- A novel synthesis of (+)-biotin from L-cysteine
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(+)-Biotin (1) was synthesized in 25% overall yield over 11 steps from L-cysteine. The contiguous asymmetric centers at C-3a and C-6a were formed through a novel and highly stereoselective Lewis base-catalyzed cyanosilylation of α-amino aldehyde 3 to provide anti- O-TMS-cyanohydrin 4 with high stereoselectivity and in high yield (anti/syn = 92:8, 96%). Treatment of 4 with a di-Grignard reagent, 1,4-bis(bromomagnesio)butane, followed by carbon dioxide, efficiently installed the 4-carboxybutyl chain at C-4 to give keto acid 5. The final cyclization to bicyclic compound 7b, a precursor to 1, was realized by a palladium-catalyzed intramolecular allylic amination of cis-allylic carbonate 6b that was elaborated from 5.
- Seki, Masahiko,Mori, Yoshikazu,Hatsuda, Masanori,Yamada, Shin-ichi
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p. 5527 - 5536
(2007/10/03)
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- Novel Enantioselective Syntheses of (+)-Biotin
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Two conceptually attractive enantioselective syntheses of (+)-biotin from L-cysteine are reported based upon an intramolecular 1,3-dipolar cycloaddition of a carbamoyl azide.The first approach (12 steps) involves the following as key-steps: (i) the macrothiolactonization of acid 10b to Z-olefin 14, (ii) the thermolysis of the ene carbamoyl azide 15 in water with direct formation of a mixture of the benzylated derivatives of (+)-biotin 16a and 17a.The second approach (14 steps) involves the following: (i) elimination of bromide 29 to the endocyclic thioenol ether 30, (ii) thermolysis of the ene carbamoyl azide 30 to the exocyclic thioenol ethers 31a and 31b.Both the synthesis of 29 and the final transformation of 31a and 31b into (+)-biotin are based upon literature precedents.
- Deroose, Frederik D.,De Clercq, Pierre J.
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p. 321 - 330
(2007/10/02)
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- A novel enantioselective synthesis of (+)-biotin
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A conceptually attractive enantioselective 12-step synthesis of (+)-biotin from L-cysteine is reported based upon an intramolecular 1,3-dipolar cycloaddition sequence involving as key-steps (i) the macrothiolactonisation of acid 3 to Z-olefin (4), (ii) the thermolysis of the ene carbamoyl azide 5 in water with direct formation of a mixture of the benzylated derivative of (+)-biotin 6a and 6b.
- Deroose, Frederik D.,De Clercq, Pierre J.
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p. 2615 - 2618
(2007/10/02)
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