- Pyridine derivatives
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The invention relates to a process for producing pyridinoline and deoxypyridinoline crosslinks and derivatives thereof and their use in determining connective tissue disorders in humans and animals.
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- Collagen cross-links: Synthesis of pyridinoline, deoxypyridinoline and their analogues
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An efficient chiral synthesis of (S,S)-(-)-3g, a key intermediate for the preparation of collagen cross-links pyridinoline (Pyd, 1) and deoxypyridinoline (Dpd, 2) was achieved from (4S)-5(tert-butoxy)-4-[(tert- butoxycarbonyl)amino]-5-oxopentanoic acid (21b). Quaternization of (S,S)-(- )-3g with iodide (2S, 5R)-(+)-4a followed by hydrolysiS provided a first chiral synthesis of natural (+)-Pyd (1). 1-(2S)-(+)-Pyd (1) was also synthesized from (S,S)-(-)-3g and iodide (2S, 5S)-(+)-4a. Similarly, quaternization of (S,S)-(-)-3g with iodide (2S)-(-)-4b, which was prepared from (2S)-(-)-6-amino-2[(tert-butoxycarbonyl)amino]hexanoic acid (31) in three steps, followed by hydrolysis afforded natural (+)-Dpd (2) in 5.3% overall yield. Also, the synthesis of racemic Dpd [(±)-2] and a variety of its analogues is presented.
- Adamczyk, Maciej,Johnson, Donald D.,Reddy, Rajarathnam E.
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