Synthesis of 3-Fluoro-Oxetane δ-Amino Acids |
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Authors: | Susana Dias Lucas Amélia Pilar Rauter Josef Schneider Hans Peter Wessel |
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Institution: | 1. Centro de Química e Bioquímica, Departamento de Química e Bioquímica , Faculdade de Ciências da Universidade de Lisboa , Edifício C8, 5° Piso, Campo Grande, 1749-016, Lisboa, Portugal;2. F. Hoffmann-La Roche Ltd., Pharmaceutical Research , CH-4070, Basel, Switzerland |
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Abstract: | Starting from d-xylose, 2,4-anhydro-5-N-(tert-butoxycarbonyl)amino-5-deoxy-3-fluoro-d-arabinonic acid 11 was synthesized over 10 steps including ring contraction, fluorination, and ester hydrolysis. Bromine oxidation of d-xylose followed by benzylidenation in a one-pot procedure led to a ca. 1:1 mixture of lactone 3 and 2,4;3,5-dibenzylidene xylonic acid (4) as by-product. For the synthesis of the d-xylo derivative 24, the chosen starting material was 1,2-O-isopropylidene-α-d-xylofuranose. A total of 14 steps including epimerization, ring contraction, fluorination, and saponification led to the desired fluoro-oxetane δ-amino acid 24. Hydrolysis of the 3-fluoro-oxetane δ-amino esters 10 and 23 by means of LiOH was successful in agreement with the results previously reported for similar 3-methoxy oxetanes, whereas chemical hydrolysis was not possible for 3-hydroxy derivatives. |
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Keywords: | Carbohydrate amino acids δ-Amino acids Oxetanes Carbohydrate scaffolds |
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