- An improved asymmetric total synthesis of (+)-biotin via the enantioselective desymmetrization of a meso-cyclic anhydride mediated by cinchona alkaloid-based sulfonamide
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The highly enantioselective total synthesis of (+)-biotin 1 via the Hoffmann-Roche lactone-thiolactone strategy has been achieved starting from cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid 2 with an overall yield of 35%. Two contiguous stereogenic centers at C-3a and C-6a were established through a rapid cinchona alkaloid-based sulfonamide-mediated enantioselective alcoholysis of meso-cyclic anhydride 3 to afford (4S,5R)-cinnamyl hemiester 4h, the direct precursor to (3aS,6aR)-lactone 5 with high enantioselectivity. A one-pot installation of the 4-carboxybutyl side chain was accomplished by a Fukuyama coupling reaction of (3aS,6aR)-thiolactone 6 with the organozinc reagent prepared from ethyl 5-bromopentanoate.
- Xiong, Fei,Chen, Xu-Xiang,Chen, Fen-Er
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experimental part
p. 665 - 669
(2010/07/17)
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- Synthetic studies on (+)-biotin, Part 11:[1] Application of Cinchona alkaloid-mediated asymmetric alcoholysis of meso-cyclic anhydride in the total synthesis of (+)-biotin
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A practical and asymmetric process for the totalsyn thesis of (+)-biotin (1) has been accomplished starting from cis-1,3-dibenzyl-2-oxoimidazolidine-4,5- dicarboxylic acid (2). This approach features a highly enantioselective alcoholysis of mesocyclic anhydride 3 into (4S,5R)-cinnamylhemiest er 4 mediated by Cinchona alkaloids. Another attractive feature of this synthesis involves the use of recyclable palladium nanoparticles-catalyzed assembly of the 4-carboxybutyl chain at C-4 in (3aS,6aR)-thiolactone 7 employing an improved Fukuyamatype cross-coupling reaction.
- Dai, Hui-Fang,Chen, Wen-Xue,Zhao, Lei,Xiong, Fei,Sheng, Hao,Chen, Fen-Er
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experimental part
p. 1635 - 1641
(2009/07/18)
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- A practical synthesis of (+)-biotin from L-cysteine
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α-Amino aldehyde 4, which is readily derived from L-cysteine through cyclization and elaboration of the carboxy group, was subjected to the Strecker reaction, which, via sodium bisulfite adduct 16, afforded α-amino nitrile 5 with high diastereose-lectivity (syn/anti = 11:1) and in high yield. Amide 6, derived from 5, was converted to thiolactone 8, a key intermediate in the synthesis of (+)-biotin (1), by a novel S,N-carbonyl migration and cyclization reaction. The Fukuyama coupling reaction of 8 with the zinc reagent 21, which has an ester group, in the presence of a heterogeneous Pd/ C catalyst allowed the efficient installation of the 4-carboxybutyl chain to provide 9. Compound 9 was hydrogenated and the protecting groups removed to furnish 1 in 10 steps and in 34 % overall yield from L-cysteine.
- Seki, Masahiko,Hatsuda, Masanori,Mori, Yoshikazu,Yoshida, Shin-Ichi,Yamada, Shin-Ichi,Shimizu, Toshiaki
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p. 6102 - 6110
(2007/10/03)
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- 2-Thiazolidinone: A novel thiol protective surrogate of complete atom efficiency, a practical synthesis of (+)-biotin
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2-Thiazolidinone derivatives were shown to be novel protective surrogates of a thiol group in L-cysteine derivatives. After elaboration at the C-4 substituent, the thiol group was completely liberated by simple heating in DMF whose atom efficiency is 100%. A practical synthesis of (+)-biotin was accomplished by the use of the strategy employing 4-functionalized 2-thiazolidinone derivatives as the intermediates, allowing a synthesis of (+)-biotin in 10 steps and in 31% overall yield. Short steps, high yield, and ease of operation of the present approach would permit the hitherto most efficient access to (+)-biotin.
- Seki, Masahiko,Kimura, Mayumi,Hatsuda, Masanori,Yoshida, Shin-Ichi,Shimizu, Toshiaki
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p. 8905 - 8907
(2007/10/03)
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- Facile synthesis of (+)-biotin via Fukuyama coupling reaction
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Treatment of a thiolactone 2 with a zinc reagent 3 in the presence of PdCl2(PPh3)2 (10 mol%) allowed installation of a C-2 side chain of (+)- biotin in a highly efficient manner, which enabled synthesis of (+)biotin in three steps from 2. (C) 2000 Elsevier Science Ltd.
- Shimizu, Toshiaki,Seki, Masahiko
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p. 5099 - 5101
(2007/10/03)
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