- β-Lactams. 2. Diastereoselective Alkylative Discrimination of Racemic 3-Substituted 4-Acetoxyazetidin-2-ones and Its Application to the Synthesis of a Chiral Key Intermediate for Carbapenem Syntheses
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Alkylation of rac 3-substituted 4-acetoxyazetidin-2-one 4 with chiral tin(II) enolate 8 derived from 3-acetyl-(4S)-ethyl-1,3-thiazolidine-2-thione (ETT) (7) proceeded in a highly diastereoselective manner to give alkylated products 9, 10, and 11 in 42percent, 20percent, and 9percent yields, respectively, after chromatographic purification.Similar alkylation of rac-5 with 8 gave 16, 17, and 18 in 45percent, 29percent, and 5percent yields, respectively.Compound 9 was readily converted to 33, a chiral key intermediate for the synthesis of carbapenems.Analytical separation of rac-4 was effectively done with an HPLC technique employing a chiral column packed with A(S)MBC.
- Nagao, Yoshimitsu,Nagase, Yunosuke,Kumagai, Toshio,Kuramoto, Yasuhiro,Kobayashi, Shigeaki,et al.
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p. 4238 - 4242
(2007/10/02)
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- Stereoselective reactions. XX. Synthetic studies on optically active β-lactams. III. Stereocontrolled synthesis of chiral intermediate to (+)-thienamycin from D-glucose
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A chiral key intermediate (19a) for the synthesis of (+)-thienamycin was synthesized starting from D-glucose. The enol ether 13, obtained from the ketone 11 by Horner-Wittig reaction, was transformed to the corresponding methyl ester 16 by pyridinium chlorochromate oxidation or by employing the Wacker process. The ester 16 was further converted to the β-lactam 19a, which is a useful chiral precursor to (+)-thienamycin.
- Ikota,Yoshino,Koga
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p. 2201 - 2206
(2007/10/02)
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- Simple and Condensed β-Lactams. Part 9. Elaboration of the 3-(1-Hydroxyethyl) Side Chains of Potential Intermediates of Carbapenem Antibiotics via the 2-Methyl-1,3-dioxolan-2-yl Group
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Deketalization of the trans compounds methyl and ethyl (2RS,3RS)-1-(2,4-dimethoxybenzyl)-3-(2-methyl-1,3-dioxolan-2-yl)-4-oxoazetidine-2-carboxylates 5b and 5c, and of the cis isomer (6b) of the latter leads to 85:15 mixtures of the trans- and cis-compounds methyl (2RS,3RS)- and (2RS,3SR)-3-acetyl-1-(2,4-dimethoxybenzyl)-4-oxoazetidine-2-carboxylate (7a) and (8a), respectively of the corresponding ethyl esters (7b) and (8b).Sodium borohydride reduction of the mixture of the trans- and cis-esters (7b) and (8b) gives a mixture of the 1'-epimeric trans-compounds ethyl(2RS,3RS)-1-(2,4-dimethoxybenzyl)-3--4-oxazetidine-2-carboxylate (9b) and (10b).Similar mixtures of 1'-epimeric compounds of the types (9) and (10), carrying a variety of substituents attached to position 2 of their azetidine rings were obtained by successive deketalization and reduction of the corresponding trans-(5) and cis-(6) compounds or their mixtures, as well as by other methods.Ring closure of a mixture of the pair of the 1'-epimeric trans-compounds p-nitrobenzyl 2-diazo-4--4-oxo-azetidin-2-yl>-3-oxobutanoates (9n) and (10n) gave a mixture of the 1'-epimeric compounds p-nitrobenzyl 6--2,7-dioxo-(3RS,5RS,6SR)-carbapenam-3-carboxylates (11) and (12) which was converted into a mixture (13) of the 1'-epimeric bis-protected thienamycin analogues p-nitrobenzyl 2-(2-formylaminoethylthio)-6--7-oxo-(5RS,6SR)-carbapen-2-em-3-carboxylates.
- Fetter, Jozsef,Lempert, Karoly,Kajtar-Peredy, Maria,Simig, Gyula
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p. 1135 - 1142
(2007/10/02)
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- Chiral Synthesis of the Key Intermediates of (+)- and (-)-Thienamycin
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Synthesis of the optically active β-keto ester 11a, the key intermediate in the preparation of (+)-thienamycin, has been achieved.An enantioselective cycloaddition of the chiral nitrone with benzyl crotonate was employed as a key reaction.
- Kametani, Tetsuji,Nagahara, Takayasu,Honda, Toshio
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p. 2327 - 2331
(2007/10/02)
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- 3-[1-Hydroxyethyl]-4-carboxymethyl-azetidin-2-one
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In a process for the total synthesis of thienamycin from L-aspartic acid via intermediate III: STR1 there is disclosed a process for preparing III via STR2 wherein R is a protecting group.
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- FROM PENICILLIN TO PENEM AND CARBAPENEM. SYNTHESIS OF 2-OXOCARBAPENAM DERIVATIVE
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Previously obtained 4-iodomethylazetidinone derivative (2a) is transformed via the trans-iodopropenylation method into the β-keto ester (8), which is thought to be an important precursor for the synthesis of the carbapenem derivatives.
- Hirai, Koichi,Iwano, Yuji,Fujimoto, Katsumi
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p. 3251 - 3254
(2007/10/02)
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- Process for the preparation of thienamycin and intermediates
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Disclosed is a process for the total synthesis of thienamycin from 4-allylazetidinone (IIIa) via STR1 L-aspartic acid (III): STR2 R=H, blocking group or salt cation.
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- A PRACTICAL SYNTHESIS OF (+/-)-THIENAMYCIN
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An efficient and operationally simply synthesis of (+/-)-thienamycin is described.
- Melillo, D.G.,Shinkai, I.,Liu, T.,Ryan, K.,Sletzinger, M.
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p. 2783 - 2786
(2007/10/02)
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