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Accession number;03A0096359
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| Title;A Novel and Practical Synthesis of (+)-Biotin via Fukuyama Coupling Reaction. |
| Author;
SHIMIZU TOSHIAKI
(Tanabeseiyaku Seisangiken)
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Journal Title;Journal of the Pharmaceutical Society of Japan
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Journal Code:F0508A
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ISSN:0031-6903
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VOL.123;NO.2;PAGE.43-52(2003)
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| Figure&Table&Reference;FIG.9, TBL.6, REF.46 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;(+)-Biotin (1) was synthesized from readily accessible L-aspartic acid (4). The contiguous asymmetric centers at C-3a and C-6a were formed through a diastereoselective aldol reaction of N-Cbz-3-amino-4-butanolide 5 to provide trans-disubstituted lactone 6 with high stereoselectivity (trans/cis=12:1). The imidazolidin-2-one moiety of 1 was constructed by a stereoselective Hofmann rearrangement of .BETA.-substituted asparagine derivative 7 to provide cyclic urea 8. This reaction proceeds with complete retention of stereochemistry. Removal of the protective groups of 8 and subsequent dibenzylation and thionation provided thiolactone 2. The installation of the C-4 side chain of 1 was performed through a Pd/C-catalyzed coupling reaction of 2 with ethoxycarbonylbutylzinc iodide 14a (Fukuyama coupling reaction), which permitted the synthesis of 1 from 2 under industrially applicable mild conditions in three steps. (author abst.) |
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