine and oxazolidine-2-thiones derivatives.
- Deziel, Robert,Favreau, Denis
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p. 5687 - 5690
(2007/10/02)
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