- A new strategy for the synthesis of carbapenems. A formal total synthesis of (+)-thienamycin
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A new approach to formation of the carbapenem ring system is presented. The key step involves the Lewis acid mediated cyclocondensation of a β-lactam nitrogen and the α-keto ester of a suitably disposed side-chain. The preparation of a known and pivotal intermediadate in the synthesis of thienamycin serves to demonstrate this strategy.
- Feigelson, Gregg B.
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p. 4747 - 4750
(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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- A Novel Ring-Closure Strategy for the Carbapenems: The Total Synthesis of (+)-Thienamycin
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Intramolecular Michael cyclization of an N--4-(3-nitro-2-propenyl)-3-oxoazetidin-2-one available in optically pure form leads to the corresponding carbapenam skeleton.Further elaboration via oxidative cleavage of an exocyclic nitromethylene group gives an advanced intermediate, which was transformed into (+)-thienamycin.The stereochemistry of the Michael cyclization and the pitfalls of protective group chemistry are discussed.
- Hanessian, Stephen,Desilets, Denis,Bennani, Youssef L.
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p. 3098 - 3103
(2007/10/02)
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- AN EFFICIENT CARBAPENEM SYNTHESIS VIA AN INTRAMOLECULAR WITTIG REACTION OF NEW TRIALKOXYPHOSPHORANE-THIOLESTERS
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New trialkoxyphosphorane-thiolesters 10, obtained by reaction of oxalimides 9 with trialkyl phosphite, were efficiently cyclized by an intramolecular Wittig reaction to give carbapenems 11.
- Yoshida, Akira,Tajima, Yawara,Takeda, Noriko,Oida, Sadao
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p. 2793 - 2796
(2007/10/02)
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- A DIRECT TRANSFORMATION OF BICYCLIC KETO ESTERS TO N-FORMIMIDOYL THIENAMYCIN
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A convenient direct transformation of p-nitrobenzyl 6-(1'-hydroxyethyl)-azabicyclo-(3.2.0)heptane-3,7-dione-2-carboxylate to N-formimidoyl thienamycin utilizing the silylated derivative of N-formimidoyl cysteamine is described.
- Shinkai, I.,Reamer, R. A.,Hartner, F. W.,Liu, T.,Sletzinger, M.
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p. 4903 - 4906
(2007/10/02)
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- Inversion of Configuration at C-8 in the Olivanic Acids: Conversion into the Thienamycins and Other Novel Derivatives
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The inversion of stereochemistry at C-8 in the olivanic acids, MM 22383 (7) and MM 22381 (6), is described.The reaction of p-nitrobenzyl (5R,6S)-3--6--7-oxo-1-azabicyclohept-2-ene-2-carboxylate (8) with diethyl azodicarboxylate, triphenylphosphine, and formic acid afforded the 6- derivative (17), which upon alkaline hydrolysis gave the 6- derivative (18).Hydrolysis of the p-nitrobenzyl ester (18) furnished the sodium salt of N-acetyldehydrothienamycin (15), the (8R)-epimer of the olivanic acid MM 22383 (7).The 3-(2-acetamidoethylthio)-analogue, MM 22381 (6), was converted into N-acetylthienamycin (14) by performing a similar series of reactions on its p-nitrobenzyl ester (10).The transformation of the ester (18) to bis-protected thienamycin (22), via the C-3 thiol (21), is also described.Reaction of the olivanic acid esters (8) and (10) with diethyl azodicarboxylate, triphenylphosphine and hydrazoic acid resulted in the formation of the 6- derivatives (27) and (28).Subsequent hydrolysis provided (5R,6R)-3--6--7-oxo-1-azabicyclohept-2-ene-2-carboxylic acid (29) and the 3-(2-acetamidoethylthio)-analogue (30).
- Corbett, David F.,Coulton, Steven,Southgate, Robert
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p. 3011 - 3016
(2007/10/02)
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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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- A facile transformation of bicyclic keto esters to bisprotected (±)-8-epithienamycin via enol activation
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A facile "one-pot" transformation of bicyclic keto ester (2) to bisprotected (±)-8-epithienamycin via enol phosphate activation followed by the addition-elimination reaction of N-protected cysteamine derivative is described.
- Sletzinger,Liu,Reamer,Shinkai
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p. 4221 - 4224
(2007/10/02)
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- Thienamycin Total Synthesis. 3. Total Synthesis of (+/-)-Thienamycin and (+/-)-8-Epithienamycin
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The completion of the total synthesis of (+/-)-8-epithienamycin and (+/-)-thienamycin from azetidinones 3a and 3b using the methodology developed for the synthesis of model compound 4 (see part 2) is described.
- Schmitt, Susan M.,Johnston, David B.R.,Christensen, B.G.
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p. 1142 - 1148
(2007/10/02)
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